<SEC-DOCUMENT>0000874015-21-000056.txt : 20210224
<SEC-HEADER>0000874015-21-000056.hdr.sgml : 20210224
<ACCEPTANCE-DATETIME>20210224153410
ACCESSION NUMBER:		0000874015-21-000056
CONFORMED SUBMISSION TYPE:	10-K
PUBLIC DOCUMENT COUNT:		130
CONFORMED PERIOD OF REPORT:	20201231
FILED AS OF DATE:		20210224
DATE AS OF CHANGE:		20210224

FILER:

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

	FILING VALUES:
		FORM TYPE:		10-K
		SEC ACT:		1934 Act
		SEC FILE NUMBER:	000-19125
		FILM NUMBER:		21672307

	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 12-31-2020
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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>
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<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>
<div style="text-align: center;"><span style="font-size: 8pt; font-family: 'Times New Roman', Times, serif;"> </span><br /></div>
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<div style="text-align: center;"><span style="font-size: 8pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"> </span><br /></div>
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<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(Registrant&#8217;s telephone number, including area code)</div>
<div><br /></div>
<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: left; text-indent: 18pt;"><span style="font-size: 8pt; font-family: 'Times New Roman', Times, serif;"> </span><br /></div>
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Securities registered pursuant to Section 12(g) of the Act: <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">None</span></div>
<table cellpadding="0" cellspacing="0" id="zaca7f24aad584406bf1af4c14a1f6aff" 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: 32.84%; vertical-align: top;">&#160;</td>
    <td style="width: 34.31%; vertical-align: top; border-bottom: #000000 2px solid;">&#160;</td>
    <td style="width: 32.84%; vertical-align: top;">&#160;</td>
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<div><br /></div>
<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Indicate by check mark if the Registrant is a well-known seasoned issuer, as defined in Rule 405 of the Securities Act. <ix:nonNumeric name="dei:EntityWellKnownSeasonedIssuer" id="Fact_8181ec6bd9444560b973abd8ec5edd85" contextRef="c20200101to20201231">Yes</ix:nonNumeric>&#xA0;<span style="font-size: 10pt; font-family: 'Segoe UI Symbol';">&#x2612;&#160; </span>No <span style="font-size: 10pt; font-family: 'Segoe UI Symbol';">&#x2610;</span></div>
<div style="text-align: justify; text-indent: 18pt;"><span style="font-size: 8pt; font-family: 'Times New Roman', Times, serif;"> </span><br /></div>
<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Indicate by check if the Registrant is not required to file reports pursuant to Section 13 or Section 15(d) of the Act. Yes <span style="font-size: 10pt; font-family: 'Segoe UI Symbol';">&#x2610;&#160; </span><span style="font-size: 10pt; font-family: 'Segoe UI Symbol';"><ix:nonNumeric name="dei:EntityVoluntaryFilers" id="Fact_7442cd141d5b49d28fa5f051e62f0f9a" contextRef="c20200101to20201231">No</ix:nonNumeric></span>&#xA0;<span style="font-size: 10pt; font-family: 'Segoe UI Symbol';">&#x2612;</span></div>
<div style="text-align: justify; text-indent: 18pt;"><span style="font-size: 8pt; font-family: 'Times New Roman', Times, serif;"> </span><br /></div>
<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Indicate by check mark whether the Registrant (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_12d59d6472a241a6ba2f33570a36695c" contextRef="c20200101to20201231">Yes</ix:nonNumeric>&#xA0;<span style="font-size: 10pt; font-family: 'Segoe UI Symbol';">&#x2612;&#160; </span>No <span style="font-size: 10pt; font-family: 'Segoe UI Symbol';">&#x2610;</span></div>
<div style="text-align: justify; text-indent: 18pt;"><span style="font-size: 8pt; font-family: 'Times New Roman', Times, serif;"> </span><br /></div>
<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Indicate by check mark whether the registrant has submitted electronically every Interactive Data File required to be submitted pursuant to Rule 405 of Regulation S-T (&#167;232.405 of this chapter) during the preceding 12 months (or for such shorter period that the registrant was required to submit such files). <ix:nonNumeric name="dei:EntityInteractiveDataCurrent" id="Fact_bc8e812a78494703b8ebe0d0e51c10b9" contextRef="c20200101to20201231">Yes</ix:nonNumeric>&#xA0;<span style="font-size: 10pt; font-family: 'Segoe UI Symbol';">&#x2612;&#160; </span>No <span style="font-size: 10pt; font-family: 'Segoe UI Symbol';">&#x2610;</span></div>
<div style="text-align: left; text-indent: 18pt;"><span style="font-size: 8pt; font-family: 'Times New Roman', Times, serif;"> </span><br /></div>
<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Indicate by check mark whether the registrant is a large accelerated filer, an accelerated filer, a non-accelerated filer, a smaller reporting company, or an emerging growth company. See the definitions of &#8220;large accelerated filer,&#8221; &#8220;accelerated filer,&#8221; &#8220;smaller reporting company,&#8221; and &#8220;emerging growth company&#8221; in Rule 12b-2 of the Exchange Act.</div>
<div style="text-align: center;"><span style="font-size: 8pt; font-family: 'Times New Roman', Times, serif;"> </span><br /></div>
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    <td style="width: 48.93%; vertical-align: top;">&#160;</td>
    <td style="width: 2.14%; vertical-align: bottom;">&#160;</td>
    <td style="width: 48.93%; vertical-align: top;">&#160;</td>
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    <td style="width: 2.14%; vertical-align: bottom;">&#160;</td>
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    <td style="width: 48.93%; vertical-align: top;">&#160;</td>
    <td style="width: 2.14%; vertical-align: bottom;">&#160;</td>
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<div style="text-align: center;"><span style="font-size: 8pt; font-family: 'Times New Roman', Times, serif;"> </span><br /></div>
<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Securities Act. </span><span style="font-size: 10pt; font-family: 'Segoe UI Symbol';">&#x2610;</span></div>
<div><br /></div>
<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Indicate by check mark whether the registrant has filed a report on and attestation to its management assessment of the effectiveness of its internal controls over financial reporting under Section 4049b) of the Sarbanes-Oxley Act (15 U.S.C. 7262(b)) by the registered public accounting firm that prepared or issued its audit report <span style="font-size: 10pt; font-family: 'Segoe UI Symbol';">&#x2612;</span></div>
<div><br /></div>
<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Indicate by check mark whether the Registrant is a shell company (as defined in Rule 12b-2 of the Act). Yes </span><span style="font-size: 10pt; font-family: 'Segoe UI Symbol';"><ix:nonNumeric name="dei:EntityShellCompany" id="Fact_1d0d0c8710834efab1a954dc120430bc" contextRef="c20200101to20201231" format="ixt-sec:boolballotbox">&#x2610;</ix:nonNumeric></span><span style="font-size: 12pt; font-family: 'Segoe UI Symbol';">&#160; </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">No </span><span style="font-size: 10pt; font-family: 'Segoe UI Symbol';">&#x2612;</span></div>
<div style="text-align: left; text-indent: 18pt;"><span style="font-size: 8pt; font-family: 'Times New Roman', Times, serif;"> </span><br /></div>
<div style="text-align: 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_75efd54aaa5949eea6a47fd75948207f" contextRef="c20200630" unitRef="U001" decimals="0" scale="0" format="ixt:numdotdecimal">6,748,320,336</ix:nonFraction> as of June 30, 2020.*</div>
<div style="text-align: left; text-indent: 18pt;"><span style="font-size: 8pt; font-family: 'Times New Roman', Times, serif;"> </span><br /></div>
<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The number of shares of voting common stock outstanding as of February 18, 2021 was <ix:nonFraction name="dei:EntityCommonStockSharesOutstanding" id="Fact_0e9ab674d7554251b88aaff73a0fa9b4" contextRef="c20210218" unitRef="U002" decimals="INF" scale="0" format="ixt:numdotdecimal">140,862,211</ix:nonFraction>.</div>
<div><br /></div>
<div style="text-align: center; text-indent: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">DOCUMENTS INCORPORATED BY REFERENCE</div>
<div><br /></div>
<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Portions of the Registrant&#8217;s definitive Proxy Statement to be filed on or about April 23, 2021 with the Securities and Exchange Commission in connection with the Registrant&#8217;s annual meeting of stockholders to be held on June 2, 2021 are incorporated by reference into Part III of this Report.</div>
<div style="text-align: left; text-indent: 18pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> </span><br /></div>
<table cellpadding="0" cellspacing="0" id="z1a875124529e4494853e3227356010a7" 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: 30.71%; vertical-align: top; border-bottom: #000000 2px solid;">&#160;</td>
    <td style="width: 69.29%; vertical-align: top;">&#160;</td>
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    <td style="width: 18pt; vertical-align: top; align: right; 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 25,033,497 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, 2020. 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 style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">FORWARD-LOOKING STATEMENTS</div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><!--PROfilePageNumberReset%Num%2%%%--></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">This report on Form 10-K and the information incorporated herein by reference includes forward-looking statements regarding our business and the therapeutic and commercial potential of SPINRAZA (nusinersen), TEGSEDI (inotersen), WAYLIVRA (volanesorsen) and our technologies and products in development, including the business of Akcea Therapeutics, Inc., our wholly owned subsidiary. 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, including those related to the impact of COVID-19 could have on our business, and particularly those inherent in the process of discovering, developing and commercializing medicines that are safe and effective for use as human therapeutics, and in the endeavor of building a business around such medicines. Our forward-looking statements also involve assumptions that, if they never materialize or prove correct, could cause our results to differ materially from those expressed or implied by such forward-looking statements. Factors that could cause or contribute to such differences include, but are not limited to, those discussed in this report on Form 10-K, including those identified in Item 1A entitled &#8220;Risk Factors&#8221;. Although our forward-looking statements reflect the good faith judgment of our management, these statements are based only on facts and factors currently known by us. As a result, you are cautioned not to rely on these forward-looking statements.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In this report, unless the context requires otherwise, &#8220;Ionis,&#8221; &#8220;Company,&#8221; &#8220;we,&#8221; &#8220;our,&#8221; and &#8220;us&#8221; refers to Ionis Pharmaceuticals, Inc. and its subsidiaries.</div>
<div><br /></div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Summary of Risk Factors</div>
<div><br /></div>
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">There are a number of risks related to our business and our securities. Below is a summary of material factors that make an investment in our securities speculative or risky. Importantly, this summary does not address all of the risks that we face. Additional discussion of the risks summarized in this risk factor summary, as well as other risks that we face, can be found in this report on Form 10-K in Item 1A entitled &#8220;Risk Factors.&#8221;:</div>
<div style="text-align: left;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"> </span><br /></div>
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    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; 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 impact on our operations and financial condition from the effects of the current COVID-19 pandemic;</div></td>
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    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; 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 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="z15d99ddaa7f744968c7a5e6404675617">
  <tr>
    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; 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 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="zc12de9854cd64a2f9bde9f72dc774a84">
  <tr>
    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">the availability of adequate coverage and payment rates for our medicines;</div></td>
  </tr>
</table>
<table 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="zba885b92b5dc454190c1ffdd83b68d2e">
  <tr>
    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">our ability to successfully manufacture our medicines;</div></td>
  </tr>
</table>
<table 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="z12dcad1d0c2c477c85bbe9c2f60bdcf5">
  <tr>
    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">our ability to successfully develop and obtain marketing approvals for our medicines;</div></td>
  </tr>
</table>
<table 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="z7d1a0d8434044934861666137257af83">
  <tr>
    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">our ability to secure and maintain effective corporate partnerships;</div></td>
  </tr>
</table>
<table 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="z87b0f9e75df44f2b8fa688a286cf9313">
  <tr>
    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">our ability to sustain cash flows and achieve consistent profitability;</div></td>
  </tr>
</table>
<table 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="z74177bebc51c4bc9a63faedbbb589ee4">
  <tr>
    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; 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; and</div></td>
  </tr>
</table>
<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="zc05da0ca7c8b4c569b7ee97a4c6cafff">
  <tr>
    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; 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.</div></td>
  </tr>
</table>
<div><br /></div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">TRADEMARKS</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">&#160;</span>&#8220;Ionis,&#8221; the Ionis logo, and other trademarks or service marks of Ionis Pharmaceuticals, Inc. appearing in this report are the property of Ionis Pharmaceuticals, Inc. &#8220;Akcea,&#8221; the Akcea logo, and other trademarks or service marks of Akcea Therapeutics, Inc. appearing in this report are the property of Akcea Therapeutics, Inc, Ionis&#8217; wholly owned subsidiary. This report contains additional trade names, trademarks and service marks of others, which are the property of their respective owners. Solely for convenience, trademarks and trade names referred to in this report may appear without the &#174; or TM symbols.</div>
<div><br /></div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">CORPORATE INFORMATION</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We incorporated in California in 1989 and in January 1991 we changed our state of incorporation to Delaware. In December 2015, we changed our name to Ionis Pharmaceuticals, Inc. from Isis Pharmaceuticals, Inc. Our principal offices are in Carlsbad, California. In December 2014, we formed Akcea Therapeutics, Inc., as a Delaware corporation, with its principal office in Boston, Massachusetts. Prior to Akcea&#8217;s initial public offering, or IPO, in July 2017, we owned 100 percent of Akcea&#8217;s stock. In October 2020, we acquired the remaining shares of Akcea.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We make available, free of charge, on our website, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">www.ionispharma.com</span>, our reports on Forms 10-K, 10-Q, 8-K and amendments thereto, as soon as reasonably practical after we file such materials with the Securities and Exchange Commission. 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.</div>
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<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span>2</span></div>
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<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">IONIS PHARMACEUTICALS, INC.</div>
<div 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, 2020</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 /></div>
<table cellpadding="0" cellspacing="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" id="z46603b9f44154f32bc9a45d8fcf4c31e">
  <tr>
    <td style="width: 10.51%; vertical-align: top;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">PART I</div></td>
    <td style="width: 83.22%; vertical-align: top;">&#160;</td>
    <td style="width: 6.27%; vertical-align: top;">&#160;</td>
  </tr>
  <tr>
    <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>
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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;">Business</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;">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;">Risk Factors</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;">47</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;">Unresolved Staff Comments</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;">63</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 2.</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;">Properties</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;">63</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 3.</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;">Legal Proceedings</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;">64</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 4.</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;">Mine Safety Disclosures</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;">64</div></td>
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  <tr>
    <td style="width: 10.51%; vertical-align: top; background-color: #CCEEFF;">&#160;</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;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">PART II</div></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;">&#160;</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;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Item 5.</div></td>
    <td style="width: 83.22%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Market for Registrant&#8217;s Common Equity, Related Stockholder Matters and Issuer Purchases of Equity Securities</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;">64</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 6.</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;">Selected Financial Data</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 7.</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;">Management&#8217;s Discussion and Analysis of Financial Condition and Results of Operations</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>
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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 7A.</div></td>
    <td style="width: 83.22%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Quantitative and Qualitative Disclosures About Market Risk</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;">78</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 8.</div></td>
    <td style="width: 83.22%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Financial Statements and Supplementary Data</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 9.</div></td>
    <td style="width: 83.22%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Changes in and Disagreements With Accountants on Accounting and Financial Disclosure</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>
  </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 9A.</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;">Controls and Procedures</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 9B.</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;">Other Information</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>
  </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; font-weight: bold;">PART III</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>
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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;">Directors, Executive Officers and Corporate Governance</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;">81</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;">Executive Compensation</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;">81</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;">Security Ownership of Certain Beneficial Owners and Management and Related Stockholder Matters</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;">81</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;">Certain Relationships and Related Transactions, and Director Independence</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 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;">Principal Accounting Fees and Services</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: 83.22%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Exhibits, Financial Statement Schedules</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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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">PART I</div>
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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Item 1. Business</div>
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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Overview</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 a leader in RNA-targeted therapy and believe our medicines are pioneering new markets, changing standards of care and transforming the lives of people with devastating diseases. Our clinical pipeline of potential first-in-class and/or best-in-class medicines <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">address a broad range of diseases. We are primarily focused on two core franchises: neurology and cardiometabolic. </span>Our commercial products SPINRAZA, TEGSEDI and WAYLIVRA, are approved in major markets around the world. Within our late-stage pipeline, we have six Phase 3 studies underway with five medicines: tofersen for SOD1-ALS, tominersen for Huntington&#8217;s disease, IONIS-TTR-L<sub>Rx</sub> for transthyretin, or TTR,<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> amyloidosis</span>, IONIS-APOCIII-L<sub>Rx</sub> for familial chylomicronemia syndrome, or FCS, and pelacarsen for lipoprotein(a), or 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;">2020 was a transformational year for Ionis. With new leadership and a new strategy to commercialize medicines from our wholly owned pipeline, we took important steps towards our goal of becoming one of the most successful biotechnology companies. We invested in our commercial capabilities and expanded our wholly owned pipeline, accelerated by the acquisition of Akcea Therapeutics, or the Akcea Acquisition. As one company, we believe we are stronger and more efficient, with enhanced ability to achieve even greater future success. We initiated two Phase 3 studies and reported clinical proof-of-concept results from six medicines. We also advanced our mid-stage pipeline by initiating more than ten Phase 2 studies, including four studies with our wholly owned medicines. In 2020, we also broadened the scope of our technology by demonstrating we could safely and effectively deliver an antisense medicine to the lungs. We accomplished all this and achieved our 2020 financial guidance, with <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">revenues of $729.3 million and a year-end cash balance of $1.9 billion,</span> even in the challenging COVID-19 pandemic environment.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#160;Our multiple sources of revenue provide us with substantial financial strength. Our financial strength enables us to execute on our capital allocation strategy, which is focused on internal investment in three key areas: our wholly owned pipeline, building our commercial capabilities and broadening the reach of our technology. We believe investing in these areas moves us closer to our goal of 12 or more marketed products in 2026 and will drive the greatest value for patients and shareholders.</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;">Commercial Medicines</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">SPINRAZA is the global foundation-of-care for the treatment of patients of all ages with spinal muscular atrophy, or SMA, a progressive, debilitating and often fatal genetic disease. Biogen, our partner responsible for commercializing SPINRAZA worldwide, reported that as of December 31, 2020, over 11,000 patients were on SPINRAZA therapy in markets around the world. SPINRAZA is approved in over 50 countries with formal reimbursement in over 40 countries. From inception through December 31, 2020, we have earned $1.3 billion in revenues from our SPINRAZA collaboration, including more than $930 million in royalties on sales of SPINRAZA.</div>
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<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 polyneuropathy caused by hereditary TTR amyloidosis, or hATTR, a debilitating, progressive, and fatal disease. As of December 31, 2020, TEGSEDI was commercially available in 15 countries. In 2021, we began selling TEGSEDI in Europe through a distribution model with Swedish Orphan Biovitrum AB, or Sobi. In Latin America, PTC Therapeutics International Limited, or PTC, through its exclusive license agreement with us, is commercializing TEGSEDI in Brazil and is working towards access in additional Latin American countries.</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;">WAYLIVRA is a once weekly, self-administered, </span>subcutaneous medicine that<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> received conditional marketing authorization in May 2019 from the European Commission, or EC, as an adjunct to diet in adult patients with genetically confirmed FCS and at high risk for pancreatitis. We launched WAYLIVRA in the EU in the third quarter of 2019. In 2021, we began selling WAYLIVRA through a distributor, Sobi. Through our exclusive license agreement with PTC, we are working to expand access to WAYLIVRA across Latin America, beginning in Brazil. In the second quarter of 2020, PTC submitted the WAYLIVRA marketing application for approval in Brazil to </span>the National Health Surveillance Agency (Ag&#234;ncia Nacional de Vigil&#226;ncia Sanit&#225;ria), or <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">ANVISA.</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;">Medicines in Phase 3 Studies</div>
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<div style="text-align: left; text-indent: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We advanced our pipeline of medicines that we believe will pioneer new markets and change standards of care. Our Phase 3 medicines include:</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;">Tofersen: Biogen completed enrollment in the VALOR Phase 3 study in patients with SOD1-ALS in December 2020</div></td>
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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;">Tominersen: Roche completed enrollment of the GENERATION HD1 Phase 3 study for tominersen in April 2020</div></td>
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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;">IONIS-TTR-L<sub>Rx</sub>: Enrollment ongoing in both the NEURO-TTRansform and the CARDIO-TTRansform Phase 3 studies</div></td>
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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;">IONIS-APOCIII-L<sub>Rx</sub>: We initiated the BALANCE Phase 3 study in patients with FCS in December 2020</div></td>
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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;">Pelacarsen: Novartis began enrollment in the Lp(a)HORIZON Phase 3 cardiovascular outcome study and the U.S. Food and Drug Administration, or FDA, granted pelacarsen Fast Track Designation as a potential treatment for people at significant risk for cardiovascular disease due to elevated levels of Lp(a).</div></td>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">COVID-19</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">As a company focused on improving the health of people around the world, our priority during the COVID-19 pandemic is the safety of our employees, their families, the healthcare workers who work with us and the patients who rely on our medicines. We are also focused on maintaining the quality of our studies and minimizing the impact to timelines. While the COVID-19 pandemic has impacted some areas of our business, we believe our mitigation efforts and financial strength will enable us to continue to manage through the pandemic and execute on our strategic initiatives. Because the situation is extremely fluid, we are continuing to evaluate the impact COVID-19 could have on our business, including the impact on our commercial products and the medicines in our pipeline.</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; Transformational Medicines 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 SMA 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;">SPINRAZA continues to demonstrate substantial benefit in SMA patients of all ages, supporting its position as a global foundation of care for the treatment of SMA. Biogen, our worldwide commercial partner, reported that as of December 31, 2020, there were more than 11,000 patients on SPINRAZA therapy with approval in over 50 countries around the world.</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, resulting in severe and progressive muscular atrophy and weakness. Ultimately, if untreated, individuals with the most severe type of SMA, infantile-onset, or Type 1, SMA, can become paralyzed and have difficulty performing the basic functions of life, like breathing and swallowing. Due to a loss of, or defect in, the </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, people with SMA do not produce enough SMN protein, which is critical for the maintenance of motor neurons. The severity of SMA correlates with the amount of SMN protein a patient can produce on his/her own. Patients with Type 1 SMA produce very little SMN protein and do not achieve the ability to sit without support or live beyond two years without respiratory support. Patients with later-onset, or Type 2 or Type 3 SMA, suffer from less severe, but still life-altering, forms of SMA. These patients produce greater amounts of SMN protein, but also experience progressive degeneration due to the disease.</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;">The approval of SPINRAZA was based on safety and efficacy 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 ongoing open label extension, or OLE, study for patients with SMA who participated in prior SPINRAZA studies.</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 is conducting DEVOTE, a Phase 2/3 study evaluating the safety and potential to achieve increased efficacy with a higher dose of SPINRAZA compared to the currently approved dose. The DEVOTE study is enrolling SMA patients of all ages, including adults. We and Biogen believe that SPINRAZA&#8217;s favorable long-term safety and tolerability profile observed in over 11,000 SMA patients of all ages, with some patients treated for up to 7 years, supports evaluation of higher SPINRAZA dosing.</div>
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<div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In January 2021, Biogen initiated the global Phase 4 RESPOND study evaluating the benefit of SPINRAZA in infants and children with a suboptimal clinical response to the gene therapy, </span>onasemnogene abeparvovec<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. RESPOND is a two-year, open-label study that Biogen is conducting at approximately 20 sites worldwide and is expecting to enroll approximately 60 children with SMA. The primary endpoint is the total score on the Hammersmith Infant Neurological Examination.</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;">For over six years, Biogen has been conducting the Phase 2 open-label NURTURE study, the first study investigating a treatment targeting the underlying cause of SMA in infants with the genetic diagnosis of SMA (most likely to develop SMA Type 1 or 2) before onset of symptoms. </span>Biogen published an interim analysis of the NURTURE data demonstrating SPINRAZA-treated infants achieved motor milestones in timelines more consistent with normal development than what is observed in the natural history of patients with Type 1 SMA. At the time of the interim analysis, all patients were alive and did not require respiratory intervention. All of the patients in the study were able to sit without support and 96 percent of the patients were able to walk either with assistance or independently. No new safety concerns were identified.</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 2018, SPINRAZA was recognized with the International Prix Galien Best Biotechnology Product award. The prestigious honor marks the seventh Prix Galien award for SPINRAZA, following country recognitions in the U.S., Germany, Italy, Belgium-Luxembourg, the Netherlands and the U.K. The International Prix Galien award is given every two years by Prix Galien International Committee members in recognition of excellence in scientific innovation to improve human health.</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;">TEGSEDI &#8211; </span>TEGSEDI (inotersen) injection is an RNA-targeted medicine indicated for the treatment of polyneuropathy of hereditary transthyretin-mediated amyloidosis in adults. TEGSEDI is commercially available in 15 countries, including the U.S., many European countries, Canada and 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;">TTR amyloidosis is a systemic, progressive and fatal disease caused by the formation and aggregation of TTR amyloid deposits in various tissues and organs, including peripheral nerves, heart, intestinal track, and central nervous system. There are an estimated 250,000 people worldwide with TTR amyloidosis.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">TTR amyloidosis that is the result of inherited mutations in the <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">TTR </span>gene is referred to as hATTR. There are an estimated 50,000 people worldwide with hATTR. There are two primary manifestations of hATTR: polyneuropathy and cardiomyopathy. Many people with hATTR often experience both manifestations, but often one manifestation or the other is diagnosed first and is more pronounced.</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 people with hATTR, both the mutant and wild type, or wt, TTR protein builds up as fibrils in tissues, such as peripheral nerves, heart, gastrointestinal system, eyes, kidneys, central nervous system, thyroid and bone marrow. The presence of TTR protein fibrils interferes with the normal function of these tissues. As the TTR protein fibrils enlarge, more tissue damage occurs and the disease worsens, resulting in poor quality of life and eventually death. We designed TEGSEDI to reduce the production of the TTR protein, the underlying cause of hATTR.</div>
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<div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">People without mutations in the <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">TTR</span> gene can also develop ATTR, often referred to as wild-type, or wt-ATTR. This non-hereditary form of the disease results from normal, non-mutant, TTR protein forming fibrils, primarily in the heart. People with hATTR cardiomyopathy and wt-ATTR experience ongoing debilitating heart damage resulting in progressive heart failure, which results in death within three to five years from disease onset. It is estimated that more than 200,000 people worldwide have wt-ATTR.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">TEGSEDI was recognized with the Prix Galien USA award for the Best Biotechnology Product in 2020. TEGSEDI is the second of our products to receive this prestigious honor.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The approvals of TEGSEDI were based on results from the Phase 3 NEURO-TTR study in patients with hATTR amyloidosis with stage 1 and stage 2 polyneuropathy. Results from that study demonstrated that patients treated with TEGSEDI experienced significant benefit compared to patients treated with placebo across both co-primary endpoints: the Norfolk Quality of Life Questionnaire-Diabetic Neuropathy, or Norfolk QoL-DN, and modified Neuropathy Impairment Score +7, or mNIS+7, a measure of neuropathic disease progression.<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> In July 2018, the final results from the NEURO-TTR pivotal study were published in </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">The New England Journal of Medicine.</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;">We also conducted an OLE study in patients with hATTR treated with TEGSEDI. This study was intended to evaluate the long-term efficacy and safety profile of TEGSEDI. </span>We reported interim data from the study that demonstrated continued efficacy in patients after two years and there were no new safety signals identified. Results also showed that patients who started treatment earlier achieved greater long-term disease stabilization compared to those who switched from placebo to TEGSEDI in the OLE study. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">The data from this study were published in </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">The European Journal of Neurology</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> in May 2020.</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;">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 pancreatitis, in whom response to diet and triglyceride lowering therapy has been inadequate.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">WAYLIVRA is commercially available in six European countries. We plan to launch WAYLIVRA in Brazil through our exclusive license agreement with PTC, assuming approval.</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 characterized by extremely elevated triglyceride levels that is estimated to affect 3,000 to 5,000 people worldwide. 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>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">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. People who have low levels of apoC-III or reduced apoC-III function have lower levels of triglycerides and a lower incidence of cardiovascular disease, or CVD. By inhibiting the production of apoC-III, WAYLIVRA is able to reduce triglyceride levels in people with high levels of triglycerides.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The conditional marketing authorization for WAYLIVRA <span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">is based on results from the Phase 3 APPROACH study, the ongoing APPROACH OLE study and supported by results from the Phase 3 COMPASS study.</span> The pivotal APPROACH study was a one-year, randomized, placebo-controlled study in 66 patients with FCS (average baseline triglycerides of 2,209 mg/dL, or 25.0 mmol/L). The study achieved its primary endpoint of reduction in triglycerides at three months, with a 77 percent mean reduction in triglycerides, which translated into a 1,712 mg/dL (19.3 mmol/L) mean absolute triglyceride reduction in WAYLIVRA-treated patients. We observed 50 percent of treated patients achieved triglyceride levels below 500 mg/dL, a commonly accepted threshold for pancreatitis risk. In addition, treatment with WAYLIVRA was associated with a statistically significant reduced rate of pancreatitis attacks in the group of patients who had the highest incidence of pre-study pancreatitis and reduced abdominal pain in patients reporting pain before treatment in the study. In August 2019, the final results from the APPROACH <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">pivotal study were published in </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">The New England Journal of 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;">An OLE study is ongoing for patients with FCS who have completed or meet the study criteria for the APPROACH and COMPASS studies. Additionally, we have expanded access programs, or EAPs, for WAYLIVRA.</div>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Drug Discovery and Development</div>
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<div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Introduction to Drug Discovery</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Proteins are essential working molecules in a cell. Almost all human diseases result from inappropriate protein production, improper protein activity or loss of a protein. Antisense medicines can modify the production of proteins by targeting RNAs. In this way, antisense medicines can inhibit the production of a disease-causing protein, modify the protein produced or increase the production of a protein that, when absent, causes diseases. Antisense medicines can also treat diseases by targeting and reducing RNAs that may be causing diseases (so called &#8220;toxic RNAs&#8221;). RNAs are naturally occurring molecules in the body that primarily act as messengers that carry the information the cell needs to produce proteins from the deoxyribonucleic acid, or DNA, to the protein making complex in the cell. When antisense medicines bind to the specific RNAs of a particular gene, they will ultimately alter the production of the protein encoded in the target gene or, in the case of disease-causing RNAs, degrade the toxic RNAs.</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;">Our Development Projects</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We are a leader in the discovery and development of antisense oligonucleotide medicines, or antisense medicines. By efficiently screening many targets in parallel to select the best candidates and applying our rational approach to selecting disease targets, we have built a robust portfolio of medicines designed to treat many serious diseases, such as cardiometabolic diseases, neurological diseases and others.</span>&#xA0;<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We are developing antisense medicines for systemic and local delivery (e.g., subcutaneous, intrathecal, intraocular, oral and aerosol).</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 plan to continue to add new investigational medicines to our pipeline creating opportunities to continue to generate substantial revenue. We also continue to improve our scientific understanding of our medicines, including how our medicines impact the biological processes of the diseases we target.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">With our expertise in discovering and characterizing novel antisense medicines, our scientists can optimize the properties of our antisense medicines against each particular target. Our scientists have made significant advances in chemical modifications we use in our antisense medicines, such as with our Generation 2+ antisense medicines, which have increased potency and an improved side effect profile over our earlier generation medicines. Our scientists have further improved upon our second-generation chemistry with our Generation 2.5 chemistry, an advancement that further increases the potency of our medicines, which broadens the organs and tissues in which our medicines can work. We currently have 17 Generation 2.5 medicines in development, and we anticipate that more of our future medicines will incorporate our Generation 2.5 chemistry.</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 improving the chemical foundation of our medicines, we have also created LIgand-Conjugated Antisense, or LICA, technology, which we design to enhance the effective uptake and activity of our medicines in particular tissues. With our LICA technology we attach specific chemical structures or molecules to our antisense medicines. With our first LICA conjugate, a complex sugar-like molecule called N-acetylgalactosamine, or GalNac, we have shown an increase in medicinal potency of 20-30-fold for liver targets, compared to non-conjugated antisense medicines. We currently have 15 LICA medicines in development, including three LICA medicines currently in Phase 3 studies, pelacarsen, for CVD, IONIS-TTR-L<sub>Rx</sub>, for all forms of ATTR and IONIS-APOCIII-L<sub>Rx</sub> for FCS. We also have four investigational medicines that combine our Generation 2.5 chemistry and LICA technology.</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 utilized our chemistry advancements, such as Generation 2.5 and LICA, to expand the therapeutic and commercial opportunities of our pipeline. These advancements, along with the manufacturing and analytical processes that are the same across our medicines, shorten our timeline from initial concept to the first human dose, when compared to early development timelines for other drug modalities like small molecule and antibody medicines.</div>
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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 8pt;">1. CVDRR: Cardiovascular disease risk reduction. 2. TG: Triglyceride. 3. sHTG: Severe hypertriglyceridemia.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The above table lists the medicines in our clinical pipeline. We categorize patient studies to establish a medicine&#8217;s safety profile as Phase 1/2 and those studies in healthy volunteers as Phase 1. The table includes the disease indication, a partner (if the medicine is partnered), and the development status of each medicine. We have included descriptions for each of our medicines in Phase 2 and Phase 3 development below.</div>
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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 focused on pioneering new markets and changing standards of care creating a deep and broad pipeline of over 30 potentially first-in-class and/or best-in-class medicines in clinical trials. We believe we have the potential to deliver significant value to patients affected by the devastating diseases each medicine addresses, many of which have limited or no treatment options.</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 Medicines</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 February 2020, we have five medicines in six Phase 3 studies: tofersen, tominersen, IONIS-TTR-L<sub>Rx</sub>, IONIS-APOCIII-L<sub>Rx</sub>, and 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;">Tofersen (</span>IONIS-SOD1<sub>Rx </sub>or BIIB067<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">) &#8211; </span>Tofersen is an investigational antisense medicine we designed to inhibit the production of superoxide dismutase 1, or SOD1, which is a well understood genetic cause of familial amyotrophic lateral sclerosis, or ALS. SOD1-<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">ALS is a rare, fatal, neurodegenerative disorder caused by a mutation in the </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">SOD1</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> gene leading to a progressive loss of motor neurons. As a result, people with SOD1-ALS experience increasing muscle weakness, loss of movement, difficulty breathing and swallowing and eventually succumb to the disease. Current treatment options for people with SOD1-ALS are extremely limited, with no medicines that significantly slow disease progression.</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;">Our partner, Biogen, conducted a Phase 1/2 study that demonstrated proof of biology and proof of concept. At the highest dose tested, treatment with tofersen over a three month period resulted in a statistically significant lowering of SOD1 protein levels in the CSF and positive numerical trends across three efficacy endpoints: slowing of clinical decline as measured by the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised, or ALSFRS-R, slowing of decline in respiratory function as measured by vital capacity and slowing of decline in muscle strength as measured by a handheld device, all compared to placebo. The efficacy, safety and tolerability profile in this study supported the continued development of tofersen in ALS.</div>
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<div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In December 2020, Biogen completed enrollment in the VALOR Phase 3 clinical study of tofersen. In the VALOR study Biogen is assessing the efficacy and safety of tofersen versus placebo in approximately 100 patients with SOD1-ALS. The primary endpoint of this study is an analysis based on the ALSFRS-R, which is a validated rating instrument that monitors the progression of disability in patients with ALS.</div>
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<div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In December 2018, Biogen exercised its option to license tofersen based on the positive interim analysis from the Phase 1/2 study. 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;">Tominersen (</span>IONIS-HTT<sub>Rx </sub>or RG6042<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">) &#8211; </span>Tominersen is an investigational antisense medicine we designed to target the underlying cause of Huntington&#8217;s disease, or HD, by reducing the production of the toxic mutant huntingtin protein, or mHTT. HD is a rare, inherited, genetic brain disorder that results in the progressive deterioration of mental abilities and physical control. In the U.S. and major European markets there are approximately 80,000 individuals with symptomatic HD and more than five-fold this number with presymptomatic HD. HD is one of several genetic diseases in which the body mistakenly repeats certain DNA sequences, often referred to as triplet repeat disorders. The resulting mHTT protein is toxic and gradually damages neurons in the brain. Symptoms of HD usually appear between the ages of 30 to 50 years and continually worsen over a 10 to 25-year period. Ultimately, the weakened individual succumbs to pneumonia, heart failure or other complications. Presently, there are no disease-modifying treatments available for HD patients, with current medicines only managing some disease symptoms.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We completed a randomized, placebo-controlled, dose escalation, Phase 1/2 clinical study of tominersen in patients with early stage HD. In this study, we observed dose-dependent reductions of mHTT among patients treated with tominersen. Tominersen also demonstrated a favorable safety and tolerability profile in this Phase 1/2 clinical study. In March 2018, we reported data from the study that demonstrated substantial reductions in the mHTT as observed in the cerebral spinal fluid, or CSF. The reductions in mHTT were in the target range that produced disease reversal in preclinical models of HD. Tominersen was the first medicine to demonstrate disease-modifying potential by lowering the root cause of HD, the mHTT protein. There were no serious adverse events reported and no participants discontinued from the study. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">The data from this study were published in </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">The New England Journal of Medicine</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> in May 2019.</span></div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Following the results from the Phase 1/2 study, Roche initiated the Phase 3 GENERATION HD1 study of tominersen and completed enrollment in April 2020. GENERATION HD1 is a randomized, multicenter, blinded, placebo-controlled study in approximately 800 patients with HD. The GENERATION HD1 study is evaluating the efficacy and safety of bi-monthly and tri-annual dosing regimens of tominersen for 25 months of dosing. The global primary endpoint is the change from baseline in the composite Unified Huntington Disease Rating Scale, or cUHDRS, and the U.S. primary endpoint is the change from baseline in the Total Functional Capacity, or TFC.</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 the Phase 3 study, all participants who took part in the Phase 1/2 study continued to receive tominersen as part of an OLE study to assess the safety and tolerability of tominersen. In parallel with the OLE, Roche initiated a natural history study in a similar patient population to the OLE. The natural history study is planned as a 15-month study aimed at further understanding the role of mHTT in disease progression and includes approximately 100 participants. There is no drug treatment in the natural history study, as the goal is to understand the natural progression of HD.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The European Medicines Agency, or EMA, granted PRIority MEdicines scheme, or PRIME, designation to tominersen. EMA PRIME status is granted to medicines that may offer a major therapeutic advantage over existing treatments, or benefit patients without treatment options. The FDA and EMA granted Orphan Medicine Designation for tominersen to treat people with HD.</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 entered into a collaboration with Roche to develop and commercialize antisense medicines to treat HD in April 2013. 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: 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-TTR-L</span><sub style="font-weight: bold;">Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">&#xA0;</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">&#8211; </span>IONIS-TTR-L<sub>Rx</sub>&#xA0;<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 transthyretin, the same protein inhibited by TEGSEDI (inotersen). There are two types of ATTR amyloidosis: hATTR amyloidosis and wt-ATTR amyloidosis. We are developing IONIS-TTR-L<sub>Rx</sub> as a monthly self-administered subcutaneous injection for the treatment of people with all forms of TTR amyloidosis. See the TEGSEDI summary under &#8220;Our Marketed Medicines&#8221; section for more information about hATTR amyloidosis and wt-ATTR amyloidosis.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In September 2019, we reported results from the Phase 1 study with IONIS-TTR-L<sub>Rx</sub> in healthy volunteers at the Heart Failure Society of America Annual Meeting. In this study, subjects treated with IONIS-TTR-L<sub>Rx</sub> achieved dose-dependent reductions of TTR protein of up to 94 percent and IONIS-TTR-L<sub>Rx</sub> demonstrated a favorable safety and tolerability profile, consistent with our other liver LICA medicines.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The first of two indications we are pursuing is for the treatment of patients with polyneuropathy caused by hATTR amyloidosis. We initiated the global NEURO-TTRansform Phase 3 study for IONIS-TTR-L<sub>Rx</sub> in November 2019. NEURO-TTRansform is <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">a multi-center, randomized, open-label study designed to evaluate the efficacy and safety of IONIS-TTR-L</span><sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> in up to 140 patients with polyneuropathy due to hATTR amyloidosis. The current study will be compared to the historical placebo arm from the TEGSEDI (inotersen) NEURO-TTR Phase 3 study that we completed in 2017. The NEURO-TTRansform study includes multiple primary endpoints, including the percent change from baseline in serum TTR concentration, modified Neuropathy Impairment Score +7 (mNIS+7), and in the Norfolk Quality of Life Questionnaire-Diabetic Neuropathy (Norfolk QoL-DN).</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 second indication we are pursuing is for the treatment of patients with cardiomyopathy caused by hereditary or wild-type TTR amyloidosis. In January 2020, we initiated the global CARDIO-TTRansform Phase 3 cardiovascular outcome study. CARDIO-TTRansform i<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">s </span>a randomized, blinded, placebo-controlled study in up to 750 patients with cardiomyopathy caused by hereditary or wt-TTR amyloidosis. The CARDIO-TTRansform study includes<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> co-</span>primary outcome measures of cardiovascular death and frequency of cardiovascular clinical events.</div>
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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-APOCIII-L</span><sub style="font-weight: bold;">Rx </sub><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">&#8211; </span>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 CVD. ApoC-III is also the target of WAYLIVRA (volanesorsen), the only medicine approved for the treatment of people with FCS. See the WAYLIVRA summary under &#8220;Our Marketed Medicines&#8221; section for more information about FCS.</div>
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<div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We initiated a Phase 3 study in December 2020 in patients with FCS based on the Phase 2 data described below. We believe that the enhancements offered by our LICA technology can provide greater reductions in triglycerides, significantly lower doses and less frequent administration, compared to WAYLIVRA.</div>
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<div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In January 2020, we reported positive results from a Phase 2 clinical study in patients</span> with hypertriglyceridemia and at high risk of or with established CVD. Patients were treated with multiple doses of IONIS-APOCIII-L<sub>Rx</sub> administered weekly, bi-weekly, or monthly. IONIS-APOCIII-L<sub>Rx</sub> achieved statistically significant, dose-dependent reductions in fasting triglycerides compared to placebo at all dose levels. Additionally, at the highest monthly dose, 91 percent of patients achieved serum triglycerides of &#8804; 150 mg/dL, the recognized threshold for cardiovascular risk, compared to less than 5 percent of patients in the placebo group. IONIS-APOCIII-L<sub>Rx</sub> also achieved statistical significance in numerous key secondary endpoints, including significant reductions in apoC-III, very low-density lipoprotein cholesterol, or VLDL-C, and remnant cholesterol, and a statistically significant increase in high-density lipoprotein cholesterol, or HDL-C. IONIS-APOCIII-L<sub>Rx</sub> demonstrated 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;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Pelacarsen </span>(IONIS-APO(a)-L<sub>Rx</sub> or 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</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">&#xA0;</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 lipoprotein(a), or 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. It is estimated that there are more than eight million people living with CVD and elevated levels of Lp(a). Inhibiting the production of Apo(a) in the liver reduces the level of Lp(a) in blood, potentially slowing down or reversing cardiovascular disease 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.</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 believe antisense technology is well suited to address hyperlipoproteinemia(a) because antisense technology specifically targets the RNA that codes for all forms of the Apo(a) molecule. Furthermore, we believe addressing elevated Lp(a) is the next important horizon in CVD risk reduction.</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;">&#xA0;</span>Novartis initiated the Phase 3 Lp(a)HORIZON study of pelacarsen, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">a global, randomized, blinded, placebo-controlled outcomes study in approximately 7,500 patients with </span>elevated Lp(a) levels and a prior cardiovascular event, based on the Phase 2 data described below. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Patients will be 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></div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We reported results of the Phase 2 study with pelacarsen in patients with hyperlipoproteinemia(a) at the American Heart Association, or AHA, annual meeting in November 2018. In this clinical study, we observed statistically significant and dose dependent reductions from baseline in Lp(a) levels. Approximately 98 percent of patients who received the highest dose in the study demonstrated a reduction in Lp(a) levels to below 50 mg/dL. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">This study of pelacarsen was </span>the longest and largest clinical study in patients with established CVD and elevated levels of Lp(a). At the time, this study was also the longest and largest clinical study of any of our LICA medicines. Pelacarsen demonstrated a favorable safety and tolerability profile in the study. Compliance in the treatment arm of the study was almost 90 percent, which was higher than what we observed in the placebo group.</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 initiated a collaboration with Novartis in January 2017 to advance pelacarsen.<span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;">&#xA0;</span>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; font-style: italic; font-weight: bold;">Neurological Disease 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 are discovering and developing antisense medicines to treat people with neurological diseases. Our neurological medicines address a broad range of diseases in major regions of the brain and all central nervous system, or CNS, cell types. Our antisense medicines aim to address both large and rare patient populations. We are currently investigating potential disease-modifying treatments for common neurological diseases including, Alzheimer&#8217;s disease and Parkinson&#8217;s disease. We also have multiple investigational medicines in clinical trials for rare neurological diseases, including ALS and hATTR polyneuropathy. According to the National Institute of Neurological Disorders and Stroke, or NINDS, at the National Institutes of Health, or NIH, a third of the 7,000 known rare diseases are neurological disorders or thought to include a neurological component.</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</span>&#8217;<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"> Neurological Disease Clinical Pipeline</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; font-weight: bold;"><span style="text-decoration: underline;">Wholly Owned Medicines</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-TTR-L</span><sub style="font-weight: bold;">Rx</sub> &#8211; See the medicine description under &#8220;Our Phase 3 Medicines&#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; font-weight: bold;"><span style="text-decoration: underline;">Partnered Medicines</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;">Tofersen</span> &#8211; See the medicine description under &#8220;Our Phase 3 Medicines&#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;">Tominersen</span> &#8211; See the medicine description under &#8220;Our Phase 3 Medicines&#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;">IONIS-C9</span><sub style="font-weight: bold;">Rx</sub> (BIIB078) &#8211; IONIS-C9<sub>Rx</sub> is an investigational antisense medicine we designed to selectively inhibit the production of the mutated chromosome 9 open reading frame 72, or <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">C9ORF72</span>, gene. A mutation in this gene results in an inherited form of ALS, referred to as C9ORF72-ALS, or C9-ALS, the most prevalent genetic cause of ALS worldwide. This mutation can lead to rapid progressive loss of motor neurons and is a fatal disease characterized by muscle weakness, loss of movement, and difficulty breathing and swallowing.</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 and Biogen are collaborating to develop IONIS-C9<sub>Rx</sub> to treat patients with this genetic form of ALS. In August 2018, Biogen initiated a Phase 1/2 clinical study evaluating IONIS-C9<sub>Rx</sub> in adult patients with C9ORF72-ALS. The current study is a randomized, blinded, placebo-controlled study designed to assess the safety, tolerability, and pharmacokinetics of multiple ascending doses of IONIS-C9<sub>Rx</sub> administered intrathecally. IONIS-C9<sub>Rx</sub> is the second medicine from our Biogen collaboration targeting a genetic form of ALS. The first is tofersen, our medicine we designed to treat SOD1 related ALS, caused by a mutation in the <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">SOD1</span> gene.</div>
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<div style="text-align: left; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">IONIS-MAPT</span><sub style="font-weight: bold;">Rx</sub> (BIIB080) &#8211; IONIS-MAPT<sub>Rx</sub> is an investigational antisense medicine we designed to selectively inhibit production of the microtubule-associated protein tau, or tau, protein in the brain. We are collaborating with Biogen to develop IONIS-MAPT<sub>Rx</sub> to treat people with Alzheimer&#8217;s disease, or AD, and potentially other neurodegenerative disorders characterized by the deposition of abnormal tau protein in the brain, such as certain forms of frontotemporal degeneration, or FTD, and progressive supranuclear palsy, or PSP.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The tau protein is a contributor or cause of certain neurodegenerative diseases, known as tauopathies, characterized by the deposition of abnormal tau protein in neurons in the brain. AD and FTD are characterized predominantly by memory impairment and behavioral changes, resulting in a person&#8217;s inability to independently perform daily activities. PSP is characterized by problems with walking and control of movement, sleep disorder and loss of memory and ability to reason. AD generally occurs late in life and may progress to death in five to 20 years after the onset of the disease. FTD and PSP have a more rapid disease progression. In the U.S., there are approximately five million people living with AD, approximately 55,000 people living with FTD and approximately 20,000 people living with PSP.</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 and Biogen completed a blinded, randomized, placebo-controlled, dose-escalation Phase 1/2 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. In February 2021, Biogen reported data from this Phase 1/2 study that IONIS-MAPT<sub>Rx</sub> was generally well tolerated and demonstrated dose and time-dependent target reductions. Biogen plans to advance IONIS-MAPT<sub>Rx</sub> into a Phase 2 clinical trial in patients with Alzheimer&#8217;s disease.</div>
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<div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In December 2019, Biogen exercised its option to license IONIS-MAPT<sub>Rx</sub>. We are responsible for completing the Phase 1/2 in study patients with mild AD and a one-year long-term extension study. Biogen will have 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: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span>12</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;">ION859 </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.</div>
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<div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">PD is a progressive neurodegenerative disease characterized by loss of neurons in the motor system. Patient&#8217;s 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 is no disease modifying therapy.</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 and Biogen are collaborating to develop ION859 to treat patients with PD. In August 2019, Biogen initiated a Phase 1/2 clinical study evaluating ION859 in adult patients with PD. The current study is a randomized, blinded, placebo-controlled study designed to assess the safety, tolerability and pharmacokinetics of multiple ascending doses of ION859 administered intrathecally.</div>
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<div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">ION464</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 as well as the primary pathology in PD and MSA patients without alpha-synuclein 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;">We and Biogen are collaborating to develop ION464 to treat patients with PD and MSA. In July 2020, Biogen initiated a Phase 1/2 clinical study evaluating ION464 in patients with MSA. The current study is a randomized, blinded, placebo-controlled study designed to assess the safety and tolerability of multiple doses of ION464 administered intrathecally.</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 </span>(BIIB105) &#8211; ION541 is an investigational antisense medicine we designed to selectively inhibit the production of the ataxin-2, or ATXN2, protein. In approximately 90% of the ALS population, aggregates of the TDP-43 protein induce toxicity in motor neurons. ATXN2 has been shown to modulate TDP-43 toxicity and it is believed that reduction of ATXN2 will decrease the TDP-43 aggregates and reverse or prevent disease progression, providing therapeutic benefit to most ALS 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;">We and Biogen are collaborating to develop ION541 to treat patients with most forms of ALS, regardless of family history. In October 2020, Biogen initiated a Phase 1/2 clinical study evaluating ION541 in this broad ALS population. The current study is a randomized, blinded, placebo-controlled study designed to assess the safety, tolerability, and pharmacokinetics of multiple ascending doses of ION541 administered intrathecally. ION541 is the first medicine from our Biogen collaboration targeting all forms 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;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">IONIS-DNM2-2.5</span><sub style="font-weight: bold;">Rx</sub> (DYN101) &#8211; IONIS-DNM2-2.5<sub>Rx</sub> is an investigational antisense medicine we designed to inhibit the production of Dynamin 2, or DNM2, protein for the treatment of centronuclear myopathy, or CNM. CNM is a group of rare, potentially fatal disorders of the skeletal muscle cells. It is characterized by muscle weakness, decreased muscle tone and muscle atrophy, ranging from severe to mild, and potentially life-threatening.</div>
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<div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">DNM2 reduction demonstrated improved muscle mass and muscle force, and extended lifespan in animal models of the most severe form of CNM.</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 and Dynacure are collaborating to develop IONIS-DNM2-2.5<sub>Rx</sub> to treat patients with CNM. In November 2019, Dynacure initiated a Phase 1/2 clinical study evaluating IONIS-DNM2-2.5<sub>Rx</sub> in patients with CNM. The current study is an open-label study designed to assess the safety and tolerability of multiple doses of IONIS-DNM2-2.5<sub>Rx</sub> administered intravenously.</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;">Cardiometabolic Disease 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;">Developing medicines targeting CVD and metabolic disorders are important areas of focus for us. According to the World Health Organization, or WHO, CVD remains the number one cause of death globally. An estimated 17.9 million people died from CVD in 2016, representing approximately 30 percent of all deaths globally. Our cardiovascular medicines target the major risk factors of cardiovascular disease, including cholesterol, triglycerides and hypertension. Metabolic disorders, such as nonalcoholic steatohepatitis, or NASH, are chronic diseases that affect tens of millions of people. There is a significant need for new therapies for these people. According to the American Liver Foundation, nonalcoholic fatty liver disease, or NAFLD, is the most common chronic liver condition in the U.S. It is estimated that about 25 percent of adults in the U.S. have NAFLD. Of those with NAFLD, about 20 percent have NASH or about 5% of adults in the U.S.</div>
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<div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">IONIS</span>&#8217;<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"> Cardiometabolic Disease Clinical Pipeline</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; font-weight: bold;"><span style="text-decoration: underline;">Wholly Owned Medicines</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-TTR-L</span><sub style="font-weight: bold;">Rx</sub> &#8211; See the medicine description under &#8220;Our Phase 3 Medicines&#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;">IONIS-APOCIII-L</span><sub style="font-weight: bold;">Rx</sub> &#8211; See the medicine description under &#8220;Our Phase 3 Medicines&#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;">IONIS-AGT-L</span><sub style="font-weight: bold;">Rx</sub>&#xA0;<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">&#8211;</span> IONIS-AGT-L<sub>Rx</sub> is an investigational LICA medicine we designed to inhibit the production of angiotensinogen to decrease blood pressure in people with treatment resistant hypertension, or TRH. Despite the availability of antihypertensive agents, TRH is still a major contributor to cardiovascular and renal 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;">Approximately 140 million adults globally and approximately 10 million adults in the U.S. have resistant hypertension, defined as failure to achieve a blood pressure goal of 140/90 (systolic/diastolic) despite the use of three or more antihypertensive medications. People with TRH have been found to have a three-fold higher chance of having fatal and non-fatal cardiovascular events relative to those with controlled hypertension.</div>
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<div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We evaluated IONIS-AGT-L<sub>Rx</sub> in two Phase 2 studies. The first study was in people with mild hypertension and the second was in people with TRH who were currently on two or three antihypertensive medications, including angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs). Each study was randomized, blinded, placebo-controlled and designed to evaluate the safety and tolerability of IONIS-AGT-L<sub>Rx</sub>.</div>
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<div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In January 2021, we initiated the Phase 2b clinical study of IONIS-AGT-L<sub>Rx</sub>, a randomized, blinded, placebo-controlled study in approximately 150 patients with TRH or uncontrolled hypertension who are currently on three or more antihypertensive medications, including ACE inhibitors or ARBs. The study is designed to evaluate multiple weekly doses administered subcutaneously. The primary endpoint is the change in systolic blood pressure (SBP) from baseline. The study will also assess numerous secondary endpoints, and safety and tolerability of 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; font-weight: bold;">IONIS-GHR-L</span><sub style="font-weight: bold;">Rx</sub> &#8211; IONIS-GHR-L<sub>Rx</sub> is an investigational LICA medicine we designed to inhibit the production of the growth hormone receptor, or GHr, to decrease the circulating level of insulin-like growth factor-1, or IGF-1. IGF-1 is a hormone primarily produced in the liver that plays an important role in childhood growth. Several different diseases result from abnormally low or high levels of IGF-1, or an inappropriate response to this hormone. Elevated levels of IGF-1 results in acromegaly, a chronic, slowly progressing and potentially fatal disease. Because IGF-1 mediates the majority of the growth-promoting action of GH, reducing GHr production could in turn decrease levels of IGF-1 and provide a potential treatment for patients with acromegaly.</div>
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<div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">High levels of circulating GH and IGF-1 lead to multiple diseases characterized by organ overgrowth and physical disfigurement, such as enlarged hands, feet, and facial features. Patients with acromegaly also experience multiple chronic conditions, such as type 2 diabetes, hypertension, and respiratory complications, as well as premature death. Current treatments to block IGF-1 are often unsuccessful. Drug treatments to normalize IGF-1 levels are also available but are associated with potentially serious side effects.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We completed a Phase 1, blinded, placebo-controlled, dose-escalation study of IONIS-GHR-L<sub>Rx</sub> in healthy volunteers. In this study, IONIS-GHR-L<sub>Rx</sub> demonstrated a favorable safety and tolerability profile.</div>
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<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span>14</span></div>
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<div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In November 2018, we initiated the Phase 2 proof of concept clinical study of IONIS-GHR-L<sub>Rx</sub> in patients with acromegaly. The study is a randomized, blinded, placebo-controlled, multi-center study in acromegaly patients uncontrolled on select long-acting somatostatin receptor ligands.</div>
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<div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In January 2021, we initiated a Phase 2 open label study evaluating </span>IONIS-GHR-L<sub>Rx</sub> as a monotherapy <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">in patients with acromegaly. The open label study is designed to assess the clinical efficacy, safety and tolerability of </span>IONIS-GHR-L<sub>Rx</sub> of multiple doses <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">administered monthly subcutaneously.</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; font-weight: bold;"><span style="text-decoration: underline;">Partnered Medicines</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;">Pelacarsen</span> &#8211; See the medicine description under &#8220;Our Phase 3 Medicines&#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;">Vupanorsen </span><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;">&#8211; </span>Vupanorsen is an investigational LICA medicine we designed to inhibit the production of the angiopoietin-like 3, or ANGPTL3, protein. People with elevated levels of the ANGPTL3 protein have high LDL-C and triglyceride levels. Studies show people with elevated levels of ANGPTL3 protein have an increased risk of premature heart attacks, increased arterial wall thickness and multiple metabolic disorders such as diseases resulting from increased liver fat. In contrast, people with lower levels of ANGPTL3 have lower LDL-C and triglyceride levels, and thus lower risk of heart attacks, lower prevalence of fatty liver and lower incidence of metabolic disorders.</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 preclinical studies, treatment with an antisense medicine designed to inhibit the production of the ANGPTL3 protein in the liver resulted in lower liver fat accumulation and lower blood levels of LDL-C, triglycerides and very low-density lipoprotein cholesterol, or VLDL-C.</div>
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<div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Results from a Phase 1/2 study of vupanorsen in healthy volunteers with elevated triglycerides were published in <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">The</span>&#xA0;<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">New England Journal of Medicine</span>. In the study, we observed that the people with elevated triglycerides achieved dose-dependent, statistically significant mean reductions in ANGPTL3 of up to 83 percent. Treatment with vupanorsen was also associated with statistically significant mean reductions in triglycerides of up to 66 percent, in LDL-C of up to 35 percent and in total cholesterol of up to 36 percent. In this study, vupanorsen demonstrated a favorable safety and tolerability profile.</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 2020, Pfizer initiated the Phase 2b TRANSLATE-TIMI 70 clinical study of vupanorsen, a randomized, blinded, placebo-controlled study in approximately 260 patients with elevated non-HDL-C and triglycerides who are receiving a stable dose of a statin, based on the Phase 2 study described below. The study is designed to evaluate multiple doses and dose regimens versus placebo. The primary endpoint is percent change from baseline in non-HDL-C. The study will also assess the efficacy, safety, tolerability and pharmacokinetics of vupanorsen.</div>
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<div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In January 2020, we reported positive results from a Phase 2 clinical study in patients</span> with elevated levels of triglycerides, or hypertriglyceridemia, type 2 diabetes and NAFLD. Patients were treated with multiple doses of vupanorsen administered weekly and monthly. Vupanorsen achieved statistically significant, dose-dependent reductions in the study&#8217;s primary endpoint of fasting triglycerides compared to placebo at all dose levels. Vupanorsen also achieved statistical significance in multiple secondary endpoints, including dose-dependent reductions in ANGPTL3, apoC-III, very low-density lipoprotein (VLDL-C), non-HDL cholesterol and total cholesterol compared to placebo. Vupanorsen demonstrated a favorable safety and tolerability profile in the study.</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 October 2019, we exclusively licensed </span>vupanorsen <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">to Pfizer. As a result, Pfizer is </span>responsible for global development, regulatory and commercialization activities and costs beyond those associated with the above Phase 2 study. We have the option prior to regulatory filing for marketing approval, to participate in certain commercialization activities in the future with Pfizer in the U.S. and certain additional markets on pre-defined terms and based on meeting pre-defined criteria.</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-FXI-L</span><sub style="font-weight: bold;">Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"> &#8211; </span>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. High levels of Factor XI increase the risk of thrombosis. 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 IONIS-FXI-L<sub>Rx</sub> can be used broadly as an anti-thrombotic in many different therapeutic settings for which 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 2016, we completed a Phase 2 blinded, randomized, placebo-controlled study of the parent medicine, IONIS-FXI<sub>Rx</sub>, in people with end-stage renal disease, or ESRD, on hemodialysis. In this Phase 2 study, patients treated with IONIS-FXI<sub>Rx</sub> achieved statistically significant, dose-dependent reductions in Factor XI activity. In this study, IONIS-FXI<sub>Rx</sub> demonstrated a favorable safety and tolerability profile. There were no treatment-related major or clinically relevant non-major bleeding events.</div>
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<div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We conducted a Phase 1, blinded, randomized, placebo-controlled, dose-escalation study of IONIS-FXI-L<sub>Rx </sub>in healthy volunteers. In this study, IONIS-FXI-L<sub>Rx</sub> produced significant reductions in FXI activity and FXI antigen, without evidence of increased bleeding. Additionally, IONIS-FXI-L<sub>Rx</sub> demonstrated a favorable safety and tolerability profile in this study. We and Bayer are planning to report the data from this Phase 1 study this year.</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 2017, we licensed IONIS-FXI-L<sub>Rx</sub> to Bayer. As a result, Bayer is responsible for global development, regulatory and commercialization activities and costs.</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 2020, Bayer initiated the Phase 2b RE-THINc clinical study of IONIS-FXI-L<sub>Rx</sub>, a randomized, blinded, placebo-controlled study in approximately 290 patients with ESRD on hemodialysis. The study is designed to evaluate multiple monthly doses administered subcutaneously. The primary endpoint is incidence of major bleeding and clinically relevant non-major bleeding. The study will also assess numerous secondary endpoints, and safety and tolerability of IONIS-FXI-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; font-weight: bold;">ION449</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> &#8211; ION449 (IONIS-AZ4-2.5-L</span><sub>-Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">) </span>is an investigational LICA medicine we designed to reduce the production of proprotein convertase subtilisin/kexin type 9, or PCSK9, in the liver. PCSK9 is integrally involved in the regulation of LDL-cholesterol. Genetic studies have shown that individuals with life-long reductions of LDL-C due to reduced function of PCSK9 have substantially reduced risk of CVD.</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, we reported positive results from a Phase 1 clinical study of ION449 in healthy volunteers. Participants were treated with single subcutaneous doses and ION449 demonstrated dose-dependent mean reductions in circulating plasma PCSK9 and LDL-C levels of greater than 90% and up to 70%, 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 November 2020, AstraZeneca initiated the Phase 2b randomized, blinded placebo-controlled clinical study that will enroll approximately 110 patients with LDL-C levels between 70 and 190mg/dl and receiving statin therapy. The study is designed to evaluate multiple monthly subcutaneous doses versus placebo. The study will also assess safety and tolerability, and multiple secondary endpoints.</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-GCGR</span><sub style="font-weight: bold;">Rx</sub> &#8211; IONIS-GCGR<sub>Rx</sub> is an investigational antisense medicine designed to inhibit the production of the glucagon receptor, or GCGR, to treat patients with type 2 diabetes. GCGR is a receptor for the hormone glucagon. Glucagon is a hormone that opposes the action of insulin and stimulates the liver to produce glucose, particularly in type 2 diabetes. In patients with advanced diabetes, uncontrolled glucagon action can lead to significant increase in blood glucose level. In addition, reducing GCGR produces more active glucagon-like peptide, or GLP-1, a hormone that preserves pancreatic function and enhances insulin secretion.</div>
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<div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Diabetes is a chronic disease in which the blood glucose levels are too high. Although glucose is an important source of energy for your body and is vital to your health, uncontrolled increases in glucose can lead to serious health problems, such as diabetes. Diabetes is separated into type 1 and type 2. In type 1 diabetes, the body does not make insulin. In type 2 diabetes, the more common type, the body does not respond properly to insulin and, therefore, blood glucose levels are not adequately controlled.</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 and Suzhou-Ribo are collaborating to develop IONIS-GCGR<sub>Rx</sub> to treat patients with type 2 diabetes. In October 2019, Suzhou-Ribo initiated a Phase 2 clinical study evaluating IONIS-GCGR<sub>Rx</sub> in patients with type 2 diabetes.</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 continue to advance medicines in clinical development that are outside of our core franchises, such as medicines targeting pulmonary diseases, cancer and infectious 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;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">IONIS</span>&#8217;<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"> Other Medicines in Clinical Pipeline</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; font-weight: bold;"><span style="text-decoration: underline;">Wholly Owned Medicines</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;">IONIS-ENAC-2.5</span><sub style="font-weight: bold;">Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"> &#8211; </span>IONIS-ENAC-2.5<sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">&#xA0;</span>is an investigational antisense medicine we designed to selectively reduce epithelial sodium channel, or ENaC, to treat people with cystic fibrosis, or CF, and chronic obstructive pulmonary disease, or COPD. CF is an autosomal recessive disorder caused by mutations in the gene that encodes the cystic fibrosis transmembrane conductance regulator, or CFTR. CFTR is a chloride channel expressed in epithelial cells, including those in the lung. Targeting ENaC may enable treatment of all forms of CF regardless of CFTR mutations, unlike existing therapeutics. CF is a multisystem disease that mostly affects the lungs, clogging airways due to mucus build-up and resulting in inflammation and infection. This disease is characterized by a progressive decline in lung function with acute periods of worsened symptoms, known as pulmonary exacerbations. Despite progress with other treatments, there remains a need for additional effective treatment options.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In preclinical studies in mouse models of CF, treatment with ENaC-targeting antisense medicines specifically suppressed ENaC expression, resulting in the reduction of markers of CF mucus pathology and improved lung function. Treatment not only prevented manifestations of the disease from occurring but also reversed existing manifestations of disease in the animal model.</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 2018, we initiated a Phase 1/2 blinded, placebo-controlled, dose-escalation study to evaluate the safety and efficacy of IONIS-ENAC-2.5<sub>Rx </sub>delivered directly to the lung via a nebulizer. The study consisted of three parts: a single ascending dose, or SAD, regimen and a multiple ascending dose, or MAD, regimen in healthy volunteers, followed by a MAD regimen in patients with CF.</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 October 2020, we reported positive results from the healthy volunteer portions of the Phase 1/2 study. IONIS-ENAC-2.5</span><sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> demonstrated a significant decrease in the expression of ENaC with a favorable safety and tolerability profile, representing proof-of-concept for pulmonary delivery of an antisense medicine directly to the lung. In November 2020, we</span> completed enrollment in the MAD portion in patients with CF.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">COPD is a progressive and chronic inflammatory lung disease that causes obstructed airflow in the lungs and is the third leading cause of death globally. It is estimated to affect approximately 16 million people in the U.S. Targeting ENaC is believed to increase airway surface hydration and improve lung clearance.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In a preclinical mouse model of woodsmoke, treatment with an ENaC-targeting antisense medicine through aerosol delivery resulted in broad distribution in the lung and improved lung function.</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 2020, we initiated a Phase 1/2 study in patients with COPD with chronic bronchitis. The current study is a blinded, placebo-controlled, single dose study to evaluate the safety and efficacy of IONIS-ENAC-2.5<sub>Rx</sub> delivered directly to the lung via a nebulizer.</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-PKK-L</span><sub style="font-weight: bold;">Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"> &#8211; </span>IONIS-PKK-L<sub>Rx</sub> is an investigational LICA medicine we designed to inhibit the production of prekallikrein, or PKK, to treat people with hereditary angioedema, or HAE. It is a rare genetic disease that is characterized by rapid and painful attacks of inflammation in the hands, feet, limbs, face, abdomen, larynx and trachea and can be fatal if swelling occurs in the larynx. PKK plays an important role in the activation of inflammatory mediators associated with acute attacks of HAE. By inhibiting the production of PKK, IONIS-PKK-L<sub>Rx</sub> could be an effective prophylactic approach to preventing or reducing the severity of HAE attacks.</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 August 2019, we initiated a Phase 2 study evaluating </span>IONIS-PKK-L<sub>Rx</sub>&#xA0;<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">in patients with HAE. The current study is a randomized, blinded, placebo-controlled study designed to assess the clinical efficacy, safety and tolerability of </span>IONIS-PKK-L<sub>Rx</sub>&#xA0;<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">administered subcutaneously.</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;">Results from the Phase 1 study in healthy volunteers and a compassionate-use study of IONIS-PKK<sub>Rx</sub> and IONIS-PKK-L<sub>Rx</sub> in patients living with severe bradykinin-mediated angioedema were published in September 2020 in <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">The</span>&#xA0;<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">New England Journal of Medicine</span>. In the study, we observed that the medicines reduced plasma prekallikrein activity levels and showed evidence of clinical efficacy in reducing the number of breakthrough attacks per month in patients over the course of the treatment, including complete resolution in a patient with Type 1 HAE, the most common form 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;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Danvatirsen &#8211; </span>Danvatirsen (formerly IONIS-STAT3-2.5<sub>Rx</sub>) is an investigational antisense medicine we designed to inhibit the production of signal transducer and activator of transcription 3, or STAT3, to treat people with cancer. STAT3 is a protein involved in the translation of key factors critical for tumor cell growth and survival. STAT3 is over-active in a variety of cancers, including brain, lung, breast, bone, liver and multiple myeloma. Overactivity in STAT3 prevents cancer cell death and promotes tumor cell growth.</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 2018, we announced data from a Phase 1/2 study of danvatirsen in combination with durvalumab in recurrent metastatic head and neck cancer. The combination treatment resulted in seven percent of patients achieving a complete tumor response and 23 percent achieving either a partial or complete tumor response. This response rate is estimated to be double that with durvalumab alone, based on previous studies in this difficult to treat patient population. Results from this study demonstrated a 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;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">IONIS-TMPRSS6-L</span><sub style="font-weight: bold;">Rx</sub> &#8211; IONIS-TMPRSS6-L<sub>Rx</sub> is an investigational LICA medicine we designed to inhibit the production of transmembrane protease, serine 6, or TMPRSS6, to treat anemia and iron toxicity in people with &#946;-thalassemia, a disease caused by mutations in the <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">beta globin</span> gene. TMPRSS6 is a protein produced in the liver that is important in the regulation of the body&#8217;s iron homeostasis through the control of the iron regulatory protein hepcidin. Inhibition of TMPRSS6 leads to increased production of hepcidin, which results in more effective red blood cell production in the bone marrow and reduced iron toxicity in multiple organs, including the liver as a result of improved control of iron availability.</div>
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<div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Patients with &#946;-thalassemia can experience severe anemia, marrow expansion, bone deformities, as well as iron toxicity. While the severity of anemia varies between patients, iron toxicity is a common complication leading to high rates of mortality as a result of iron accumulation in major organs, such as the heart and liver. The current standard of care is managing patients&#8217; symptoms with blood transfusions, and iron chelation medicines designed to remove extra iron from blood.</div>
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<div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#946;-thalassemia can be further subdivided into patients with transfusion-dependent thalassemia, or TDT, and non-transfusion dependent thalassemia, or NTDT, including &#946;-thalassemia intermedia. Although transfusions are not needed to support life in patients with NTDT, the associated complications of the disease are severe and often fatal.</div>
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<div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Results from preclinical and clinical studies suggest that reducing levels of TMPRSS6 may be an effective strategy to control iron availability, reduce liver iron toxicity and increase red blood cell production under conditions of &#946;-thalassemia. In a randomized, blinded, placebo-controlled, dose-escalation Phase 1 study in healthy volunteers, we demonstrated dose-dependent reductions of serum iron and serum transferrin saturation. Additionally, we observed an increase in serum hepcidin and predicted changes in hemoglobin. IONIS-TMPRSS6-L<sub>Rx</sub> demonstrated a favorable safety and tolerability profile. In December 2018, we presented positive Phase 1 data at the American Society of Hematology Annual Meeting.</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 August 2020, we initiated a Phase 2a open label study evaluating </span>IONIS-TMPRSS6-L<sub>Rx</sub>&#xA0;<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">in patients with </span>NTDT &#946;-thalassemia intermedia<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. The open label study is designed to assess the clinical efficacy, safety and tolerability of </span>IONIS-TMPRSS6-L<sub>Rx</sub>&#xA0;<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">administered monthly subcutaneously.</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; font-weight: bold;"><span style="text-decoration: underline;">Partnered Medicines</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;">IONIS-HBV</span><sub style="font-weight: bold;">Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"> &#8211; </span>IONIS-HBV<sub>Rx</sub> is an investigational antisense medicine we designed to inhibit the production of viral proteins associated with hepatitis B virus, or HBV. These include proteins associated with infection and replication, including the hepatitis B surface antigen, or HBsAg, which is present in both acute and chronic infections and is associated with a poor prognosis in people with chronic HBV infection.</div>
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<div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">HBV infection is a serious health problem that can lead to significant and potentially fatal health conditions, including cirrhosis, liver failure and liver cancer. Chronic HBV infection is one of the most common persistent viral infections in the world. 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;">GSK reported results of the Phase 2 study with IONIS-HBV<sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">&#xA0;</span>in patients with chronic hepatitis B virus infection at the American Association for the Study of Liver Diseases annual meeting in November 2019. In the Phase 2 study with IONIS-HBV<sub>Rx</sub>, the medicine demonstrated target engagement with dose dependent declines in HBsAg with up to 3-log reductions in HBsAg at one month, including two patients who achieved reductions in HBsAg and HBV DNA below levels of detection. Additionally, IONIS-HBV<sub>Rx</sub>&#xA0;<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">demonstrated a favorable safety and tolerability profile.</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 Phase 2 results described above. 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 August 2020, GSK launched a broad Phase 2 program and initiated the Phase 2b B-Clear clinical study of IONIS-HBV<sub>Rx</sub> in patients with chronic hepatitis B virus. The Phase 2b B-Clear study is a randomized, blinded, placebo-controlled study in approximately 440 patients with chronic hepatitis B virus infection. The primary endpoint is the percentage of patients achieving HBV surface antigen and HBV DNA less than the lower limit of quantitation. The study will also assess multiple secondary endpoints and the safety and tolerability of IONIS-HBV<sub>Rx</sub>.</div>
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<div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In the fourth quarter of 2020, GSK initiated two open label Phase 2 studies, B-Fine and B-Together, in patients with chronic hepatitis B virus. The B-Fine clinical study of IONIS-HBV<sub>Rx</sub> is designed to investigate the hepatitis B virus surface antigen and assess liver biopsy samples for phenotyping. The B-Together study is designed to investigate if treatment of IONIS-HBV<sub>Rx</sub> followed by pegylated interferon treatment can increase the rate of hepatitis B virus surface antigen loss in patients on stable nucleoside analogue therapy.</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-AR-2.5</span><sub style="font-weight: bold;">Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"> &#8211;</span> IONIS-AR-2.5<sub>Rx</sub> is an investigational antisense medicine we designed to treat people with prostate cancer by reducing the production of all known forms of androgen receptor, or AR, including variants of the <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">AR</span> gene. Prostate cancer is the second leading cause of cancer deaths in American men. Prostate cancer growth, proliferation and progression are all androgen-dependent and AR function is involved in disease progression at all stages of prostate cancer. For patients diagnosed with metastatic prostate cancer, current treatments largely involve opposing the action of androgens by blocking the androgen receptor or removing circulating androgens. Resistance to current therapies is frequent and can occur through a variety of mechanisms including the activation of AR signaling in tumor cells through the amplification, overexpression and mutation of the <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">AR </span>gene.</div>
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<div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">An open-label, dose-escalation, Phase 1/2 clinical study of IONIS-AR-2.5<sub>Rx</sub> was completed in people with advanced tumors for which the androgen receptor pathway is potentially a contributing factor. The study was primarily conducted in prostate cancer patients and it showed durable responses in a number of those patients. Results from this study demonstrated a 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 March 2017, we licensed IONIS-AR-2.5<sub>Rx</sub> to Suzhou-Ribo to develop and commercialize the medicine in China.</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;">&#xA0;</span>&#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;"> is an investigational LICA medicine we designed to inhibit the production of complement factor B, or FB. FB is produced predominantly in the liver and circulates at high levels throughout the vascular system where it plays a pivotal role in an innate immunogenic cascade. Genetic association studies have shown that overactivity of this cascade has been associated with the development of several complement-mediated diseases, including dry age-related macular degeneration, or AMD, and IgA nephropathy, or IgAN.</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. It is estimated that the disease will affect more than three million people in the U.S. by 2026. AMD is believed to be a systemic disease with local disease manifestation at the aging retinal macula. AMD gradually destroys vision in the center of the visual field due to progressive damage of the retina. Geographic atrophy, or GA, is an advanced form of AMD and accounts for approximately fifteen percent of all 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;">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 renal failure. Also known as Berger&#8217;s disease, IgAN is characterized by deposits of IgA in the kidneys, resulting in inflammation and tissue damage. The clinical presentation, disease progression and histologic findings are highly variable.</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 2017, we reported data from a randomized, placebo-controlled, dose-escalation Phase 1 study evaluating IONIS-FB-L<sub>Rx</sub> in 54 healthy volunteers. Subjects treated with a single dose of IONIS-FB-L<sub>Rx</sub> achieved dose-dependent reductions in plasma FB of up to 50 percent. Treatment with multiple doses of IONIS-FB-L<sub>Rx</sub> during a six-week period resulted in greater reductions in circulating FB levels. In this study, IONIS-FB-L<sub>Rx</sub> demonstrated 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;">We and Roche are collaborating to develop IONIS-FB-L<sub>Rx</sub> for the treatment of complement-mediated diseases. In June 2019, we initiated a Phase 2 study evaluating IONIS-FB-L<sub>Rx</sub> in patients with geographic atrophy secondary to age-related macular degeneration. The study is a randomized, masked, placebo-controlled study designed to assess the safety, tolerability and pharmacokinetics of multiple ascending doses of IONIS-FB-L<sub>Rx</sub> administered subcutaneously in adults with geographic atrophy.</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 2019, we initiated a Phase 2 study of IONIS-FB-L<sub>Rx</sub> in patients with IgA nephropathy. The current study is a single-arm, open-label study designed to assess the safety, tolerability and pharmacokinetics of IONIS-FB-L<sub>Rx</sub> administered subcutaneously in adults with primary IgA nephropathy.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">ION357 &#8211; </span>ION357 (IONIS-RHO-2.5<sub>Rx</sub>), is an investigational antisense medicine we designed to treat patients with a genetic form of autosomal dominant retinitis pigmentosa by inhibiting the production of the rhodopsin P23H mutant protein in the eye while allowing normal protein to be expressed.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Retinitis pigmentosa, or RP, is a group of rare inherited eye disorders causing photoreceptor degeneration that leads to progressive vision loss. Photoreceptors are cells in the eye&#8217;s retina responsible for converting light into signals that are sent to the brain. Photoreceptors provide us our color and night vision. Affected patients first experience defective dark adaptation during adolescence or young adulthood, followed by loss of peripheral visual field. Patients eventually have limited residual central vision, which ultimately leads to complete blindness around the age of 60.</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;">We and ProQR </span>are collaborating to develop <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">ION357 </span>to treat patients with RP. In November 2019, ProQR initiated a Phase 1/2 clinical study evaluating <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">ION357</span> in patients with RP. The current study is a randomized, masked, placebo-controlled study designed to assess the safety and tolerability of <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">ION357</span> in adult patients with RP.</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;">Phase 1 Medicines in Clinical 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;">The efficiency and broad applicability of our technology enables us to develop medicines for a broad range of diseases. In 2020, we initiated six Phase 1 or Phase 1/2 studies.</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</span>&#8217;<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"> Phase 1 and Preclinical Pipeline</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; font-weight: bold;">Antisense 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;">Our antisense technology is an innovative platform for discovering first-in-class and/or best-in-class medicines and represents an important advance in the way we treat disease. 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. The unique properties of antisense technology provide several advantages over traditional drug discovery technologies.</div>
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<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">These advantages include:</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;">Direct intervention in the disease process at the genetic level by targeting RNA: antisense technology represents a direct route from gene to drug. The explosion in genomic information and RNA biology has led to the discovery of many new disease-causing proteins and RNAs and has created new opportunities that are uniquely accessible by antisense technology.</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;">Precise specificity: we design antisense medicines to target a single RNA, which minimizes the possibility of binding to unintended targets, which can cause unwanted side effects.</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;">Good drug properties: antisense medicines distribute well throughout the body without the need for special formulations or vehicles. They also have a long half-life, in the range of weeks to months, which means patients and/or healthcare providers can dose our medicines weekly, monthly or even less frequently depending on the medicine and target tissue.</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;">Ability to combine with other medicines: because antisense medicines do not interact with the enzymes that metabolize or break down other medicines, physicians can use our medicines in combination with other medicines.</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;">Broad applications to multiple disease targets, multiple tissues and multiple mechanisms: there are virtually no &#8220;undruggable&#8221; targets with antisense technology.</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;">Efficient discovery and early development: because of the efficiency of our antisense technology, our drug discovery and early development costs and success rates compare favorably to small molecule or antibody drug discovery and development.</div></td>
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<div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We develop antisense medicines we believe will pioneer new markets and change standards of care across a wide range of diseases, including neurological and cardiometabolic 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;">Technology Overview</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 use our core technology platform to discover and develop medicines that affect targets in the body at the genetic level. Genes contain the information necessary to produce proteins. A gene is made up of nucleotides containing the nucleoside bases: adenine, thymine, guanine, and cytosine, commonly known as A, T, G and C, which are linked together to form a two-stranded structure that resembles a twisted ladder, known as DNA. The nucleotides on one side of the ladder bind weakly to complementary nucleotides on the other strand according to specific rules; for example, A pairs with T and G pairs with C, creating the ladder&#8217;s rungs (Figure 1). Scientists call this highly specific nucleotide pairing hybridization. The sequence or order of these nucleotides establishes the cell&#8217;s recipes for making proteins. Each protein&#8217;s instructions reside in a corresponding segment of DNA known as a gene.</div>
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<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Figure 1: Illustration of DNA.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The instructions for making a protein are transcribed from a gene, or DNA, into a different genetic molecule called messenger RNA. This process starts with the partial uncoiling of the two complementary strands of the DNA. One strand acts as a template and information stored in the DNA template strand is copied into a complementary RNA (Figure 2) by an enzyme called RNA polymerase, or RNAP. Messenger RNA, or mRNA, are mature, fully processed RNA that code for proteins.</div>
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<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Figure 2: Transcription of information contained in a gene, or DNA, to RNA.</div>
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<div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Ribosomes, the cell&#8217;s factories for manufacturing proteins, translate mRNA into proteins. The ribosome reads the encoded information, the mRNA&#8217;s nucleotide sequence, and in doing so, strings together amino acids to form a specific protein (Figure 3).</div>
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<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Figure 3: Translation of the protein-coding information contained in mRNA to protein.</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 primarily use our antisense technology to interrupt the cell&#8217;s protein production process by preventing the mRNA instructions from reaching the ribosome, thus inhibiting the production of the protein. We can also design antisense medicines to increase protein production for diseases caused by the lack of a particular protein or modify the processing (or splicing) of the mRNA, which can alter the composition of the protein. The mRNA sequence of nucleotides that carries the information for protein production is called the &#8216;sense&#8217; strand. Scientists call the complementary nucleotide chain that binds specifically to the sense strand the &#8220;antisense&#8221; strand. We use the information contained in mRNA to design chemical structures, that we call antisense oligonucleotides, or ASOs, or antisense medicines, which resemble DNA and RNA and are the complement of RNA. Our antisense medicines bind with high selectivity to the mRNA they were designed to target. Since each mRNA codes for a specific protein, we can design antisense medicines that selectively inhibit the disease-causing member of a protein family without interfering with other members of the protein family that might be necessary for normal cellular or bodily functions. This unique specificity means that antisense medicines may be less toxic than traditional medicines because we can design them to minimize the impact on unintended targets.</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 developed the majority of the medicines in our pipeline using our advanced screens to produce medicines with what we believe have the best possible safety and tolerability profiles. We continue to advance our antisense technology to create even more potent medicines that we can use in more tissues and against more targets. These advances allow us to expand the mechanisms through which we can use our medicines and provide us with greater opportunities to use our antisense medicines to treat a greater number of diseases and reach more patients. Today our medicines and those entering our pipeline utilize our key technology advances, including our next generation chemistry, Generation 2.5, and our LICA 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;">Generation 2.5 chemistry, used in several medicines in our pipeline, enables up to 10-fold greater potency compared to our medicines using our earlier chemistries. This increased potency enables broad distribution throughout the body and target engagement to multiple tissues including liver, kidney, lung, muscle, adipose, adrenal gland, peripheral nerves and tumor tissues. Our Generation 2.5 medicines constitute some of the new medicines we recently added to our pipeline.</div>
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<div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">LICA is a chemical technology we developed that involves attaching a molecule called a ligand that binds with receptors on the surfaces of cells in a highly specific manner. Because these receptors are often found only on certain cell types, LICA allows us to increase effective delivery of our antisense medicines with higher specificity to certain cell types that express these receptors relative to non-conjugated antisense medicines. As of December 2020, we have an integrated assessment of data from multiple LICA medicines and over 1,200 subjects who have been treated with our LICA medicines, which demonstrates that our LICA technology for liver targets can increase potency by 20-30-fold over our non-LICA antisense medicines.</div>
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<div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In addition to the increase in potency, the LICA platform has consistently demonstrated favorable safety and tolerability. Pelacarsen exemplifies these improvements. We designed this medicine to reduce the production of Apo(a) protein in the liver to offer a direct approach for reducing Lp(a). Pelacarsen was the first and only medicine to selectively and robustly reduce Lp(a) levels below threshold levels associated with CVD in nearly all patients and demonstrated a favorable safety and tolerability profile in the Phase 2 study. The study included more than 280 patients, with 98 percent of patients in the high dose group achieving levels below 50 mg/dL, the recognized risk threshold for CVD.</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 can also combine our LICA technology with our Generation 2.5 chemistry, further increasing potency. This increase in potency may enable oral delivery of our antisense medicines. In addition to the LICA technology for liver targets, we are also developing LICA conjugation technology that we can use to target other tissues, such as muscle, and initial results are promising.</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;">Antisense Targets and Mechanisms</div>
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<div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">There are more than a dozen different antisense mechanisms that we can utilize with our antisense technology. The majority of the medicines in our pipeline bind to mRNAs and inhibit the production of disease-causing proteins. However, our antisense technology is broadly applicable to many different antisense mechanisms, including modulation of RNA splicing, RNA interference, or RNAi, and enhancing protein translation to increase protein production.</div>
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<div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">When using antisense technology to inhibit the production of disease-causing proteins or reduce levels of harmful RNAs, our antisense medicines bind to the target RNA via highly specific nucleotide pairing, or hybridization, and recruit a cellular enzyme called ribonuclease H1, or RNase H1, to degrade the target RNA. The antisense medicine itself remains intact during this process, so it can remain active against additional target RNA molecules and repeatedly trigger their degradation (Figure 4). Examples of our antisense medicines that use the RNase H1 mechanism to reduce disease protein production include, TEGSEDI, WAYLIVRA, tominersen, pelacarsen, and others.</div>
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<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Figure 4: Antisense medicine using the RNase H mechanism of action.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">SPINRAZA is an example of an antisense medicine that modulates RNA splicing to increase protein production of the SMN protein (Figure 5), 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. There are a number of other diseases, including cystic fibrosis and Duchenne muscular dystrophy, which may be treated by modulating splicing using antisense technology.</div>
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<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Figure 5: Antisense medicine altering splicing of the SMN2 mRNA.</div>
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<div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We are also making progress in designing antisense medicines to target long, non-coding RNAs, or lncRNAs and RNAs that possess a toxic function in human diseases. Many of these RNAs, such as lncRNAs, do not make proteins but often cause disease by regulating the function of other genes or proteins. In 2014, we published a paper in <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Nature</span> in which we were the first to show that targeted reduction of a lncRNA with an antisense compound can ameliorate certain cognitive deficits in a mouse model of Angelman syndrome, or AS. Moreover, these studies demonstrate the potential therapeutic benefits of antisense medicines for the treatment of AS.</div>
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<div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Because the efficiency of our core technology platform can support multiple target-based antisense research programs, we can develop antisense medicines to target a broad range of diseases, efficiently producing a large and broad proprietary portfolio of medicines. We are currently pursuing antisense drug discovery programs focused on neurological, cardiometabolic, and other diseases.</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;">Collaborative Arrangements</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 established alliances with a cadre of leading global pharmaceutical companies. Our partners include the following companies, among others: AstraZeneca, Bayer, Biogen, GSK, Janssen, Novartis, Pfizer 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 2020, we recognized nearly $730 million in revenue, the majority of which was from our partnered medicines and programs. We have the potential to earn more than $20 billion in future milestone payments, licensing fees and other payments from our current partnerships, not including potential royalties. Below, we include the significant terms of our collaboration agreements. For additional details, including other financial information, see Note 6, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Collaborative Arrangements and Licensing Agreements,</span> in the Notes to the Consolidated Financial Statements.</div>
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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Strategic Partnership</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Biogen</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We have several strategic collaborations with Biogen focused on using antisense technology to advance the treatment of neurological disorders. These collaborations combine our expertise in creating antisense medicines with Biogen&#8217;s expertise in developing therapies for neurological disorders. We developed and licensed to Biogen SPINRAZA, our approved medicine to treat people with spinal muscular atrophy, or SMA. We and Biogen are currently developing eight investigational medicines to treat neurodegenerative diseases under these collaborations, including medicines in development to treat people with ALS, Alzheimer&#8217;s disease<sub>&#xA0;</sub>and Parkinson&#8217;s disease. In addition to these medicines, our collaborations with Biogen include a substantial research pipeline that addresses a broad range of neurological diseases. From inception through December 2020, we have received $2.8 billion from our Biogen collaborations.</div>
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<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Spinal Muscular Atrophy Collaborations</div>
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<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">SPINRAZA</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In January 2012, we entered into a collaboration agreement with Biogen to develop and commercialize SPINRAZA, an RNA-targeted therapy for the treatment of SMA. </span>SPINRAZA is approved in over 50 countries around the world. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">From inception through December 2020, we generated more than $</span>1.3<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> billion in total revenue under our SPINRAZA collaboration, including more than $930 million in revenue from SPINRAZA royalties and more than $435 million in R&amp;D revenue. 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. Biogen is responsible for global development, regulatory and commercialization activities and costs for SPINRAZA.</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;">New antisense medicines for the treatment of SMA</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In December 2017, we entered into a collaboration agreement with Biogen to </span>identify <span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">new antisense medicines for the treatment of SMA</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. </span><span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Biogen has the option to license therapies arising out of this collaboration following the completion of preclinical studies. Upon licensing, Biogen </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">will be responsible for global development, regulatory and commercialization activities and costs for such therapies</span><span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. Under the collaboration agreement, we received a </span>$25 million<span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> upfront payment in December 2017. We will receive development and regulatory milestone payments from Biogen if new medicines advance towards marketing approval. </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In total over the term of our collaboration, we are eligible to receive up to $1.2 billion in license fees, milestone payments and other payments. In addition, we are eligible to receive tiered royalties </span><span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">from the mid-teens to </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">mid-20 percent range </span><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></div>
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<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span>26</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 April 2018, we and Biogen entered into a strategic collaboration to develop novel antisense medicines for a broad range of neurological diseases and entered into a Stock Purchase Agreement, or SPA. As part of the collaboration, Biogen gained exclusive rights to the use of our antisense technology to develop therapies for these diseases for 10 years. We are responsible for the identification of antisense drug candidates based on selected targets</span>. Biogen is responsible for conducting IND-enabling toxicology studies for the selected medicine. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Biogen will have the option to license the selected medicine </span>after it completes the IND-enabling toxicology study. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">If Biogen exercises its option to license a medicine, it will assume global development, regulatory and commercialization responsibilities and costs for that medicine. </span><span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In the second quarter of 2018, we received </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$1 billion from Biogen, comprised of $</span>625<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million to purchase our stock at an approximately 25 percent cash premium and $375 million in an upfront payment. </span><span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We are eligible to receive up to $</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">270</span><span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million in milestone payments for each medicine that achieves marketing approval. </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In addition, we are eligible to receive tiered royalties </span><span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">up to the </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">20 percent range </span><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><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#xA0;</span><span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">W</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">e are advancing eight programs under this collaboration and through December 2020, we have generated over $1.05 billion in payments.</span></div>
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<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">2013 Strategic Neurology</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In September 2013, we and Biogen entered into a long-term strategic relationship focused on applying antisense technology to advance the treatment of neurodegenerative diseases. As part of the collaboration, Biogen gained exclusive rights to the use of our antisense technology to develop therapies for neurological diseases and has the option to license medicines resulting from this collaboration. We will usually be responsible for drug discovery and early development of antisense medicines and Biogen will have the option to license antisense medicines after Phase 2 proof-of-concept. In October 2016, we expanded our collaboration to include additional research activities we will perform. If Biogen exercises its option to license a medicine, it will assume global development, regulatory and commercialization responsibilities and costs for that medicine. We are currently advancing six investigational medicines in development under this collaboration, including a medicine for Parkinson&#8217;s disease, three medicines for ALS, a medicine for multiple system atrophy and a medicine for an undisclosed target. In December 2018, Biogen exercised its option to license our most advanced ALS medicine, tofersen, and as a result Biogen is now responsible for global development, regulatory and commercialization activities and costs for tofersen.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Under the terms of the agreement, we received an upfront payment of $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. For each antisense molecule that is chosen for drug discovery and development under this collaboration, we are eligible to receive up to approximately $260 million in a license fee and milestone payments per program. In addition, we are eligible to receive tiered royalties up to the mid-teens on net sales <span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">from any product that Biogen successfully commercializes under this collaboration</span>. Through December 2020, we have generated over $270 million under this collaboration, including $28 million we received from Biogen in 2020 when Biogen initiated Phase 1/2 trials for ION464, our investigational medicine for MSA and Parkinson&#8217;s disease and ION541, our investigational medicine for ALS.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">2012 Neurology</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In December 2012, we and Biogen entered into a collaboration agreement to develop and commercialize novel antisense medicines to treat neurodegenerative diseases. We are responsible for the development of each of the medicines through the completion of the initial Phase 2 clinical study for such medicine. Biogen has the option to license a medicine from each of the programs through the completion of the first Phase 2 study for each program. Under this collaboration, we are currently advancing IONIS-MAPT<sub>Rx</sub> for Alzheimer&#8217;s disease and ION582 for Angelman syndrome. If Biogen exercises its option to license a medicine, it will assume global development, regulatory and commercialization responsibilities and costs for that medicine. In December 2019, Biogen exercised its option to license IONIS-MAPT<sub>Rx</sub> and as a result Biogen is now 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;">Under the terms of the agreement, we received an upfront payment of $30 million. Over the term of the collaboration, we are eligible to receive up to $210 million in a license fee and milestone payments per program, plus a mark-up on the cost estimate of the Phase 1 and 2 studies. In addition, we are eligible to receive tiered royalties up to the mid-teens on net sales from any product that Biogen successfully commercializes under this collaboration. Through December 2020, we have generated over $155 million under our collaboration, including $19.5 million we received from Biogen for advancing IONIS-MAPT<sub>Rx </sub>during 2020.</div>
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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Research, Development and Commercialization Partners</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;">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 have two collaborations with AstraZeneca, one focused on the treatment of cardiovascular, renal and metabolic diseases and a second focused on the treatment of oncology diseases. We and AstraZeneca are currently developing several medicines under these collaborations, including medicines in development to treat people with cardiovascular disease, a genetically associated form of kidney disease, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">nonalcoholic steatohepatitis, or NASH, and cancer</span>. From inception through December 2020, we have generated more than $380 million from our AstraZeneca collaborations.</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;">Cardiovascular, Renal and Metabolic Diseases 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 July 2015, we and AstraZeneca formed a collaboration to discover and develop antisense therapies for treating cardiovascular, renal and metabolic diseases. Under our collaboration, AstraZeneca has licensed four medicines from us:</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;">ION449 (formerly IONIS-AZ4-2.5-L<sub>Rx</sub>), an investigational medicine we designed to reduce the liver production of PCSK9 and lower the plasma level of LDL-C and thus reduce the risk of cardiovascular disease;</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;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">ION532, an investigational medicine we designed to reduce the production of APOL1 for the </span>treatment of APOL1-associated chronic kidney disease;</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;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">ION839, an investigational medicine we designed to </span>inhibit the production of PNPLA3 protein, a major genetic determinant of NASH progression<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">; and</span></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;">ION455, an investigational medicine we designed as a potential treatment for NASH.</div></td>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">AstraZeneca is responsible for global development, regulatory and commercialization activities and costs for each of the medicines it has licensed and any medicines AstraZeneca licenses in the future.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Under the terms of the agreement, we received a $65 million upfront payment. We are eligible to receive license fees and milestone payments of up to more than $5.5 billion as medicines under this collaboration advance. 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. Through December 2020, we have generated over $235 million in payments, including $30 million we earned in 2020 when AstraZeneca licensed ION455 and $30 million in milestone payments we earned in 2020 when AstraZeneca advanced ION532 and ION449 in development.</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 2012, we entered into a collaboration agreement with AstraZeneca to discover and develop antisense medicines to treat cancer. We and AstraZeneca also established an oncology research program. AstraZeneca has the option to license medicines resulting from the program, and if AstraZeneca exercises its option to license a medicine, it will be responsible for global development, regulatory and commercialization activities and costs for such medicine. In 2020, AstraZeneca licensed ION736, an investigational medicine in development targeting FOXP3 for the treatment of cancer.</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 this agreement, we received $31 million in upfront payments. We are eligible to receive license fees and milestone payments of up to more than $265 million as this collaboration advances. 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. Through December 2020, we have generated over $140 million in payments under this collaboration, including $13 million we earned in 2020 when AstraZeneca licensed ION736</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 May 2015, we entered into an exclusive license agreement with Bayer to develop and commercialize IONIS-FXI<sub>Rx</sub> for the prevention of thrombosis and we received a $100 million upfront payment. In February 2017, we amended our agreement and Bayer licensed IONIS-FXI-L<sub>Rx</sub>. In conjunction with the amendment, we received a $75 million payment. In October 2019, Bayer decided it would advance IONIS-FXI-L<sub>Rx</sub> following positive clinical results. Bayer is now responsible for all global development, regulatory and commercialization activities and costs for the FXI program. We are eligible to receive additional milestone payments as the FXI program advances toward the market. Over the term of the collaboration, we are eligible to receive up to $385 million in license fees, milestone payments and other payments. In addition, we are eligible to receive tiered royalties in the low to high 20 percent range on gross margins of both medicines combined. Through December 2020, we have generated over $185 million under this collaboration.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In March 2010, we entered into an alliance with GSK using our antisense drug discovery platform to discover and develop new medicines against targets for serious and rare diseases, including infectious diseases and some conditions causing blindness. Under the collaboration, we received upfront payments of $35 million. Our collaboration with GSK covers hepatitis B virus, including IONIS-HBV<sub>Rx,</sub> which we designed to reduce the production of viral proteins associated with HBV infection. In the third quarter of 2019, following positive Phase 2 results, GSK licensed our HBV program. GSK is responsible for all global development, regulatory and commercialization activities and costs for the HBV program.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Under our agreement, if GSK successfully develops these medicines and achieves pre-agreed sales targets, we could receive license fees and milestone payments of up to $262 million. In addition, we are eligible to receive tiered royalties up to the mid-teens on net sales from any product that GSK successfully commercializes under this alliance. Through December 2020, we have generated over $185 million in payments under our collaboration.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Janssen Biotech, Inc.</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 2014, we entered into a collaboration agreement with Janssen Biotech, Inc. to discover and develop antisense medicines that can be locally administered, including oral delivery, to treat autoimmune disorders of the GI tract. Under our collaboration, Janssen is currently advancing ION253 for the treatment of immune-mediated GI disease. Janssen licensed ION253 in November 2017. Prior to Janssen&#8217;s license of ION253, we were responsible for the discovery activities to identify development candidates. Under our agreement, Janssen is responsible for global development, regulatory and commercialization activities and costs for ION253.</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 $35 million in upfront payments. In addition, we are eligible to receive tiered royalties up to the near teens on net sales <span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">from any product that Janssen successfully commercializes under this collaboration</span>. We are eligible to receive up to $285 million in <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">milestone payments and license fees </span>for ION253. Through December 2020, we have generated over $80 million under our collaboration, including $5 million we earned in the third quarter of 2020 when Janssen initiated a Phase 1 trial for ION253.</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;">Novartis</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In January 2017, we initiated a collaboration with Novartis to develop and commercialize pelacarsen. </span>We received a $75 million upfront payment in the first quarter of 2017. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In February 2019, Novartis licensed pelacarsen</span> and we earned a $150 million license fee. Novartis is responsible for conducting and funding future development and regulatory activities for pelacarsen, including a global Phase 3 cardiovascular outcomes study, which Novartis initiated in December 2019.<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#xA0;</span>In connection with Novartis&#8217; license of pelacarsen, we and Novartis established a more definitive framework under which the companies would negotiate the co-commercialization of pelacarsen in selected markets. Included in this framework is an option by which Novartis could solely commercialize pelacarsen in exchange for Novartis paying us increased sales milestone payments based on sales of pelacarsen.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Under the collaboration, we are eligible to receive up to $675 million in milestone payments related to pelacarsen. We are also eligible to receive tiered royalties in the mid-teens to low 20 percent range on net sales of pelacarsen. Through December 2020, w<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">e have generated approximately $250 million under our collaboration in upfront payments, milestone payments, license fees and other payments from 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;">In conjunction with this collaboration, we entered into a SPA with Novartis. As part of the SPA, Novartis purchased 1.6 million shares of our common stock for $100 million in the first quarter of 2017 and purchased $50 million of Akcea&#8217;s common stock at the IPO price concurrent with Akcea&#8217;s IPO in July 2017.</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;">Pfizer</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 October 2019, we entered into a license agreement with Pfizer for vupanorsen, an investigational medicine in development to treat people with certain cardiovascular diseases. We completed a Phase 2 study of vupanorsen in patients</span> with elevated levels of triglycerides, or hypertriglyceridemia, type 2 diabetes and <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">NAFLD. Pfizer is responsible for the global development, regulatory and commercialization activities for vupanorsen, subject to our right to co-commercialize in the U.S. and certain additional markets.</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;">Under the terms of the agreement, we received a $250 million upfront license fee. We are also eligible to receive development, regulatory and sales milestone payments of up to $1.3 billion and tiered royalties in the mid-teens to low 20 percent range on annual worldwide net sales. Prior to regulatory filing for marketing approval, we have the right, at our option to participate in certain commercialization activities with Pfizer in the U.S. and certain additional markets on pre-defined terms and based on meeting pre-defined criteria. </span>Through December 2020, w<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">e have generated over $330 million, including a $75 million milestone payment we earned in 2020 when Pfizer began the Phase 2b study of vupanorsen.</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;">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;">In August 2018, we entered into an exclusive license agreement with PTC to commercialize TEGSEDI and WAYLIVRA in Latin America and certain Caribbean countries. Under the license agreement, we are eligible to receive up to $26 million in payments. We are also eligible to receive royalties from PTC in the mid-20 percent range on net sales in Latin America and certain Caribbean countries for each medicine. PTC&#8217;s obligation to pay us royalties begins on the earlier of 12 months after the first commercial sale of a product in Brazil or the date that PTC recognizes revenue of at least $10 million in Latin America. Through December 2020, we have generated over $20 million under this collaboration.</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;">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 April 2013, we formed an alliance with Hoffman-La Roche Inc. and F. Hoffmann-La Roche Ltd., collectively Roche, to develop treatments for HD based on our antisense technology. Under the agreement, we discovered and developed tominersen, an investigational medicine targeting HTT protein. We developed tominersen through completion of our Phase 1/2 clinical study in people with early stage HD. In December 2017, upon completion of the Phase 1/2 study, Roche exercised its option to license tominersen<sub>&#xA0;</sub>and is now responsible for the global development, regulatory and commercialization activities and costs for tominersen.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Under the terms of the agreement, we received an upfront payment of $30 million in April 2013. We are eligible to receive up to $365 million in a license fee and milestone payments as tominersen advances. In addition, we are eligible to receive up to $136.5 million in milestone payments for each additional medicine successfully developed. We are also eligible to receive tiered royalties up to the mid-teens on net sales from any product resulting from this alliance. Through December 2020, we have generated $150 million under our collaboration.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><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;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In October 2018, we entered into a collaboration agreement with Roche to</span><span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> develop IONIS-FB-L</span><sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> for the treatment of complement-mediated diseases. We are currently conducting Phase 2 studies in two disease indications for </span><span style="background-color: #FBFBFB; 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;">, one for the treatment of patients with GA, the advanced stage of dry AMD, and a second for the treatment of patients with IgA nephropathy. </span>Roche<span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> has the option to license 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;"> at the completion of these studies. Upon licensing, </span>Roche <span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">will be responsible for global development, regulatory and commercialization activities and 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;"><span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Under the terms of this agreement, we received a </span>$75 million<span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> upfront payment in October 2018. We are eligible to receive up to </span>$684 million<span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> in milestone payments and license fees. In addition, we are also eligible to receive tiered royalties from the high teens to </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">twenty percent</span><span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> on net sales. </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Through December 2020, we have generated over $75 million under our 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;">Other Agreements</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;">Alnylam Pharmaceuticals, Inc.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Under the terms of our agreement with Alnylam, we exclusively licensed to Alnylam our patent estate relating to antisense motifs and mechanisms and oligonucleotide chemistry for double-stranded RNAi therapeutics in exchange for 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 rights to 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 medicines 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>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In the fourth quarter of 2020, we completed an arbitration process with Alnylam. The arbitration panel awarded us $41 million for payments owed to us by Alnylam related to Alnylam&#8217;s agreement with Sanofi Genzyme. We recognized the $41 million payment from Alnylam as R&amp;D revenue in the fourth quarter of 2020.</div>
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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;">The Ludwig Institute; Center for Neurological Studies</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 a collaboration with the Ludwig Institute, the Center for Neurological Studies and researchers to discover and develop antisense medicines for ALS and other neurodegenerative diseases. Under this agreement, we agreed to pay the Ludwig Institute and the Center for Neurological Studies modest milestone payments and royalties on any antisense medicines resulting from the collaboration.</div>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Manufacturing</div>
<div style="text-align: justify;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> </span><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We manufacture most of the drug product we use for our research and development activities ourselves. We have also manufactured 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 antisense 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>
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<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>
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<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 materials and/or commercial supply for our partners. For example, in the past we have manufactured clinical supply materials for AstraZeneca, Bayer, Biogen, GSK and Novartis and commercial supply materials for Biogen.</div>
<div style="text-align: justify; text-indent: 36pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> </span><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We believe we have sufficient manufacturing capacity at our own facility or at contract manufacturing organizations, or CMOs, to meet our current internal research, development and potential commercial needs, as well as our obligations under existing agreements with our partners for research, development and commercial needs. We believe our current network of CMO partners are capable of providing sufficient quantities to meet anticipated commercial demands. Additionally, we continue to evaluate relationships with additional suppliers to increase overall capacity and diversify our supply chain. While we believe that there are alternate sources of supply that can satisfy our commercial requirements, it is possible that identifying and establishing relationships with such sources, if necessary, could result in significant delay or material additional costs. We also could experience a disruption in supply from our current CMO partners.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">CMOs are subject to the FDA&#8217;s cGMP requirements and other rules and regulations prescribed by foreign regulatory authorities. We depend on our CMO partners for continued compliance with cGMP requirements and applicable foreign standards.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Specifically, we have the following in place for our approved medicines, SPINRAZA, TEGSEDI and WAYLIVRA and our medicines in Phase 3 development: tominersen, tofersen, pelacarsen, IONIS-TTR-L<sub>Rx</sub> and IONIS-APOCIII-L<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; 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;">Since September 2018, Biogen has provided SPINRAZA drug supply. Biogen has an oligonucleotide synthesis manufacturing facility that gives it the capability to manufacture SPINRAZA.</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;">TEGSEDI and WAYLIVRA</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">For TEGSEDI&#8217;s commercial drug supply, we are using CMOs to produce custom raw materials, active pharmaceutical ingredient, or API, and finished goods. For WAYLIVRA&#8217;s commercial drug supply, we have manufactured custom raw materials and API. We are using CMOs to produce the finished goods for WAYLIVRA. Our CMO partners have extensive technical expertise and cGMP experience. We believe our current network of CMO partners are capable of providing sufficient quantities to meet anticipated commercial demands.</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;">Tominersen</div>
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<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Pursuant to our collaboration with Roche, Roche is responsible for tominersen drug supply.</div>
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<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Tofersen</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We provided Biogen with the first batch of API for tofersen in 2015 to support the first in human studies under our collaboration agreement with Biogen. Pursuant to our collaboration with Biogen, Biogen is responsible for tofersen drug supply. Biogen has an oligonucleotide synthesis manufacturing facility that gives it the capability to manufacture tofersen for all subsequent clinical studies and potential commercialization, including providing the API for the current Phase 3 study.</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;">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 supplied the API and the finished drug product for pelacarsen&#8217;s Phase 3 study. Pursuant to our collaboration with Novartis, Novartis is responsible for any further pelacarsen drug supply.</div>
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<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Wholly Owned Phase 3 Medicines: IONIS-TTR-L<sub>Rx</sub>,<sub>&#xA0;</sub>IONIS-APOCIII-L<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;">We have supplied the API and the finished drug product for </span>IONIS-TTR-L<sub>Rx</sub> and IONIS-APOCIII-L<sub>Rx</sub> 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. We plan to leverage our relationships with CMOs to procure long-term raw material and drug supplies at competitive prices in the future.</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;">LICA Medicines</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We have manufactured and used CMOs to manufacture our LICA medicines for our preclinical and clinical studies. LICA enables lower doses than unconjugated oligonucleotides. With our expertise in optimizing manufacturing of oligonucleotides, we believe we can scale up manufacturing of our LICA medicines at commercially competitive prices or use CMO&#8217;s.</div>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Patents and Proprietary Rights</div>
<div style="text-align: justify;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> </span><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our success depends, in part, on our ability to obtain patent protection for our products in the U.S. and other countries. We own or have exclusively licensed a substantial patent estate with numerous issued patents worldwide protecting our products and, more generally, our platform for development and commercialization of oligonucleotide therapeutics. We focus our resources on patents and new patent applications that drive value for our company.</div>
<div style="text-align: left; text-indent: 36pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> </span><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We own or control patents that provide exclusivity for products in our pipeline and patents that provide exclusivity for our core technology in the field of antisense more generally. Our core technology patents include claims to chemically modified nucleosides and oligonucleotides as well as antisense medicine designs utilizing these chemically modified nucleosides. These core claims are independent of specific therapeutic target, nucleic acid sequence, or clinical indication. We also own a large number of patents claiming antisense compounds having nucleic acid sequences complementary to therapeutic target nucleic acids, independent of the particular chemical modifications incorporated into the antisense compound. Most importantly, we seek and obtain issued patent claims to specifically protect each of our medicines. For example, we file and seek to obtain claims covering each drug&#8217;s nucleic acid sequence and precise drug design. In sum, we maintain our competitive advantage in the field of antisense technology by protecting our core platform technology and by creating multiple layers of patent protection for each of our specific medicines in development.</div>
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    <td style="width: 74.42%; vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Type of Patent Claim</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(Broadly Applicable to Specific)</div></td>
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    <td style="width: 23.09%; vertical-align: bottom;">&#160;</td>
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    <td style="width: 74.42%; vertical-align: top;"><div style="text-align: left; text-indent: -18pt; margin-left: 52.8pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#9679;</span><span style="display: inline-block; text-indent: 0px; font-size: 1px; width: 18pt">&#xA0;</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Chemically Modified Nucleosides and Oligonucleotides (target and sequence independent)</span></div><div style="text-align: left; text-indent: -18pt; margin-left: 52.8pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#9679;</span><span style="display: inline-block; text-indent: 0px; font-size: 1px; width: 18pt">&#xA0;</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Antisense Drug Design Motifs (target and sequence independent)</span></div><div style="text-align: left; text-indent: -18pt; margin-left: 52.8pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#9679;</span><span style="display: inline-block; text-indent: 0px; font-size: 1px; width: 18pt">&#xA0;</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Therapeutic Methods (sequence and chemistry independent)</span></div><div style="text-align: left; text-indent: -18pt; margin-left: 52.8pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#9679;</span><span style="display: inline-block; text-indent: 0px; font-size: 1px; width: 18pt">&#xA0;</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Antisense Sequence (chemistry independent)</span></div><div style="text-align: left; text-indent: -18pt; margin-left: 52.8pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#9679;</span><span style="display: inline-block; text-indent: 0px; font-size: 1px; width: 18pt">&#xA0;</span><span style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Drug Composition</span></div></td>
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    <td style="width: 23.09%; vertical-align: top;"><div style="text-align: center;"><img src="image00018.jpg" width="115" height="129" alt="graphic" /></div></td>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><span style="text-decoration: underline;">Chemically Modified Nucleosides and Oligonucleotides</span></div>
<div style="text-align: justify; text-indent: 36pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> </span><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The most broadly applicable of our patents are those that claim modified nucleosides and oligonucleotides comprising the modified nucleosides that we incorporate into our antisense medicines to increase their therapeutic efficacy. Nucleosides and chemically modified nucleosides are the basic building blocks of our antisense medicines. Therefore claims that cover any oligonucleotide incorporating one of our proprietary modified nucleosides can apply to a wide array of antisense mechanisms of action as well as several therapeutic targets. Of particular note are our patents covering our proprietary 2&#8217;-O-(2-methoxy) ethyl, or &#8220;MOE,&#8221; modified nucleosides, incorporated into many of our second-generation development compounds, as well as our constrained-ethyl nucleosides, or &#8220;cEt&#8221; nucleosides incorporated into our Generation 2.5 compounds. The following are some of our patents in this category in key jurisdictions (U.S., Europe and Japan):</div>
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    <td style="width: 16.86%; vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Jurisdiction</div></td>
    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>
    <td style="width: 11.11%; vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Patent No.</div></td>
    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>
    <td style="width: 27.72%; vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Title</div></td>
    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>
    <td style="width: 12.82%; vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Expiration</div></td>
    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>
    <td style="width: 24.82%; vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Description of Claims</div></td>
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    <td style="width: 16.86%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">United States</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 11.11%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">7,101,993</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 27.72%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">OLIGONUCLEOTIDES CONTAINING 2&#8217;-O-MODIFIED PURINES</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 12.82%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2023</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 24.82%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Certain MOE nucleosides and oligonucleotides containing these nucleotides</div></td>
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    <td style="width: 16.86%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">United States</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 11.11%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">7,399,845</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 27.72%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6-MODIFIED BICYCLIC NUCLEIC ACID ANALOGS</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 12.82%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2027</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 24.82%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">cEt nucleosides and oligonucleotides containing these nucleoside analogs</div></td>
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    <td style="width: 16.86%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">United States</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 11.11%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">7,741,457</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 27.72%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6-MODIFIED BICYCLIC NUCLEIC ACID ANALOGS</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 12.82%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2027</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 24.82%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">cEt nucleosides and oligonucleotides containing these nucleoside analogs</div></td>
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    <td style="width: 16.86%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">United States</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 11.11%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">8,022,193</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 27.72%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6-MODIFIED BICYCLIC NUCLEIC ACID ANALOGS</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 12.82%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2027</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 24.82%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Oligonucleotides containing cEt nucleoside analogs</div></td>
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    <td style="width: 16.86%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Europe</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 11.11%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1984381</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 27.72%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6-MODIFIED BICYCLIC NUCLEIC ACID ANALOGS</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 12.82%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2027</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 24.82%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">cEt nucleosides and oligonucleotides containing these nucleoside analogs</div></td>
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    <td style="width: 16.86%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Europe</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 11.11%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2314594</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 27.72%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6-MODIFIED BICYCLIC NUCLEIC ACID ANALOGS</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 12.82%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2027</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 24.82%; vertical-align: top; background-color: #FFFFFF;"><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>
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    <td style="width: 16.86%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Japan</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 11.11%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">5342881</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 27.72%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6-MODIFIED BICYCLIC NUCLEIC ACID ANALOGS</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 12.82%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2027</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 24.82%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">cEt nucleosides and oligonucleotides containing these nucleoside analogs</div></td>
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    <td style="width: 16.86%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">United States</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 11.11%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">7,569,686</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 27.72%; vertical-align: top; background-color: #FFFFFF;"><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: 12.82%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2027</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 24.82%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Methods of synthesizing cEt nucleosides</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-weight: bold;"><span style="text-decoration: underline;">Antisense Drug Design Motifs</span></div>
<div style="text-align: justify; text-indent: 36pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> </span><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We also have patents that claim oligonucleotides comprising antisense drug design motifs, or patterns of nucleoside modifications at specified positions in the oligonucleotide. Patent claims covering our antisense drug design motifs are independent of nucleic acid sequence, so they cover oligonucleotides having the recited motif, regardless of cellular target or clinical indication. The claimed motifs generally confer properties that optimize oligonucleotides for a particular antisense mechanism of action, such as ribonuclease H (RNase H), RNAi, or splicing. We have designed oligonucleotides incorporating motifs, which we refer to as chimeric compounds or gapmers, to exploit the RNase H mechanism to achieve target RNA reduction. Almost all of our medicines in clinical development, including TEGSEDI and WAYLIVRA, but excluding SPINRAZA, contain this gapmer antisense drug design motif. We own a U.S. patent that covers all of our second-generation MOE gapmer antisense medicines until March of 2023.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In addition, we have patent claims to antisense drug design motifs incorporating bicyclic nucleosides, which include both locked nucleic acids, or &#8220;LNA&#8221; and cEt. In Europe, we have been granted claims drawn to certain gapmer oligonucleotides with bicyclic nucleosides, which include locked nucleic acids in the wings. We have also successfully obtained issued patent claims covering our Generation 2.5 gapmer antisense drug design motifs that incorporate our cEt modified nucleosides. The following patents are some examples of our issued patents in this category in key jurisdictions (U.S., Europe and Japan):</div>
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    <td style="width: 16.86%; vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Jurisdiction</div></td>
    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>
    <td style="width: 12.5%; 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;">Patent No.</div></td>
    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>
    <td style="width: 27.72%; vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Title</div></td>
    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>
    <td style="width: 12.82%; vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Expiration</div></td>
    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>
    <td style="width: 23.43%; vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Description of Claims</div></td>
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    <td style="width: 16.86%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">United States</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 12.5%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">7,015,315</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 27.72%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">GAPPED OLIGONUCLEOTIDES</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 12.82%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2023</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 23.43%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Gapmer oligonucleotides having 2&#8217;-O-alkyl-O-alkyl nucleosides</div></td>
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    <td style="width: 16.86%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">United States</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 12.5%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">7,750,131</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 27.72%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">5&#8217;-MODIFIED BICYCLIC NUCLEIC ACID ANALOGS</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 12.82%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2027</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 23.43%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Oligonucleotides having 5&#8217;-methyl BNA nucleosides</div></td>
  </tr>
  <tr>
    <td style="width: 16.86%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Europe</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 12.5%; vertical-align: top; background-color: #CCEEFF;"><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: 27.72%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">ANTISENSE COMPOUNDS</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 12.82%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2027</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 23.43%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Gapmer oligonucleotides having 2&#8217;-modifed and LNA nucleosides</div></td>
  </tr>
  <tr>
    <td style="width: 16.86%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Europe</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 12.5%; vertical-align: top; background-color: #FFFFFF;"><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: 27.72%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">ANTISENSE COMPOUNDS</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 12.82%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2027</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 23.43%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Gapmer oligonucleotides having wings comprised of 2&#8217;-MOE and bicyclic nucleosides</div></td>
  </tr>
  <tr>
    <td style="width: 16.86%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Europe</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 12.5%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2410054</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 27.72%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">ANTISENSE COMPOUNDS</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 12.82%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2027</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 23.43%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Gapmer oligonucleotides having a 2&#8217;-modifed nucleoside in the 5&#8217;-wing and a bicyclic nucleoside in the 3&#8217;-wing</div></td>
  </tr>
  <tr>
    <td style="width: 16.86%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Japan</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 12.5%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">5665317</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 27.72%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">ANTISENSE COMPOUNDS</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 12.82%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2027</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 23.43%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Gapmer oligonucleotides having wings comprised of 2&#8217;-MOE and bicyclic nucleosides</div></td>
  </tr>
  <tr>
    <td style="width: 16.86%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">United States</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 12.5%; vertical-align: top; background-color: #CCEEFF;"><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: #CCEEFF;">&#160;</td>
    <td style="width: 27.72%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">ANTISENSE COMPOUNDS</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 12.82%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2028</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 23.43%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Gapmer oligonucleotides having BNA nucleosides and 2&#8217;-MOE nucleosides</div></td>
  </tr>
  <tr>
    <td style="width: 16.86%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">United States</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 12.5%; vertical-align: top; background-color: #FFFFFF;"><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: #FFFFFF;">&#160;</td>
    <td style="width: 27.72%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">ANTISENSE COMPOUNDS</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 12.82%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2028</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 23.43%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Gapmer oligonucleotides having BNA nucleosides and 2&#8217;-MOE nucleosides and/or 2&#8217;-OMe nucleosides</div></td>
  </tr>
  <tr>
    <td style="width: 16.86%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Europe</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 12.5%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3067421</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 27.72%; vertical-align: top; background-color: #CCEEFF;"><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: #CCEEFF;">&#160;</td>
    <td style="width: 12.82%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2032</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 23.43%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Gapmer oligonucleotides having at least one bicyclic, one 2&#8217;-modified nucleoside and one 2&#8217;-deoxynucleoside</div></td>
  </tr>
</table>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><span style="text-decoration: underline;">LIgand-Conjugated Antisense (LICA) Technology</span></div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We also have patent claims to new chemistries created to enhance targeting of antisense medicines to specific tissues and cells to improve a drug&#8217;s properties. We designed our N-acetyl-galactosamine, or 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 cellpadding="0" cellspacing="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" id="zafb86c43873d4b8fa95369c03742f16a">
  <tr>
    <td style="width: 16.86%; vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Jurisdiction</div></td>
    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>
    <td style="width: 11.11%; vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Patent</div></td>
    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>
    <td style="width: 26.94%; vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Title</div></td>
    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>
    <td style="width: 12.82%; vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Expiration</div></td>
    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>
    <td style="width: 25.6%; vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Description of Claims</div></td>
  </tr>
  <tr>
    <td style="width: 16.86%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">United States</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 11.11%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">9,127,276</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 26.94%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">CONJUGATED ANTISENSE COMPOUNDS AND THEIR USE</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 12.82%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2034</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 25.6%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Preferred THA LICA conjugated to any group of nucleosides, including gapmers, double-stranded siRNA compounds, and fully modified oligonucleotides</div></td>
  </tr>
  <tr>
    <td style="width: 16.86%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">United States</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 11.11%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">9,181,549</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 26.94%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">CONJUGATED ANTISENSE COMPOUNDS AND THEIR USE</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 12.82%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2034</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 25.6%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Preferred THA conjugate having our preferred linker and cleavable moiety conjugated to any oligomeric compound or any nucleoside having a 2&#8217;-MOE modification or a cEt modification</div></td>
  </tr>
  <tr>
    <td style="width: 16.86%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Europe</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 11.11%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2991661</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 26.94%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">CONJUGATED ANTISENSE COMPOUNDS AND THEIR USE</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 12.82%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2034</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 25.6%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Preferred THA LICA conjugated to any group of nucleosides, including gapmers, double-stranded siRNA compounds, and fully modified oligonucleotides</div></td>
  </tr>
</table>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><span style="text-decoration: underline;">Therapeutic Methods of Treatment and Antisense Drug Sequences</span></div>
<div style="text-align: justify; text-indent: 36pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> </span><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In addition to our broad core patents, we also own hundreds of patents, worldwide, with claims to antisense compounds having particular sequences and compounds directed to particular therapeutically important targets or methods of achieving cellular or clinical endpoints using these antisense compounds. These &#8220;Target&#8221; patents also include claims reciting the specific nucleic acid sequences utilized by our products, independent of chemical modifications and motifs. In addition, our product-specific patents typically include claims combining specific nucleic acid sequences with nucleoside modifications and motifs. In this way, we seek patent claims narrowly tailored to protect our products specifically, in addition to the broader core antisense patents described above.</div>
<div><br /></div>
<div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
<div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span>34</span></div>
</div>
<div style="page-break-after:always;"><hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>
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</div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">SPINRAZA and Survival Motor Neuron</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We believe SPINRAZA is protected from generic competition in the U.S. and Europe until at least 2030 by a suite of patents. These issued patents include: (i) patents licensed from the University of Massachusetts drawn to antisense compounds having the sequence of SPINRAZA, independent of chemical modification and uses of such compounds for treating SMA, and (ii) joint patents with Cold Spring Harbor Laboratory claiming fully modified 2&#8217;MOE compositions targeting SMN2, including the precise composition of matter of SPINRAZA and methods of using such compositions. We have filed for patent term extension, to potentially extend the term beyond 2030. With Biogen&#8217;s license of SPINRAZA, we assigned our interest in these patents to Biogen. The table below lists some key issued patents protecting SPINRAZA in the U.S. and Europe:</div>
<div><br /></div>
<table cellpadding="0" cellspacing="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" id="z9838c803f1fa4f799ba4e276184ec3f4">
  <tr>
    <td style="width: 16.86%; vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Jurisdiction</div></td>
    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>
    <td style="width: 12.5%; 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;">Patent No.</div></td>
    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>
    <td style="width: 26.4%; vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Title</div></td>
    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>
    <td style="width: 12.82%; vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Expiration</div></td>
    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>
    <td style="width: 24.75%; vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Description of Claims</div></td>
  </tr>
  <tr>
    <td style="width: 16.86%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">United States</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 12.5%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10,266,822</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 26.4%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">SPINAL MUSCULAR ATROPHY (SMA) TREATMENT VIA TARGETING OF SMN2 SPLICE SITE INHIBITORY SEQUENCES</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 12.82%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2025</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 24.75%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Methods of increasing exon-7 containing SMN2 mRNA in a cell using an oligonucleotide having the sequence of SPINRAZA</div></td>
  </tr>
  <tr>
    <td style="width: 16.86%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">United States</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 12.5%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">8,110,560</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 26.4%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">SPINAL MUSCULAR ATROPHY (SMA) TREATMENT VIA TARGETING OF SMN2 SPLICE SITE INHIBITORY SEQUENCES</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 12.82%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2025</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 24.75%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Methods of using antisense oligonucleotides having sequence of SPINRAZA to alter splicing of SMN2 and/or to treat SMA</div></td>
  </tr>
  <tr>
    <td style="width: 16.86%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Europe</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 12.5%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1910395</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 26.4%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">COMPOSITIONS AND METHODS FOR MODULATION OF SMN2 SPLICING</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 12.82%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2026</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 24.75%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Sequence and chemistry (full 2&#8217;-MOE) of SPINRAZA</div></td>
  </tr>
  <tr>
    <td style="width: 16.86%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Europe</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 12.5%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3308788</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 26.4%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">COMPOSITIONS AND METHODS FOR MODULATION OF SMN2 SPLICING</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 12.82%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2026</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 24.75%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Pharmaceutical compositions that include SPINRAZA</div></td>
  </tr>
  <tr>
    <td style="width: 16.86%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">United States</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 12.5%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">7,838,657</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 26.4%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">SPINAL MUSCULAR ATROPHY (SMA) TREATMENT VIA TARGETING OF SMN2 SPLICE SITE INHIBITORY SEQUENCES</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 12.82%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2027</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 24.75%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Oligonucleotides having sequence of SPINRAZA</div></td>
  </tr>
  <tr>
    <td style="width: 16.86%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">United States</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 12.5%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">8,361,977</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 26.4%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">COMPOSITIONS AND METHODS FOR MODULATION OF SMN2 SPLICING</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 12.82%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2030</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 24.75%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Sequence and chemistry (full 2&#8217;-MOE) of SPINRAZA</div></td>
  </tr>
  <tr>
    <td style="width: 16.86%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">United States</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 12.5%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">8,980,853</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 26.4%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">COMPOSITIONS AND METHODS FOR MODULATION OF SMN2 SPLICING IN A SUBJECT</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 12.82%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2030</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 24.75%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Methods of administering SPINRAZA</div></td>
  </tr>
  <tr>
    <td style="width: 16.86%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">United States</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 12.5%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">9,717,750</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 26.4%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">COMPOSITIONS AND METHODS FOR MODULATION OF SMN2 SPLICING IN A SUBJECT</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 12.82%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2030</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 24.75%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Methods of administering SPINRAZA to a patient</div></td>
  </tr>
  <tr>
    <td style="width: 16.86%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Europe</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 12.5%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3449926</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 26.4%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">COMPOSITIONS AND METHODS FOR MODULATION OF SMN2 SPLICING IN A SUBJECT</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 12.82%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2030</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 24.75%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Pharmaceutical compositions that include SPINRAZA for treating SMA</div></td>
  </tr>
  <tr>
    <td style="width: 16.86%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Europe</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 12.5%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3305302</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 26.4%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">COMPOSITIONS AND METHODS FOR MODULATION OF SMN2 SPLICING IN A SUBJECT</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 12.82%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2030</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 24.75%; vertical-align: top; background-color: #FFFFFF;"><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>
</table>
<div style="text-align: left;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> </span><br /></div>
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<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span>35</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;">TEGSEDI and Transthyretin</div>
<div style="text-align: justify;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> </span><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We believe TEGSEDI is protected from generic competition in the U.S. and Europe until at least 2031. Additional patent applications designed to protect TEGSEDI in other foreign jurisdictions are being pursued. The table below lists some key issued patents protecting TEGSEDI<sub>&#xA0;</sub>in the U.S. and Europe:</div>
<div><br /></div>
<table cellpadding="0" cellspacing="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" id="zccaf71e1a65e4cbeacb189e3b10b53e7">
  <tr>
    <td style="width: 16.86%; vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Jurisdiction</div></td>
    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>
    <td style="width: 11.11%; vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Patent No.</div></td>
    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>
    <td style="width: 26.96%; vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Title</div></td>
    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>
    <td style="width: 12.82%; vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Expiration</div></td>
    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>
    <td style="width: 25.58%; vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Description of Claims</div></td>
  </tr>
  <tr>
    <td style="width: 16.86%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">United States</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 11.11%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">8,101,743</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 26.96%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">MODULATION OF TRANSTHYRETIN EXPRESSION</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 12.82%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2025</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 25.58%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Antisense sequence and chemistry of TEGSEDI</div></td>
  </tr>
  <tr>
    <td style="width: 16.86%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">United States</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 11.11%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">8,697,860</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 26.96%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">DIAGNOSIS AND TREATMENT OF DISEASE</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 12.82%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2031</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 25.58%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Composition of TEGSEDI</div></td>
  </tr>
  <tr>
    <td style="width: 16.86%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">United States</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 11.11%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">9,061,044</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 26.96%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">MODULATION OF TRANSTHYRETIN EXPRESSION</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 12.82%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2031</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 25.58%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Sodium salt composition of TEGSEDI</div></td>
  </tr>
  <tr>
    <td style="width: 16.86%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">United States</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 11.11%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">9,399,774</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 26.96%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">MODULATION OF TRANSTHYRETIN EXPRESSION</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 12.82%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2031</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 25.58%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Methods of treating transthyretin amyloidosis by administering TEGSEDI</div></td>
  </tr>
  <tr>
    <td style="width: 16.86%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Europe</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 11.11%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2563920</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 26.96%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">MODULATION OF TRANSTHYRETIN EXPRESSION</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 12.82%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2031</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 25.58%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Composition of TEGSEDI</div></td>
  </tr>
</table>
<div style="text-align: left; text-indent: 36pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> </span><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">WAYLIVRA and Apolipoprotein C-III</div>
<div style="text-align: justify; text-indent: 36pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> </span><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We have obtained patent claims in the U.S. and Europe drawn to the use of antisense compounds complementary to a broad active region of human ApoC-III, including the site targeted by WAYLIVRA. We have also obtained issued patents claiming the specific sequence and chemical composition of WAYLIVRA in the U.S. and Europe. We believe the issued claims protect WAYLIVRA from generic competition in the U.S. and Europe until at least 2023 and 2024, respectively. We are pursuing additional patent applications designed to protect WAYLIVRA worldwide. The table below lists some key issued patents protecting WAYLIVRA in the U.S. and Europe:</div>
<div><br /></div>
<table cellpadding="0" cellspacing="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" id="zea39a725ff9c40f78edac455a3047283">
  <tr>
    <td style="width: 16.86%; vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Jurisdiction</div></td>
    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>
    <td style="width: 11.11%; vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Patent No.</div></td>
    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>
    <td style="width: 26.65%; vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Title</div></td>
    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>
    <td style="width: 12.82%; vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Expiration</div></td>
    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>
    <td style="width: 25.89%; vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Description of Claims</div></td>
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  <tr>
    <td style="width: 16.86%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">United States</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 11.11%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">9,624,496</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 26.65%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">MODULATION OF APOLIPOPROTEIN C-III EXPRESSION</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 12.82%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2023</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 25.89%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Antisense compounds specifically hybridizable within the nucleotide region of ApoCIII targeted by WAYLIVRA</div></td>
  </tr>
  <tr>
    <td style="width: 16.86%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">United States</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 11.11%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">7,598,227</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 26.65%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">MODULATION OF APOLIPOPROTEIN C-III EXPRESSION</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 12.82%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2023</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 25.89%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Methods of treating hyperlipidemia, lowering cholesterol levels or lowering triglyceride levels with WAYLIVRA</div></td>
  </tr>
  <tr>
    <td style="width: 16.86%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">United States</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 11.11%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">7,750,141</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 26.65%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">MODULATION OF APOLIPOPROTEIN C-III EXPRESSION</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 12.82%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2023</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 25.89%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Antisense sequence and chemistry of WAYLIVRA</div></td>
  </tr>
  <tr>
    <td style="width: 16.86%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Europe</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 11.11%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1622597</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 26.65%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">MODULATION OF APOLIPOPROTEIN C-III EXPRESSION</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 12.82%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2024</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 25.89%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Antisense sequence and chemistry of WAYLIVRA</div></td>
  </tr>
  <tr>
    <td style="width: 16.86%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Europe</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 11.11%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2441449</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 26.65%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">MODULATION OF APOLIPOPROTEIN C-III EXPRESSION</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 12.82%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2024</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 25.89%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Antisense compounds specifically hybridizable within the nucleotide region of ApoCIII targeted by WAYLIVRA</div></td>
  </tr>
  <tr>
    <td style="width: 16.86%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Europe</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 11.11%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3002007</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 26.65%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">MODULATION OF APOLIPOPROTEIN C-III EXPRESSION</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 12.82%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2024</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 25.89%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Compounds complementary to an ApoCIII nucleic acid for use in therapy</div></td>
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    <td style="width: 16.86%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">United States</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 11.11%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">9,157,082</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 26.65%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">MODULATION OF APOLIPOPROTEIN C-III (APOCIII) EXPRESSION</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 12.82%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2032</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 25.89%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Methods of using ApoCIII antisense oligonucleotides for reducing pancreatitis and chylomicronemia and increasing HDL</div></td>
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  <tr>
    <td style="width: 16.86%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">United States</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 11.11%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">9,593,333</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 26.65%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">MODULATION OF APOLIPOPROTEIN C-III (APOCIII) EXPRESSION IN LIPOPROTEIN LIPASE DEFICIENT (LPLD) POPULATIONS</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 12.82%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2034</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 25.89%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Methods of treating lipoprotein lipase deficiency with an ApoCIII specific inhibitor wherein triglyceride levels are reduced</div></td>
  </tr>
  <tr>
    <td style="width: 16.86%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Europe</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 11.11%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2956176</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 26.65%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">MODULATION OF APOLIPOPROTEIN C-III (APOCIII) EXPRESSION IN LIPOPROTEIN LIPASE DEFICIENT (LPLD) POPULATIONS</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 12.82%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2034</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 25.89%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">ApoCIII specific inhibitors including WAYLIVRA for treating lipoprotein lipase deficiency or familial chylomicronemia syndrome</div></td>
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</table>
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<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span>36</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;">Tominersen and Huntingtin</div>
<div style="text-align: justify;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> </span><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We believe tominersen is protected from generic competition in the U.S. and Europe until at least 2030. Additional patent applications designed to protect tominersen in other foreign jurisdictions are being pursued. The table below lists some key issued patents protecting tominersen<sub>&#xA0;</sub>in the U.S. and Europe:</div>
<div><br /></div>
<table cellpadding="0" cellspacing="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" id="z38765f7950a14836ae8dce880b49fb41">
  <tr>
    <td style="width: 16.86%; vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Jurisdiction</div></td>
    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>
    <td style="width: 11.11%; vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Patent No.</div></td>
    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>
    <td style="width: 26.96%; vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Title</div></td>
    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>
    <td style="width: 12.82%; vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Expiration</div></td>
    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>
    <td style="width: 25.58%; vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Description of Claims</div></td>
  </tr>
  <tr>
    <td style="width: 16.86%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">United States</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 11.11%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">7,951,934</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 26.96%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">COMPOSITIONS AND THEIR USES DIRECTED TO HUNTINGTIN</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 12.82%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2027</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 25.58%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Antisense sequence of tominersen</div></td>
  </tr>
  <tr>
    <td style="width: 16.86%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">United States</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 11.11%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">8,952,145</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 26.96%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">COMPOSITIONS AND THEIR USES DIRECTED TO HUNTINGTIN</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 12.82%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2027</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 25.58%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Antisense compound specifically hybridizable within the nucleotide region of HTT targeted by tominersen</div></td>
  </tr>
  <tr>
    <td style="width: 16.86%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Europe</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 11.11%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2161038</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 26.96%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">COMPOSITIONS AND THEIR USES DIRECTED TO HUNTINGTIN</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 12.82%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2027</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 25.58%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Antisense sequence of tominersen</div></td>
  </tr>
  <tr>
    <td style="width: 16.86%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">United States</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 11.11%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">9,273,315</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 26.96%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">MODULATION OF HUNTINGTIN EXPRESSION</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 12.82%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2030</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 25.58%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Composition of tominersen</div></td>
  </tr>
  <tr>
    <td style="width: 16.86%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">United States</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 11.11%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">8,906,873</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 26.96%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">MODULATION OF HUNTINGTIN EXPRESSION</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 12.82%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2030</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 25.58%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Methods of treating Huntington&#8217;s disease by administering tominersen</div></td>
  </tr>
  <tr>
    <td style="width: 16.86%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Europe</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 11.11%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2475675</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 26.96%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">MODULATION OF HUNTINGTIN EXPRESSION</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 12.82%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2030</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 25.58%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Composition of tominersen</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;">Tofersen and SOD-1</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We believe tofersen is protected from generic competition in the U.S. and Europe until at least 2035. Additional patent applications designed to protect tofersen in other foreign jurisdictions are being pursued. With Biogen&#8217;s license of tofersen, we assigned our interest in these patents to Biogen. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">The table below lists some key issued patents protecting t</span>ofersen in the U.S. and Europe:</div>
<div><br /></div>
<table cellpadding="0" cellspacing="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" id="z123fad188c6749f183b2ae904ee76ddd">
  <tr>
    <td style="width: 16.86%; vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Jurisdiction</div></td>
    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>
    <td style="width: 12.5%; 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;">Patent No.</div></td>
    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>
    <td style="width: 26.43%; vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Title</div></td>
    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>
    <td style="width: 12.82%; vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Expiration</div></td>
    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>
    <td style="width: 24.72%; vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Description of Claims</div></td>
  </tr>
  <tr>
    <td style="width: 16.86%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">United States</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 12.5%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">8,993,529</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 26.43%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">ANTISENSE MODULATION OF SUPEROXIDE DISMUTASE 1, SOLUBLE EXPRESSION</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 12.82%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2021</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 24.72%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Pharmaceutical compositions that include antisense compounds specifically hybridizable within nucleotide region of SOD-1 targeted by tofersen</div></td>
  </tr>
  <tr>
    <td style="width: 16.86%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Europe</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 12.5%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2270024</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 26.43%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">ANTISENSE MODULATION OF SUPEROXIDE DISMUTASE 1, SOLUBLE EXPRESSION</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 12.82%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2022</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 24.72%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Antisense compound specifically hybridizable within nucleotide region of SOD-1 targeted by tofersen</div></td>
  </tr>
  <tr>
    <td style="width: 16.86%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">United States</div><div>&#160;</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 12.5%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10,385,341</div><div>&#160;</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 26.43%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">COMPOSITIONS FOR MODULATING SOD-1 EXPRESSION</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 12.82%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2035</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 24.72%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Composition of tofersen</div></td>
  </tr>
  <tr>
    <td style="width: 16.86%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">United States</div><div>&#160;</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 12.5%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10,669,546</div><div>&#160;</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 26.43%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">COMPOSITIONS FOR MODULATING SOD-1 EXPRESSION</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 12.82%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2035</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 24.72%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Methods of treating a SOD-1 associated neurodegenerative disorder by administering tofersen</div></td>
  </tr>
  <tr>
    <td style="width: 16.86%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Europe</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 12.5%; vertical-align: top; background-color: #CCEEFF;"><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: #CCEEFF;">&#160;</td>
    <td style="width: 26.43%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">COMPOSITIONS FOR MODULATING SOD-1 EXPRESSION</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 12.82%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2035</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 24.72%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Composition of tofersen</div></td>
  </tr>
</table>
<div><br /></div>
<div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
<div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span>37</span></div>
</div>
<div style="page-break-after:always;"><hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>
<div></div>
</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 is 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 cellpadding="0" cellspacing="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" id="z4109c93a96a745819d31e135c18290d2">
  <tr>
    <td style="width: 16.86%; vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Jurisdiction</div></td>
    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>
    <td style="width: 12.5%; 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;">Patent No.</div></td>
    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>
    <td style="width: 26.42%; vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Title</div></td>
    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>
    <td style="width: 12.82%; vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Expiration</div></td>
    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>
    <td style="width: 24.74%; vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Description of Claims</div></td>
  </tr>
  <tr>
    <td style="width: 16.86%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">United States</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 12.5%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">9,574,193</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 26.42%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">METHODS AND COMPOSITIONS FOR MODULATING APOLIPOPROTEIN (A) EXPRESSION</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 12.82%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2033</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 24.74%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Methods of lowering Apo(a) and/or Lp(a) levels with an oligonucleotide complementary within the nucleotide region of Apo(a) targeted by p</span>elacarsen</div></td>
  </tr>
  <tr>
    <td style="width: 16.86%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">United States</div><div>&#160;</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 12.5%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10,478,448</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 26.42%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">METHODS AND COMPOSITIONS FOR MODULATING APOLIPOPROTEIN (A) EXPRESSION</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 12.82%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2033</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 24.74%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Methods of treating hyperlipidemia with an oligonucleotide complementary within the nucleotide region of Apo(a) targeted by p</span>elacarsen</div></td>
  </tr>
  <tr>
    <td style="width: 16.86%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">United States</div><div>&#160;</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 12.5%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">9,884,072</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 26.42%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">METHODS AND COMPOSITIONS FOR MODULATING APOLIPOPROTEIN (A) EXPRESSION</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 12.82%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2033</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 24.74%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Oligonucleotides complementary within the nucleotide region of Apo(a) targeted by pelacarsen</div></td>
  </tr>
  <tr>
    <td style="width: 16.86%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Europe</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 12.5%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2855500</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 26.42%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">METHODS AND COMPOSITIONS FOR MODULATING APOLIPOPROTEIN (A) EXPRESSION</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 12.82%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2033</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 24.74%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Oligonucleotides complementary within the nucleotide region of Apo(a) targeted by pelacarsen for decreasing Apo(a) expression</div></td>
  </tr>
  <tr>
    <td style="width: 16.86%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">United States</div><div>&#160;</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 12.5%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">9,181,550</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 26.42%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">COMPOSITIONS AND METHODS FOR MODULATING APOLIPOPROTEIN (a) EXPRESSION</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 12.82%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2034</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 24.74%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Composition of p</span>elacarsen</div></td>
  </tr>
  <tr>
    <td style="width: 16.86%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Europe</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 12.5%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2992009</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 26.42%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">COMPOSITIONS AND METHODS FOR MODULATING APOLIPOPROTEIN (a) EXPRESSION</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 12.82%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2034</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 24.74%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Composition of pelacarsen</div></td>
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<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">IONIS-TTR-L<sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> and Transthyretin</span></div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We believe IONIS-TTR-L</span><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 2034. Additional patent applications to protect IONIS-TTR-L</span><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-TTR-L<sub>Rx</sub><sub>&#xA0;</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 cellpadding="0" cellspacing="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" id="zf14df0ee46124667bd1e5d7303ba52ad">
  <tr>
    <td style="width: 14.22%; 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;">Jurisdiction</div></td>
    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>
    <td style="width: 12.5%; 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;">Patent No.</div></td>
    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>
    <td style="width: 27.44%; vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Title</div></td>
    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>
    <td style="width: 12.82%; vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Expiration</div></td>
    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>
    <td style="width: 26.35%; vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Description of Claims</div></td>
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    <td style="width: 14.22%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">United States</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 12.5%; vertical-align: top; background-color: #CCEEFF;"><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: 27.44%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">COMPOSITIONS AND METHODS FOR MODULATING TTR EXPRESSION</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 12.82%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2034</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 26.35%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Composition of IONIS-TTR-L<sub>Rx</sub></div></td>
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    <td style="width: 14.22%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Europe</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 12.5%; vertical-align: top; background-color: #FFFFFF;"><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: 27.44%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">COMPOSITIONS AND METHODS FOR MODULATING TTR EXPRESSION</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 12.82%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2034</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 26.35%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Composition of IONIS-TTR-L<sub>Rx</sub></div></td>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">IONIS-APOCIII-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 believe IONIS-APOCIII-L<sub>Rx</sub> is protected from generic competition in the U.S. and Europe until at least 2034. Additional patent applications to protect IONIS-APOCIII-L<sub>Rx</sub> in other foreign jurisdictions are being pursued. The table below lists some key issued patents protecting IONIS-APOCIII-L<sub>Rx</sub> in the U.S. and Europe.</div>
<div><br /></div>
<table cellpadding="0" cellspacing="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" id="zc8c41d8b97e24b0ca69b196c40439c66">
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    <td style="width: 14.22%; 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;">Jurisdiction</div></td>
    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>
    <td style="width: 11.11%; vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Patent No.</div></td>
    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>
    <td style="width: 27.99%; vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Title</div></td>
    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>
    <td style="width: 12.82%; vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Expiration</div></td>
    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>
    <td style="width: 27.19%; vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Description of Claims</div></td>
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    <td style="width: 14.22%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">United States</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 11.11%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">9,163,239</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 27.99%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">COMPOSITIONS AND METHODS FOR MODULATING APOLIPOPROTEIN C-III EXPRESSION</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 12.82%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2034</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 27.19%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Composition of IONIS-APOCIII-L<sub>Rx</sub></div></td>
  </tr>
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    <td style="width: 14.22%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Europe</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 11.11%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2991656</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 27.99%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">COMPOSITIONS AND METHODS FOR MODULATING APOLIPOPROTEIN C-III EXPRESSION</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 12.82%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2034</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 27.19%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Composition of IONIS-APOCIII-L<sub>Rx</sub></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 seek patent protection in significant markets and/or countries for each medicine in development. We also seek to maximize patent term. In some cases, the patent term can be extended to recapture a portion of the term lost during FDA regulatory review. The patent exclusivity period for a medicine will prevent generic medicines from entering the market. Patent exclusivity depends on a number of factors including initial patent term and available patent term extensions based upon delays caused by the regulatory approval process.</div>
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<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><span style="text-decoration: underline;">Manufacturing Patents</span></div>
<div style="text-align: justify; text-indent: 36pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> </span><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We also own patents claiming methods of manufacturing and purifying oligonucleotides. These patents claim methods for improving oligonucleotide drug manufacturing, including processes for large-scale oligonucleotide synthesis and purification. These methods allow us to manufacture oligonucleotides at lower cost by, for example, eliminating expensive manufacturing steps.</div>
<div style="text-align: justify; text-indent: 36pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> </span><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We also rely on trade secrets, proprietary know-how and continuing technological innovation to develop and maintain a competitive position in antisense therapeutics.</div>
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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Government Regulation</div>
<div style="text-align: justify;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> </span><br /></div>
<div style="text-align: justify; text-indent: 35pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Regulation by government authorities in the U.S. and other countries is a significant component in the development, manufacture and commercialization of pharmaceutical products and services. In addition to regulations enforced by the FDA and relevant foreign regulatory authorities, we are also subject to regulation under the Occupational Safety and Health Act, the Environmental Protection Act, the Toxic Substances Control Act, the Resource Conservation and Recovery Act and other present and potential future federal, state and local regulations.</div>
<div style="text-align: justify; text-indent: 35pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> </span><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Extensive regulation by the U.S. and foreign governmental authorities governs the development, manufacture and sale of our medicines. In particular, our medicines are subject to a number of approval requirements by the FDA in the U.S. under the Federal Food, Drug and Cosmetic Act, or FDCA, and other laws and by comparable agencies in those foreign countries in which we conduct business. The FDCA and other various federal, state and foreign statutes govern or influence the research, testing, manufacture, safety, labeling, storage, recordkeeping, approval, promotion, marketing, distribution, post-approval monitoring and reporting, sampling, quality, and import and export of our medicines. State, local, and other authorities also regulate pharmaceutical manufacturing facilities and procedures.</div>
<div style="text-align: justify; text-indent: 36pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> </span><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our manufacturing facility and our CMOs are subject to periodic inspection by the FDA and other foreign equivalents to ensure that they are operating in compliance with cGMP requirements. In addition, marketing authorization for each new medicine may require a rigorous manufacturing pre-approval inspection by regulatory authorities. Post approval, there are strict regulations regarding changes to the manufacturing process, and, depending on the significance of the change, changes may require prior FDA approval. FDA regulations also require investigation and correction of any deviations from cGMP and impose reporting and documentation requirements upon us and any third-party manufacturers that we may decide to use.</div>
<div style="text-align: justify; text-indent: 36pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> </span><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The FDA must approve any new medicine before a manufacturer can market it in the U.S. In order to obtain approval, we and our partners must complete clinical studies and prepare and submit an NDA to the FDA. If the FDA approves a medicine, it will issue an approval letter authorizing commercial marketing of the medicine and may require a risk evaluation and mitigation strategy, or REMS, to help ensure the benefits of the medicine outweigh the potential risks. For example, TEGSEDI has a REMS program. The requirements for REMS can materially affect the potential market and profitability of our medicines. In foreign jurisdictions, the drug approval process is similarly demanding.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">For any approved medicine, domestic and foreign sales of the medicine depend, in part, on the availability and amount of coverage and adequate reimbursement by third-party payors, including governments and private health plans. The process for determining whether a payor will provide coverage for a product may be separate from the process for setting the reimbursement rate that the payor will pay for the product, or procedures which utilize such product. Private health plans may seek to manage cost and use of our medicines by implementing coverage and reimbursement limitations. For example, third-party payors may limit coverage to specific products on an approved list, or formulary, which might not include all of U.S. FDA-approved products for a particular indication. In certain jurisdictions, governments may also regulate or influence coverage, reimbursement and/or pricing of our medicines to control cost or affect use. Within the EU a variety of payors pay for medicines, with governments being the primary source of payment. Negotiating pricing with governmental authorities can delay commercialization. Such pricing and reimbursement factors could impact our ability and that of our commercial partners to successfully commercialize approved medicines. Further, it is possible that additional governmental action is taken in response to the COVID-19 pandemic.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In the U.S. and foreign jurisdictions, the legislative landscape continues to evolve. There have been a number of legislative and regulatory changes to the healthcare system that could affect our future results of operations. In particular, there have been and continue to be a number of initiatives at the U.S. federal and state levels and by foreign governments that seek to reduce healthcare costs. 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. Further, it is possible that additional governmental action is taken in response 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 addition, the distribution of prescription pharmaceutical products is subject to the Prescription Drug Marketing Act, or PDMA, and its implementing regulations, as well as the Drug Supply Chain Security Act, or DSCA, which regulate the distribution and tracing of prescription drugs and prescription drug samples at the federal level, and set minimum standards for the regulation of drug distributors by the states. The PDMA, its implementing regulations and state laws limit the distribution of prescription pharmaceutical product samples, and the DSCA imposes requirements to ensure accountability in distribution and to identify and remove counterfeit and other illegitimate products from the market.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Other healthcare laws that may affect our ability to operate include, for example, the following:</div>
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    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The federal Health Insurance Portability and Accountability Act of 1996, or HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act, which governs the conduct of certain electronic healthcare transactions and protects the security and privacy of protected health information;</div></td>
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    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Foreign and state laws governing the privacy and security of health information, such as the General Data Protection Regulation, or GDPR, in the EU; and the California Consumer Privacy Act, or CCPA, in California, some of which are more stringent than HIPAA and many of which differ from each other in significant ways and may not have the same effect; and</div></td>
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    <td style="width: 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 U.S. Department of Health and Human Services information related to payments and other transfers of value to physicians, other healthcare providers and teaching hospitals, and ownership and investment interests held by physicians and their immediate family members.</div></td>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">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 U.S. Department of Health and Human Services, the U.S. Department of Justice, and similar foreign, state and local government authorities, regulate sales, promotion and other activities following drug approval. As described above, the FDA regulates all advertising and promotion activities for drugs under its jurisdiction both prior to and after approval. Only those claims relating to safety and efficacy that the FDA has approved may be used in labeling. Physicians may prescribe legally available drugs for uses that are not described in the drug&#8217;s labeling and that differ from those we tested and the FDA approved. Such off-label uses are common across medical specialties and often reflect a physician&#8217;s belief that the off-label use is the best treatment for the patients. The FDA does not regulate the behavior of physicians in their choice of treatments, but FDA regulations do impose stringent restrictions on manufacturers&#8217; communications regarding off-label uses. If we do not comply with applicable FDA requirements, we may face adverse publicity, enforcement action by the FDA, corrective advertising, consent decrees and the full range of civil and criminal penalties available to the FDA. Promotion of off-label uses of drugs can also implicate the false claims laws described below.</div>
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<div style="text-align: justify; text-indent: 40.8pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In the U.S. sales, marketing and scientific/educational programs must also comply with various federal and state laws pertaining to healthcare &#8220;fraud and abuse,&#8221; including anti-kickback laws and false claims laws. Anti-kickback laws make it illegal for a prescription drug manufacturer to solicit, offer, receive, or pay any remuneration in exchange for, or to induce, the referral of business, including the purchase or prescription of a particular drug. Due to the breadth of the statutory provisions, limited statutory exceptions and regulatory safe harbors, and the absence of guidance in the form of regulations and very few court decisions addressing industry practices, it is possible that our practices might be challenged under anti-kickback or similar laws. Moreover, recent healthcare reform legislation has strengthened these laws. For example, the PPACA 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, PPACA clarifies that the government may assert that a claim that includes items or services resulting from a violation of the federal anti-kickback statute constitutes a false or fraudulent claim for purposes of the false claims statutes. False claims laws prohibit anyone from knowingly and willingly presenting, or causing to be presented for payment, to third-party payers (including Medicare and Medicaid) claims for reimbursed drugs or services that are false or fraudulent, claims for items or services not provided as claimed, or claims for medically unnecessary items or services. Our activities relating to the sale and marketing of our drugs may be subject to scrutiny under these laws. Violations of fraud and abuse laws may be punishable by criminal and civil sanctions, including fines and civil monetary penalties, the possibility of exclusion from federal healthcare programs (including Medicare and Medicaid) and corporate integrity agreements, which impose, among other things, rigorous operational and monitoring requirements on companies. Similar sanctions and penalties also can be imposed upon executive officers and employees, including criminal sanctions against executive officers under the so-called &#8220;responsible corporate officer&#8221; doctrine, even in situations where the executive officer did not intend to violate the law and was unaware of any wrongdoing.</div>
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<div style="text-align: justify; text-indent: 40.8pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Given the significant penalties and fines that can be imposed on companies and individuals if convicted, allegations of such violations often result in settlements even if the company or individual being investigated admits no wrongdoing. Settlements often include significant civil sanctions, including fines and civil monetary penalties, and corporate integrity agreements. If the government were to allege or convict us or our executive officers of violating these laws, our business could be harmed. In addition, private individuals can bring similar actions. Our activities could be subject to challenge for the reasons discussed above and due to the broad scope of these laws and the increasing attention being given to them by law enforcement authorities. Other healthcare laws that may affect our ability to operate include 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; analogous state laws governing the privacy and security of health information, some of which are more stringent than HIPAA and many of which differ from each other in significant ways and may not have the same effect, and the Physician Payments Sunshine Act, which requires manufacturers of drugs, devices, biologics, and medical supplies to report annually to the U.S. Department of Health and Human Services information related to payments and other transfers of value to physicians and teaching hospitals, and ownership and investment interests held by physicians and their immediate family members. Further, there are an increasing number of state laws that require manufacturers to make reports to states on pricing and marketing information. Many of these laws contain ambiguities as to what is required to comply with the laws. Given the lack of clarity in laws and their implementation, our reporting actions could be subject to the penalty provisions of the pertinent state authorities.</div>
<div 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>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The U.S. Foreign Corrupt Practices Act, or FCPA, prohibits certain individuals and entities, including us, from promising, paying, offering to pay, or authorizing the payment of anything of value to any foreign government official, directly or indirectly, to obtain or retain business or an improper advantage. If we violate the FCPA, it could result in large civil and criminal penalties as well as an adverse effect on our reputation, operations, and financial condition. We could also face collateral consequences such as debarment and the loss of export privileges.</div>
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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Competition</div>
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<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 style="text-align: justify; text-indent: 39.6pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> </span><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Some of our medicines may compete with existing therapies for market share and some of our medicines in development may compete for patients in study trials. In addition, there are a number of companies pursuing the development of oligonucleotide-based technologies and the development of pharmaceuticals utilizing these technologies. These companies include biopharmaceutical companies and large pharmaceutical companies acting either independently or together. Our medicines are differentiated from traditional small molecule medicines by their chemistry, how they move in the body, how they act in the body, delivery technology, and formulations.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our approved products and our products under development address numerous markets. The diseases our medicines target for which we have or may receive marketing authorization will determine our competition. For some of our products, an important factor may be the timing of market introduction of competitive products. Accordingly, the relative speed with which we can develop products, complete the clinical trials and marketing authorization processes and supply commercial quantities of the products 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 convenience, marketing and sales strategy and tactics, availability, price, and reimbursement.</div>
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<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 the competitive landscape for our marketed medicines and for the medicines we currently have in Phase 3 trials. We have included medicines that we believe compete or may compete directly with our medicines. We included competitors, potential competitors that are past Phase 1 development or potential competitors that plan to start a pivotal study this year. We do not b<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">elieve that any medicines meet these criteria to compete with pelacarsen.</span></div>
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<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span>41</span></div>
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<div style="text-align: justify; margin-left: 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;">We consider the following medicines as competitors and potential future competitors to SPINRAZA for the indication of SMA:</div>
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<table cellpadding="0" cellspacing="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" id="z8e05bc41f7834f18b06b71262620cad3">
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    <td style="width: 17.14%; 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: 12.67%; vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Company</div></td>
    <td style="width: 2.44%; vertical-align: bottom;">&#160;</td>
    <td style="width: 22.71%; vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Medicine Description</span><sup> (1)</sup></div></td>
    <td style="width: 2.44%; vertical-align: bottom;">&#160;</td>
    <td style="width: 21.03%; vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Phase</span><sup> (1)</sup></div></td>
    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>
    <td style="width: 18.24%; vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Route of Administration</span><sup> (1)</sup></div></td>
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    <td style="width: 17.14%; vertical-align: top; background-color: #CCEEFF;"><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: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 12.67%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Novartis</div></td>
    <td style="width: 2.44%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 22.71%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Gene therapy targeting the genetic root cause of SMA by replacing the missing or nonworking SMN1 gene</div></td>
    <td style="width: 2.44%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 21.03%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Approved for Type 1 infants younger than two years old</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 18.24%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Intravenous infusion</div></td>
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    <td style="width: 17.14%; vertical-align: top; background-color: #FFFFFF;"><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: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 12.67%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">PTC/ Roche/ SMA Foundation</div></td>
    <td style="width: 2.44%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 22.71%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">A small molecule medicine that modulates splicing of the SMN2 gene</div></td>
    <td style="width: 2.44%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 21.03%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Approved in the U.S.</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 18.24%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Oral</div></td>
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    <td style="width: 36pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 8pt;">(1)</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Taken from public documents including respective company press releases, company presentations, and scientific presentations.</div></td>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In May 2019, onasemnogene abeparvovec was approved for the treatment of pediatric patients less than two years of age with SMA including those who are presymptomatic at diagnosis.</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 2020, the FDA approved risdiplam for the treatment of SMA in adults and children two months of age and older.</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;">TEGSEDI and IONIS-TTR-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 consider the following medicines as competitors and potential future competitors to TEGSEDI and IONIS-TTR-L<sub>Rx</sub> for the indication of hATTR amyloidosis and/or ATTR cardiomyopathy:</div>
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<table cellpadding="0" cellspacing="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" id="zbf116b487aca4d629f8bfb5643852eb2">
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    <td style="width: 15.83%; vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Medicine</div></td>
    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>
    <td style="width: 12.5%; 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;">Company</div></td>
    <td style="width: 2.5%; vertical-align: bottom;">&#160;</td>
    <td style="width: 23.33%; vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Medicine Description</span><sup> (1)</sup></div></td>
    <td style="width: 2.5%; vertical-align: bottom;">&#160;</td>
    <td style="width: 21.65%; vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Phase</span><sup> (1)</sup></div></td>
    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>
    <td style="width: 18.35%; vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Route of Administration</span><sup> (1)</sup></div></td>
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    <td style="width: 15.83%; vertical-align: top; background-color: #CCEEFF;"><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: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 12.5%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Alnylam</div></td>
    <td style="width: 2.5%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 23.33%; vertical-align: top; background-color: #CCEEFF;"><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: 2.5%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 21.65%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Approved hATTR/</div><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: 18.35%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Intravenous infusion</div></td>
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    <td style="width: 15.83%; vertical-align: top; background-color: #FFFFFF;"><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: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 12.5%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Pfizer</div></td>
    <td style="width: 2.5%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 23.33%; vertical-align: top; background-color: #FFFFFF;"><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: 2.5%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 21.65%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Approved in U.S., EU, Japan and select other markets for hATTR-PN and/or ATTR-CM; indications vary by region</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 18.35%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Oral</div></td>
  </tr>
  <tr>
    <td style="width: 15.83%; vertical-align: top; background-color: #CCEEFF;"><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: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 12.5%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Alnylam</div></td>
    <td style="width: 2.5%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 23.33%; vertical-align: top; background-color: #CCEEFF;"><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: 2.5%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 21.65%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 18.35%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Subcutaneous Injection</div></td>
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    <td style="width: 15.83%; vertical-align: top; background-color: #FFFFFF;"><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: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 12.5%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Bridgebio</div></td>
    <td style="width: 2.5%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 23.33%; vertical-align: top; background-color: #FFFFFF;"><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: 2.5%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 21.65%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 18.35%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Oral</div></td>
  </tr>
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    <td style="width: 36pt; vertical-align: top; align: right; 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: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our main competition for TEGSEDI is patisiran, marketed by Alnylam Pharmaceuticals. Although patisiran requires intravenous administration by a healthcare provider every three weeks and pre-treatment with steroids, it does not have a boxed warning or REMS as TEGSEDI does.</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 Alnylam&#8217;s </span>patisiran<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> and vutrisiran could compete directly against IONIS-TTR-L</span><sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, given their transthyretin-silencing profile. </span>While their approved indications vary by market, the transthyretin stabilizers, tafamidis/ tafamidis meglumine, marketed by Pfizer, are currently the only approved products for the treatment of ATTR-CM.</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;">WAYLIVRA and IONIS-APOCIII-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 believe that the following medicines could compete with WAYLIVRA and IONIS-APOCIII-L<sub>Rx</sub> in FCS:</div>
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<table cellpadding="0" cellspacing="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" id="z3667b92e64c44b8b9a4b95f1e26f288e">
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    <td style="width: 15.62%; 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: 18.25%; vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Company</div></td>
    <td style="width: 2.24%; vertical-align: bottom;">&#160;</td>
    <td style="width: 29.68%; vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Medicine Description</span><sup> (1)</sup></div></td>
    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>
    <td style="width: 10.97%; vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Phase</span><sup> (1)</sup></div></td>
    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>
    <td style="width: 18.24%; vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Route of Administration</span><sup> (1)</sup></div></td>
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    <td style="width: 15.62%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Lomitapide</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 18.25%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Amryt Pharma</div></td>
    <td style="width: 2.24%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 29.68%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Microsomal triglyceride transfer protein (MTP) inhibitor</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 10.97%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 18.24%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Oral</div></td>
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    <td style="width: 15.62%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">ARO-APOC3</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 18.25%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Arrowhead Pharmaceuticals</div></td>
    <td style="width: 2.24%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 29.68%; vertical-align: top; background-color: #FFFFFF;"><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: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 10.97%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1/2</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 18.24%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Subcutaneous Injections</div></td>
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    <td style="width: 15.62%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Gemcabene</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 18.25%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">NeuroBo Pharmaceuticals</div></td>
    <td style="width: 2.24%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 29.68%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Dicarboxylic acid with antihyperlipidemic activity</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 10.97%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 18.24%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Oral</div></td>
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    <td style="width: 36pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 8pt;">(1)</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Taken from public documents including respective company press releases, company presentations, and scientific presentations.</div></td>
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<div style="text-align: left; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Tominersen</div>
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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 following medicines could compete with tominersen in Huntington&#8217;s Disease:</div>
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<table cellpadding="0" cellspacing="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" id="za3cc741ab5cd4af28f92ed53b57073b2">
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    <td style="width: 15.83%; vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Medicine</div></td>
    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>
    <td style="width: 12.5%; 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;">Company</div></td>
    <td style="width: 2.5%; vertical-align: bottom;">&#160;</td>
    <td style="width: 33.33%; vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Medicine Description</span><sup> (1)</sup></div></td>
    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>
    <td style="width: 12.5%; vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Phase</span><sup> (1)</sup></div></td>
    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>
    <td style="width: 18.33%; vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Route of Administration</span><sup> (1)</sup></div></td>
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    <td style="width: 15.83%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">WVE-120101/ WVE-120102</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 12.5%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Wave Life Sciences</div></td>
    <td style="width: 2.5%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 33.33%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Antisense medicines targeting mHTT SNP-1 and SNP-2</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 12.5%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1b/2a</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 18.33%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Intrathecal</div><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Infusion</div></td>
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    <td style="width: 15.83%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Selisistat</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 12.5%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">AOP Orphan</div></td>
    <td style="width: 2.5%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 33.33%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">An orally active, selective SIRT1 inhibitor</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 12.5%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 18.33%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Oral</div></td>
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    <td style="width: 15.83%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">VX15</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 12.5%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Vaccinex</div></td>
    <td style="width: 2.5%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 33.33%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">A monoclonal antibody that blocks the activity of SEMA4D</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 12.5%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 18.33%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Intravenous</div><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Infusion</div></td>
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    <td style="width: 15.83%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">AMT-130</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 12.5%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">UniQure</div></td>
    <td style="width: 2.5%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 33.33%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">HTT-silencing micro-RNA gene therapy</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 12.5%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1/2</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 18.33%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">MRI-guided stereotaxic infusion</div></td>
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<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="z999eb2c4b7364f048b32763a0a9e6977">
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    <td style="width: 36pt; vertical-align: top; align: right; 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: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We believe that Wave Life Sciences&#8217; WVE-120101 and WVE-120102, being developed for Huntington&#8217;s Disease, could compete directly against tominersen. These medicines are antisense medicines administered intrathecally, targeting mHTT SNP-1 and SNP-2, respectively. Wave Life Sciences is currently conducting two simultaneous Phase 1b/2a clinical trials, enrolling adults with early manifest Huntington&#8217;s disease who carry a single nucleotide polymorphism, or SNP, at the SNP1 and SNP2 location.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">UniQure has been developing AMT-130, a gene therapy for Huntington&#8217;s Disease that consists of an AA5 vector carrying an artificial micro-RNA to target mHTT gene.</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;">Tofersen</div>
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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 following medicines could potentially compete with tofersen:</div>
<div><br /></div>
<table cellpadding="0" cellspacing="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" id="z902ad37699d94aa480c92c4095e43e0b">
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    <td style="width: 15.83%; vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Medicine</div></td>
    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>
    <td style="width: 12.97%; vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Company</div></td>
    <td style="width: 2.47%; vertical-align: bottom;">&#160;</td>
    <td style="width: 33.1%; vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Medicine Description</span><sup> (1)</sup></div></td>
    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>
    <td style="width: 12.39%; vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Phase</span><sup> (1)</sup></div></td>
    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>
    <td style="width: 18.24%; vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Route of Administration</span><sup> (1)</sup></div></td>
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    <td style="width: 15.83%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Arimoclomol</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 12.97%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Orphazyme</div></td>
    <td style="width: 2.47%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 33.1%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Provides cellular protection from abnormal proteins by activating molecular &#8220;chaperone&#8221; proteins that can repair or degrade the damaged proteins</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 12.39%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 18.24%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Oral</div></td>
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    <td style="width: 15.83%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Ultomiris</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 12.97%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Alexion</div></td>
    <td style="width: 2.47%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 33.1%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Anti-C5 monoclonal antibody</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 12.39%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 18.24%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Intravenous</div><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Infusion</div></td>
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    <td style="width: 15.83%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Masitinib</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 12.97%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">AB Science</div></td>
    <td style="width: 2.47%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 33.1%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Selective tyrosine kinase inhibitor</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 12.39%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 18.24%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Oral</div></td>
  </tr>
  <tr>
    <td style="width: 15.83%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Trehalose</div><div>&#160;</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 12.97%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Seelos</div></td>
    <td style="width: 2.47%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 33.1%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">A disaccharide that stabilizes proteins and activates autophagy to clear materials from damaged cells</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 12.39%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2/3</div></td>
    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 18.24%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Intravenous</div><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Infusion</div></td>
  </tr>
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<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="z18904461704946df947c4ee1a6e7871f">
  <tr>
    <td style="width: 36pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 8pt;">(1)</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Taken from public documents including respective company press releases, company presentations, and scientific presentations.</div></td>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Employees &amp; Human Capital</div>
<div style="text-align: justify; text-indent: 36pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> </span><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">As of February 18, 2021, we employed 757 people, the vast majority of whom reside in the United States. 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 2020 was 11.5 percent, excluding reductions related to the Akcea Acquisition, while the turnover for life sciences/ medical device companies over this period was 21 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;">Employees are rewarded individually on the basis of their responsibilities and accomplishments. We offer fair, competitive compensation and benefits to our employees. In addition to salary and bonus programs, we also offer:</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="z4de19afc7a81443fa855d152a31bdc6e">
  <tr>
    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; 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>
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<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="z0865313c679e413f93b774260cf337c4">
  <tr>
    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; 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>
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  <tr>
    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; 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 Employee Stock Purchase Plan, or ESPP</div></td>
  </tr>
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<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="z98440193a3004dd595fcd1ce047010e7">
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    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; 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>
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<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="z64e949097dd44bc5a52ca135f7fde9d9">
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    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; 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>
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    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; 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>
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  <tr>
    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; 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>
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<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="z5269fc6b56614178b2273eafd68c913a">
  <tr>
    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; 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>
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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;">We recognize achievements with salary increases, stock awards, promotions, and bonus opportunities.</div>
<div><br /></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Pay Equity</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We are committed to paying our employees fairly, regardless of their gender, race, or other personal characteristics. To ensure we are achieving our commitment, we benchmark and evaluate pay based on market data and consider factors such as an employee&#8217;s role and experience, an employee&#8217;s performance and internal equity. We also regularly review our compensation practices, both 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: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In 2018, we engaged an independent third-party expert to perform a pay equity analysis which reviewed pay equity by gender and race. We plan to continue to engage a third-party expert to review pay equity every two to three years, as we determine necessary.</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 in order 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.</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. 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 yes 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 which houses important information on career growth and planning. By supporting our employees, we know that each professional development milestone enables our continued success.</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;">COVID-19 Response</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">As a company focused on improving the health of people around the world, our priority during the COVID-19 pandemic is the safety of our employees, their families, the healthcare workers who work with us and the patients who rely on our medicines. In order to keep employees safe, the majority of the Ionis workforce began working remotely in March 2020 and is doing so efficiently. We have also provided flexible work arrangements to employees as necessary.</div>
<div><br /></div>
<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Information about our Executive Officers</div>
<div style="text-align: justify; text-indent: 36pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> </span><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following sets forth certain information regarding our executive officers as of February 18, 2021:</div>
<div style="text-align: left;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> </span><br /></div>
<table cellpadding="0" cellspacing="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" id="z96a74967144742b58ea2e392ef7f1956">
  <tr>
    <td style="width: 25.83%; vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Name</div></td>
    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>
    <td style="width: 8.33%; vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Age</div></td>
    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>
    <td style="width: 62.5%; vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Position</div></td>
  </tr>
  <tr>
    <td style="width: 25.83%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Stanley T. Crooke, M.D., 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;">75</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 Chairman of the Board of Directors</div></td>
  </tr>
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    <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;">Brett P. Monia, 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;">59</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;">Chief Executive Officer</div></td>
  </tr>
  <tr>
    <td style="width: 25.83%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">C. Frank Bennett, Ph.D.</div></td>
    <td style="width: 1.67%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 8.33%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">64</div></td>
    <td style="width: 1.67%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 62.5%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Executive Vice President, Chief Scientific Officer</div></td>
  </tr>
  <tr>
    <td style="width: 25.83%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Onaiza Cadoret-Manier</div></td>
    <td style="width: 1.67%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 8.33%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">56</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 Corporate Development and Commercial Officer</div></td>
  </tr>
  <tr>
    <td style="width: 25.83%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Richard S. Geary, Ph.D.</div></td>
    <td style="width: 1.67%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 8.33%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">63</div></td>
    <td style="width: 1.67%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 62.5%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Executive Vice President, Chief Development Officer</div></td>
  </tr>
  <tr>
    <td style="width: 25.83%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Elizabeth L. Hougen</div></td>
    <td style="width: 1.67%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 8.33%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">59</div></td>
    <td style="width: 1.67%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 62.5%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Executive Vice President, Finance and Chief Financial Officer</div></td>
  </tr>
  <tr>
    <td style="width: 25.83%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Patrick R. O&#8217;Neil, Esq.</div></td>
    <td style="width: 1.67%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 8.33%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">47</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, Legal &amp; General Counsel, Chief Compliance Officer and Corporate Secretary</div></td>
  </tr>
  <tr>
    <td style="width: 25.83%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Eugene Schneider, M.D.</div></td>
    <td style="width: 1.67%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 8.33%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">48</div></td>
    <td style="width: 1.67%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 62.5%; vertical-align: top; background-color: #FFFFFF;"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Executive Vice President, Chief Clinical Development Officer</div></td>
  </tr>
  <tr>
    <td style="width: 25.83%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Eric E. Swayze, Ph.D.</div></td>
    <td style="width: 1.67%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 8.33%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">55</div></td>
    <td style="width: 1.67%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 62.5%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Executive Vice President, Research</div></td>
  </tr>
</table>
<div><br /></div>
<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">STANLEY T. CROOKE, M.D., Ph.D.</div>
<div style="text-align: justify;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> </span><br /></div>
<div style="text-align: justify; text-indent: -18pt; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Executive Chairman of Ionis&#8217; Board of Directors</div>
<div style="text-align: justify; text-indent: -18pt; margin-left: 54pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> </span><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Dr. Crooke is a founder of Ionis and became Executive Chairman of our board of directors in January 2020. Dr. Crooke served as Chief Executive Officer and a Director from January 1989 to January 2020. He was elected Chairman of the Board in February 1991. Prior to founding Ionis, from 1980 until January 1989, Dr. Crooke was employed by SmithKline Beckman Corporation, a pharmaceutical company, where his titles included President of Research and Development of SmithKline and French Laboratories.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In June 2021, Dr. Crooke will retire from Ionis and our Board of Directors. After his retirement, Dr. Crooke will continue to serve as a scientific advisor to Ionis.</div>
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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">BRETT P. MONIA, Ph.D.</div>
<div style="text-align: justify;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> </span><br /></div>
<div style="text-align: justify; text-indent: -18pt; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Chief Executive Officer</div>
<div style="text-align: justify; text-indent: -18pt; margin-left: 54pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> </span><br /></div>
<div style="text-align: justify; text-indent: 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>
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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">C. FRANK BENNETT, Ph.D.</div>
<div style="text-align: justify;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> </span><br /></div>
<div style="text-align: justify; text-indent: -18pt; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Executive Vice President, Chief Scientific Officer</div>
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<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 an external member of the Scientific Advisory Board of Experimental Therapeutics Center in Singapore and the Hereditary Disease Foundation.</div>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">ONAIZA CADORET-MANIER</div>
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<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Executive Vice President, Chief Corporate Development and Commercial Officer</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;">Ms. Cadoret-Manier has served as Ionis&#8217; Executive Vice President, </span>Chief Corporate Development and Commercial Officer<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">&#xA0;</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">since April 2020. Ms. Cadoret-Manier joined Ionis as Chief Corporate Development and Commercial Officer in January 2020. Prior to joining Ionis, from 2018 to 2019 Ms. Cadoret-Manier was the chief commercial officer for Grail Biosciences, an early detection genomics company. Prior to Grail, Ms. Cadoret-Manier was vice president of the Respiratory Franchise at Genentech where she worked from 2011 to 2018. Ms. Cadoret-Manier also has held multiple senior management positions overseeing corporate strategy, alliances, and marketing and sales for numerous disease areas for Genentech, Pfizer and Amylin Pharmaceuticals.</span></div>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">RICHARD S. GEARY, Ph.D.</div>
<div style="text-align: justify;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> </span><br /></div>
<div style="text-align: justify; text-indent: -18pt; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Executive Vice President, Chief Development Officer</div>
<div style="text-align: justify; text-indent: -18pt; margin-left: 54pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> </span><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Dr. Geary has served as Ionis&#8217; Executive Vice President, Chief Development Officer since January 2021. From April 2020 to December 2020, Dr. Geary served as our Executive Vice President, Development and from August 2008 to March 2020, was our Senior Vice President, Development. From August 2003 to August 2008, Dr. Geary served as our Vice President, Preclinical Development. From November 1995 to August 2003, he held various positions within the Preclinical Development department. Prior to joining Ionis in 1995, Dr. Geary was Senior Research Scientist and Group Leader for the bioanalytical and preclinical pharmacokinetics group in the Applied Chemistry Department at Southwest Research Institute.</div>
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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">ELIZABETH L. HOUGEN</div>
<div style="text-align: justify;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> </span><br /></div>
<div style="text-align: justify; text-indent: -18pt; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Executive Vice President, Finance and Chief Financial Officer</div>
<div style="text-align: justify; text-indent: -18pt; margin-left: 54pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> </span><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Ms. Hougen has served as Ionis&#8217; Executive Vice President and Chief Financial Officer since April 2020. From January 2013 to March 2020, Ms. Hougen served as our Senior Vice President, Finance and Chief Financial Officer. From January 2007 to December 2012, Ms. Hougen served as our Vice President, Finance and Chief Accounting Officer and from May 2000 to January 2007, she served as our Vice President, Finance. Prior to joining Ionis in 2000, Ms. Hougen was Executive Director, Finance and Chief Financial Officer for Molecular Biosystems, Inc., a public biotechnology company.</div>
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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">PATRICK R. O&#8217;NEIL, Esq.</div>
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<div style="text-align: justify; text-indent: -18pt; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Executive Vice President, Legal, General Counsel, Chief Compliance Officer and Corporate Secretary</div>
<div style="text-align: justify; text-indent: -18pt; margin-left: 54pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> </span><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Mr. O&#8217;Neil has served as Ionis&#8217; Executive Vice President, Legal and General Counsel. Mr. O&#8217;Neil also serves as our Chief Compliance Officer and Corporate Secretary. From January 2013 to March 2020, Mr. O&#8217;Neil served as our Senior Vice President, Legal and General Counsel. From September 2010 to January 2013, Mr. O&#8217;Neil served as our Vice President, Legal and General Counsel and from January 2009 to September 2010, he served as our Vice President, Legal and Senior Transactions Counsel. From October 2001 to January 2009 he held various positions within our Legal department. Prior to joining Ionis, Mr. O&#8217;Neil was an associate at Cooley LLP.</div>
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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">EUGENE SCHNEIDER, M.D.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Executive Vice President, Chief Clinical Development Officer</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Dr. Schneider was promoted to Executive Vice President and Chief Clinical Development Officer of Ionis in January 2021. From August 2018 to December 2020, Dr. Schneider served as our Senior Vice President, Head of Clinical Development. From April 2015 to July 2018, Dr. Schneider was our Vice President, Clinical Development, Severe and Rare Diseases. Dr. Schneider joined Ionis in December 2013 as Executive Director, Clinical Development. Dr. Schneider has two decades of experience in clinical development primarily in the rare diseases space. Prior to joining Ionis, Dr. Schneider was senior medical director at both Synageva BioPharma and Biovail Technologies Ltd.</div>
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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">ERIC E. SWAYZE, Ph.D.</div>
<div style="text-align: justify;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> </span><br /></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>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Dr. Swayze has served as Ionis&#8217; Executive Vice President, Research since April 2020 and is responsible for leading preclinical antisense drug discovery and antisense technology research. In January 2020, Dr. Swayze was promoted to Senior Vice President of Research. Previously, Dr. Swayze was Vice President of Chemistry and Neuroscience Drug Discovery at Ionis, overseeing the advancement of multiple programs to clinical development. He joined Ionis in 1994 and has contributed to key technology advancements, including Ionis&#8217; Generation 2.5 chemistry and LICA technology.</div>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Item 1A. RISK FACTORS</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Investing in our securities involves a high degree of risk. You should consider carefully the following information about the risks described below, together with the other information contained in this report and in our other public filings in evaluating our business. If any of the following risks actually occur, our business could be materially harmed, and our financial condition and results of operations could be materially and adversely affected. As a result, the trading price of our securities could decline, and you might lose all or part of your investment.</div>
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<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Risks Related to the COVID-19 Pandemic</div>
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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Our business could be materially adversely affected by the effects of health epidemics. To date, we believe the impacts of the recent COVID-19 pandemic on our business are limited and manageable.</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 could be materially 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 significant disruption in the operations of third-party manufacturers and contract research organizations upon whom we rely. For example, since December 2019, a novel strain of coronavirus, SARS-CoV-2, causing a disease referred to as COVID-19, has spread worldwide. In March 2020, the World Health Organization declared the COVID-19 outbreak a pandemic, or the COVID-19 Pandemic, and the U.S. government-imposed restrictions on travel between the U.S., Europe and certain other countries. In addition, the Governor of the State of California and the Governor of the Commonwealth of Massachusetts, the states in which our and Akcea&#8217;s offices are located, respectively, each declared a state of emergency related to the spread of COVID-19 and issued executive orders that directed residents to stay at home.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In response to these public health directives and orders, we implemented work-from-home policies for most of our employees globally and generally suspended business-related travel. Out of an abundance of caution and to protect the health and welfare of our employees, we continue to maintain work-from-home policies for most of our employees. We believe the effects of these work-from-home and travel policies have thus far had a limited impact on 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;">These public health directives and orders have also impacted our and our partners&#8217; sales efforts. For example, some <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">physician and hospital policies that have been put in place </span>as a result of the COVID-19 Pandemic<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> restrict in-person access by </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">third</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> parties, which has in some cases impacted our commercialization efforts for TEGSEDI and WAYLIVRA.</span> Additionally, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Biogen has reported that as a result of the COVID-19 Pandemic, SPINRAZA sales revenues have decreased in part because</span> SPINRAZA doses have been delayed due, directly or indirectly, to the COVID-19 Pandemic, and that future SPINRAZA sales revenues may be adversely affected by continued dosing delays.<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#xA0;</span>These and similar, and perhaps more severe, disruptions in our or our partner&#8217;s commercial operations could materially impact our business, operating results and financial condition in the future.</div>
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<div style="text-align: justify; text-indent: 40.5pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Quarantines, shelter-in-place, executive and similar government orders, or the perception that such orders, shutdowns or other restrictions on the conduct of business operations could occur, could impact personnel at third-party manufacturing facilities in the U.S. and other countries, or the availability or cost of materials, which would disrupt our supply chain.</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 experienced impacts to our clinical trial operations due to the COVID-19 Pandemic; however, we believe such impacts are limited and manageable. Some examples of these impacts include:</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;">we have experienced some impact on clinical site initiation and patient enrollment due to restrictions imposed as a result of the COVID-19 Pandemic;</div></td>
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    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">o</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">For example, in March 2020, we instituted a temporary suspension of enrollment for new subjects in our Phase 3 studies of IONIS-TTR-<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">L</span><sub>Rx</sub> based on advice from our trial advisory committee; however, enrollment has resumed.</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;">some patients have not been able to meet protocol requirements, as quarantines have impeded patient movement and interrupted healthcare services;</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;">we have experienced some delays in site initiations due to principle investigators and site staff focusing on and prioritizing COVID-19 patient care; and</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;">we have experienced some delays in necessary interactions with regulators, ethics committees and other important agencies and contractors due to limitations in employee resources or forced furlough of government or contractor personnel.</div></td>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The spread of COVID-19 has caused a broad impact globally. While the potential economic impact brought by, and the duration of, the COVID-19 Pandemic may be difficult to assess or predict, it could result in significant disruption of global financial markets, reducing our ability to access capital, which could in the future negatively affect our liquidity. In addition, a recession or market correction resulting from the spread of COVID-19 could materially affect our business and has and could continue to affect the value of our securities.</div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The global COVID-19 Pandemic continues to rapidly evolve. While we have not yet experienced material adverse effects to our business as a result of the COVID-19 Pandemic, the ultimate impact of the COVID-19 Pandemic or a similar health epidemic is highly uncertain and subject to change. As such, we do not yet know the full extent of delays or impacts on our business, our clinical trials, healthcare systems or the global economy as a whole. However, these effects could have a material impact on our operations, and we will continue to monitor the COVID-19 Pandemic closely.</div>
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<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Risks Related to the Commercialization of our Medicines</div>
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<div style="text-align: left; 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 may have to invest significant resources to develop these capabilities. If we are unable to establish effective marketing, sales and distribution capabilities or enter into agreements with third parties to market, sell and distribute our medicines, we may not be able to generate revenue from our medicines.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We have limited experience as a company in the marketing, sale and distribution of pharmaceutical products and 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. Any failure to effectively manage our internal sales, marketing and distribution capabilities would adversely impact the commercialization of our medicines. We may not be able to enter into collaborations or hire consultants or external service providers to assist us in sales, marketing and distribution functions on acceptable financial terms, or at all. Even if we are able to engage third parties to market, sell and distribute our medicines, our product revenues and profitability may be lower if we rely on such third parties for these functions than if we were to perform them on our own. In addition, we likely will have little control over such third parties, and any of them may fail to devote the necessary resources and attention to market, sell and distribute our medicines effectively. If we are not successful in commercializing our medicines, either on our own or through arrangements with one or more third parties, we may not be able to generate revenue from our medicines.</div>
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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">If the market does not accept our medicines, including SPINRAZA, TEGSEDI and WAYLIVRA, and our medicines in development, we are not likely to generate substantial revenues or become consistently profitable.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Even if our medicines are authorized for marketing, including SPINRAZA, TEGSEDI and WAYLIVRA, 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. We and our partners may not successfully commercialize additional medicines.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">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, then we may not be able to sell our medicines in that market. Similarly, cost control initiatives by governments or third-party payers could decrease the price received for our medicines or increase patient coinsurance to a level that makes our medicines, including SPINRAZA, TEGSEDI and WAYLIVRA, and our medicines in development, economically unviable.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The degree of market acceptance for our medicines, including SPINRAZA, TEGSEDI and WAYLIVRA, and our medicines in development, depends upon a number of factors, including the:</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;">receipt and scope of marketing authorizations;</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;">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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<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="z082d93df4ba04150859db08db817a927">
  <tr>
    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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>
  </tr>
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<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="z3c4f904db8a642f99cb6f32ebc70adc6">
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    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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>
  </tr>
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<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="zb958aaac488d4f1f98224170bd6516d1">
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    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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>
  </tr>
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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;">Based on the profile of our medicines, physicians, patients, patient advocates, payers or the medical community in general may not accept or use any medicines that we may develop.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">For example, the product label for TEGSEDI in the U.S. has a boxed warning for thrombocytopenia and glomerulonephritis, requires periodic blood and urine monitoring, and TEGSEDI is only available through a Risk Evaluation and Mitigation Strategy, or REMS, program. </span>Our main competition in the U.S. market for TEGSEDI is patisiran, marketed by Alnylam Pharmaceuticals, Inc. Although patisiran requires intravenous administration and pre-treatment with steroids, it does not have a boxed warning or REMS. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Additionally, the product label for WAYLIVRA in the EU requires regular blood monitoring. In each case, these label requirements could negatively affect our ability to attract and retain patients for these medicines. We believe that the enhanced monitoring we have implemented to support early detection and management of these issues can help manage these safety issues so that patients can continue treatment. Since implementation of the enhanced monitoring, serious platelet events have been infrequent. While we believe we can better maintain patients on TEGSEDI and WAYLIVRA through our patient-centric commercial approach where we plan to have greater involvement with physicians and patients, if we cannot effectively maintain patients on TEGSEDI or WAYLIVRA, </span>including due to limitations or restrictions on our ability to conduct periodic blood and urine monitoring of our patients as a result of the current COVID-19 Pandemic, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">we may not be able to generate substantial revenue from TEGSEDI or WAYLIVRA sales.</span></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 SPINRAZA, TEGSEDI and WAYLIVRA, and our medicines in development, will not contribute 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. Other companies are engaged in developing antisense technology. Our competitors may succeed in developing medicines that are:</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="z52317b31c1df48ec906791874132bea6">
  <tr>
    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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>
  </tr>
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<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="z238572b04faa4618a5e3f3c98bd82d77">
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    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">reimbursed more favorably by government and other third-party payers than our medicines;</div></td>
  </tr>
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<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="ze55cf6b8376b4161a22b647e7a163522">
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    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">safer than our medicines;</div></td>
  </tr>
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<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="z833beb20c26a40d8a1ed2e7e9e5f578e">
  <tr>
    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">more effective than our medicines; or</div></td>
  </tr>
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<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="z457b504a6a834a989a11d24643a39508">
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    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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>
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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;">These competitive developments could make our medicines, including SPINRAZA, TEGSEDI and WAYLIVRA, and our medicines in development, obsolete or non-competitive.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Certain of our partners are pursuing other technologies or developing other medicines either on their own or in collaboration with others, including our competitors, to treat the same diseases our own collaborative programs target. Competition may negatively impact a partner&#8217;s focus on and commitment to our medicines and, as a result, could delay or otherwise negatively affect the commercialization of our medicines, including SPINRAZA, TEGSEDI and WAYLIVRA.</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.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">There are several pharmaceutical and biotechnology companies engaged in the development or commercialization in certain geographic markets of products against targets that are also targets of products in our development pipeline. For example:</div>
<div><br /></div>
<table 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="zd4d38d8dfbe34484bc45280b12efef78">
  <tr>
    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Onasemnogene abeparvovec and risdiplam compete with SPINRAZA;</div></td>
  </tr>
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<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="z84ba36d1f47e43cdb33ae1796929fbbb">
  <tr>
    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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 and tafamidis meglumine compete with TEGSEDI;</div></td>
  </tr>
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<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="z135ec74add92481986539aea61b38e63">
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    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Vutrisiran and AG10 could compete with TEGSEDI and IONIS-TTR-L<sub>Rx</sub>;</div></td>
  </tr>
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<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="zb8fbe873e27e4d2681dc505781a74346">
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    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">;&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">ARO-APOC3, lomitapide and gemcabene could compete with WAYLIVRA and IONIS-APOCIII-L<sub>Rx</sub>;</div></td>
  </tr>
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<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="z5ba6003b2c9e4f5b9fff49182098bc04">
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    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">WVE-120101/WVE-120102, selistat, VX15 and AMT-130 could compete with tominersen; and</div></td>
  </tr>
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<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="zd1440b2aa4604ad3b17c402fb18e513d">
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    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Arimoclomol, ultomiris, mastinib and trehalose could compete with tofersen.</div></td>
  </tr>
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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;">Specifically, SPINRAZA faces competition from onasemnogene abeparvovec, a new 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, a new oral product for the treatment of SMA that was approved in the U.S. in August 2020. Biogen has disclosed that SPINRAZA revenue has decreased due in part to lower sales volumes as a result of increased competition and that future sales of SPINRAZA may be adversely affected by the commercialization of competing products. SPINRAZA injection for intrathecal use is an antisense medicine indicated for the treatment of SMA patients of all ages approved in over 50 countries.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Additionally, companies that are developing medicines that target the same patient populations as our medicines in development may compete with us to enroll participants in the clinical trials for such medicines, which could make it more difficult for us to complete enrollment for these clinical trials.</div>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Certain of our medicines may compete with our other medicines, which could reduce our expected revenues.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Certain of our medicines inhibit the production of the same protein. For example, WAYLIVRA inhibits the production of the same protein as IONIS-APOCIII-L<sub>Rx</sub> and TEGSEDI inhibits the production of the same protein as <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">IONIS-TTR-L</span><sub>Rx</sub>. We believe the enhancements we incorporated into IONIS-APOCIII-L<sub>Rx</sub> and <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">IONIS-TTR-L</span><sub>Rx</sub> can provide greater patient convenience by allowing for significantly lower doses and less frequent administration compared to WAYLIVRA and TEGSEDI, respectively. As such, to the extent physicians and patients elect to use IONIS-APOCIII-L<sub>Rx</sub> or <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">IONIS-TTR-L</span><sub>Rx</sub> instead of WAYLIVRA or TEGSEDI, respectively, it will reduce the revenue we derive from those medicines. In addition, while vupanorsen, IONIS-APOCIII-L<sub>Rx</sub> and WAYLIVRA use different mechanisms of action, if vupanorsen and IONIS-APOCIII- L<sub>Rx</sub> can effectively lower triglyceride levels in patients, including patients with FCS, WAYLIVRA, vupanorsen and IONIS-APOCIII-L<sub>Rx</sub> may compete with each other.</div>
<div><br /></div>
<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Our medicines could be subject to regulatory limitations following approval.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Following approval of a medicine, we and our partners must comply with comprehensive government regulations regarding the manufacture, marketing and distribution of medicines. Promotional communications regarding prescription medicines must be consistent with the information in the product&#8217;s approved labeling. We or our partners may not obtain the labeling claims necessary or desirable to successfully commercialize our medicines, including SPINRAZA, TEGSEDI and WAYLIVRA, 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>
<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="z0a659307a0be44ea823bda4c8146c477">
  <tr>
    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">in the U.S., TEGSEDI&#8217;s label contains a boxed warning for thrombocytopenia and glomerulonephritis;</div></td>
  </tr>
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<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="z6ddb90b18d2d48b196adec7420980ff2">
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    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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;</div></td>
  </tr>
</table>
<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="z99fed2e494b2401cb620bb7b9bfd2454">
  <tr>
    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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; and</div></td>
  </tr>
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<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="z78d66ec3f4b84d62b7da2463efe76938">
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    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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 expect WAYLIVRA will require periodic blood monitoring if approved in the U.S.</div></td>
  </tr>
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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;">Prescription medicines may be promoted only for the approved indications in accordance with the approved label. The FDA and other agencies actively enforce the laws and regulations prohibiting the promotion of off-label uses, and a company that is found to have improperly promoted off-label may be subject to significant 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, 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 authority may withdraw marketing authorization or may condition continued marketing on commitments from us or our partners that may be expensive and time consuming to fulfill.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 39.6pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">If we or others identify side effects after any of our medicines are on the market, or if manufacturing problems occur subsequent to regulatory approval, or if we, our manufacturers or our partners fail to comply with regulatory requirements, we or our partners may, among other things, lose regulatory approval and be forced to withdraw products from the market, need to conduct additional clinical studies, incur restrictions on the marketing, distribution or manufacturing of the product, and/or change the labeling of our medicines, including <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">SPINRAZA, TEGSEDI and WAYLIVRA.</span></div>
<div><br /></div>
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">We depend on our collaboration with Biogen for the development and commercialization of SPINRAZA.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We have entered into a collaborative arrangement with Biogen to develop and commercialize SPINRAZA. We entered into this collaboration primarily to:</div>
<div><br /></div>
<table 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="z7762a92a52dd473fa17200ef6de2d13f">
  <tr>
    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">fund our development activities for SPINRAZA;</div></td>
  </tr>
</table>
<table 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="z82c1cbe817e84d3daa8081de8e82a10f">
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    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">seek and obtain regulatory approvals for SPINRAZA; and</div></td>
  </tr>
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<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="zb1b722db76b7426fabb1dbd0bb315577">
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    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">successfully commercialize SPINRAZA.</div></td>
  </tr>
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<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We are relying on Biogen to obtain additional regulatory approvals for SPINRAZA, manufacture and successfully commercialize SPINRAZA. In general, we cannot control the amount and timing of resources that Biogen devotes to our collaboration. If Biogen fails to further develop SPINRAZA, obtain additional regulatory approvals for SPINRAZA, manufacture or commercialize SPINRAZA, or if Biogen&#8217;s efforts are not effective, our business may be negatively affected.</div>
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<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span>49</span></div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our collaboration with Biogen may not continue for various reasons. Biogen can terminate our collaboration at any time. If Biogen stops developing or commercializing SPINRAZA, we would have to seek or spend additional funding, and SPINRAZA&#8217;s commercialization may be harmed or delayed.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our collaboration with Biogen may not result in the continued successful commercialization of SPINRAZA. If Biogen does not continue to successfully commercialize SPINRAZA, we will receive limited revenues for SPINRAZA.</div>
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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">If we cannot optimize and maintain effective marketing and sales capabilities or enter into agreements with third parties to market and sell TEGSEDI and WAYLIVRA, we may not generate significant product revenue from TEGSEDI or WAYLIVRA.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">To successfully commercialize TEGSEDI and WAYLIVRA, we must effectively manage our marketing, sales and distribution capabilities or make arrangements with third parties to perform these services. We may not be successful in doing so. To commercialize WAYLIVRA in the initial indications we are pursuing and to continue the commercialization of TEGSEDI, we will need to optimize and maintain specialty sales forces in the global regions where we currently market or expect to market TEGSEDI and WAYLIVRA, supported by case managers, reimbursement specialists, partnerships with specialty pharmacies, injection training, routine blood and urine monitoring and a medical affairs team.</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;">Even though certain members of our management team and other employees have experience commercializing medicines, as a whole we have limited experience marketing, selling and distributing medicines, and there are </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">significant risks involved in building, tailoring, optimizing and managing a commercial infrastructure. We expect the recent </span>Akcea<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> Acquisition will result in significant turnover that could impair our ability to manage Akcea&#8217;s business. If our efforts to integrate key Akcea employees into Ionis following the Akcea Acquisition are not successful, it could impair our ability to commercialize TEGSEDI and WAYLIVRA.</span></div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#160;It is expensive and time consuming for us to maintain our own sales forces and related compliance protocols to market TEGSEDI and WAYLIVRA. We may never successfully optimize or manage this capability and any failure could harm the commercial launch of WAYLIVRA or adversely affect TEGSEDI sales. Additionally, we and our partners will have to compete with other companies to recruit, hire, train, manage and retain marketing and sales personnel.</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 have incurred expenses launching,</span>&#xA0;<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">optimizing and managing the marketing and sales infrastructure for TEGSEDI in Europe, Canada and the U.S., and WAYLIVRA in Europe. If regulatory requirements or other factors cause the commercialization of TEGSEDI or WAYLIVRA to be less successful than expected in important markets, we would incur additional expenses for having invested in these capabilities prior to realizing any significant revenue from sales of TEGSEDI or WAYLIVRA. Our sales force and marketing teams may not successfully commercialize TEGSEDI or WAYLIVRA.</span></div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">To the extent we decide to rely on third parties to commercialize TEGSEDI or WAYLIVRA in a particular geographic market, we will have less control over sales efforts and may receive less revenue than if we commercialized TEGSEDI or WAYLIVRA by ourselves. We have entered into agreements with third parties to commercialize our medicines as follows:</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 December 2020, we entered into a distribution agreement with Sobi to commercialize TEGSEDI and WAYLIVRA in Europe;</div></td>
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    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In August 2018, we granted PTC the exclusive right to commercialize TEGSEDI and WAYLIVRA in Latin America and certain Caribbean countries; and</div></td>
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    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In August 2018 we entered into an agreement with Accredo Health Group, Inc., or Accredo, a subsidiary of Express Scripts, to be our specialty pharmacy partner for distribution of TEGSEDI in the U.S.</div></td>
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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">If Sobi or PTC does not successfully commercialize TEGSEDI or WAYLIVRA, including as a result of delays or disruption caused by the current COVID-19 Pandemic, we may receive limited revenue for TEGSEDI or WAYLIVRA in Europe, Latin America or certain Caribbean countries.</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 cannot effectively build and manage our distribution, medical affairs, market access, marketing and sales infrastructure, or find a suitable third party to perform such functions, the sales of TEGSEDI and WAYLIVRA may be adversely affected. Any such events may result in decreased sales and lower revenue, which could have a material adverse effect on our business, prospects, financial condition and results 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;">In addition, in response to the public health directives and orders related to the COVID-19 Pandemic, we implemented work-from-home policies for our employees globally and suspended business-related travel. We believe the effects of the government orders and our work-from-home and travel policies in response to the COVID-19 Pandemic have thus far had a limited impact on our productivity, business and commercialization efforts for TEGSEDI and WAYLIVRA, but the effects of these orders and policies may become more significant in the future.</div>
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<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span>50</span></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 additional healthcare laws.</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 additional healthcare laws, including federal and state anti-kickback laws, false claims laws, transparency laws, such as the federal Sunshine Act, and health information privacy and security laws. Efforts to ensure that our operations comply with applicable healthcare laws and regulations involve substantial costs. 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>
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<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 SPINRAZA, TEGSEDI and WAYLIVRA, and our medicines in development, our revenue will be limited.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In both domestic and foreign markets, sales of our current and future products will depend in part upon the availability of coverage and reimbursement from third-party payers. The majority of patients in the U.S. who would fit within our target patient populations for our medicines have their healthcare supported by a combination of Medicare coverage, other government health programs such as Medicaid, managed care providers, private health insurers and other organizations. Coverage decisions may depend upon clinical and economic standards that disfavor new medicines when more established or lower cost therapeutic alternatives are already available or subsequently become available. Assuming coverage is approved, the resulting reimbursement payment rates might not be enough to make our medicines affordable. Accordingly, SPINRAZA, TEGSEDI and WAYLIVRA for FCS in the EU and, if approved, WAYLIVRA in the U.S. or Canada and for additional indications, and our medicines in development, will face competition from other therapies and medicines for limited financial resources. We or our partners may need to conduct post-marketing studies to demonstrate the cost-effectiveness of any future products to satisfy third-party payers. These studies might require us to commit a significant amount of management time and financial and other resources. Third-party payers may never consider our future products as cost-effective. Adequate third-party coverage and reimbursement might not be available to enable us to maintain price levels sufficient to realize an appropriate return on investment in product development.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Third-party payers, whether foreign or domestic, or governmental or commercial, are developing increasingly sophisticated methods of controlling healthcare costs. In addition, in the U.S., no uniform policy of coverage and reimbursement for medicines exists among third-party payers. Therefore, coverage and reimbursement for medicines can differ significantly from payer to payer. For example, the Patient Protection and Affordable Care Act, as amended by the Health Care and Education Reconciliation Act of 2010, or collectively, the Affordable Care Act, 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 remain judicial and Congressional challenges to certain aspects of the Affordable Care Act, as well as efforts to repeal or replace certain aspects of the Affordable Care Act. On December 18, 2019, the U.S. Court of Appeals for the 5th Circuit upheld the District Court ruling that the individual mandate was unconstitutional and remanded the case back to the District Court to determine whether the remaining provisions of the Affordable Care Act are invalid as well. However, in March 2020, before the District Court could rule on the remaining provisions of the Affordable Care Act, the U.S. Supreme Court agreed to review the case. In November 2020, the U.S. Supreme Court heard oral arguments and is expected to rule on the case in its current session, which began in October 2020. Although the U.S. Supreme Court has not yet ruled on the constitutionality of the Affordable Care Act, on January 28, 2021, President Biden issued an executive order to initiate a special enrollment period from February 15, 2021 through May 15, 2021 for purposes of obtaining health insurance coverage through the Affordable Care Act marketplace. It is unclear how the Supreme Court ruling, other such litigation and healthcare reform measures will impact the Affordable Care Act and our business.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Further, we believe that future coverage and reimbursement will likely be subject to increased restrictions both in the U.S. and in international markets. For example, 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 and legislation designed to, among other things, reform government program reimbursement methodologies for medicines and bring more transparency to drug pricing. Such restrictions may include legislative proposals seeking to reduce drug prices (e.g., by<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> placing limits on pharmaceutical price increases and tying</span> Medicare Part B drug prices to international drug prices), increase competition (e.g., by allowing for personal importation of drugs from Canada), lower out-of-pocket drug costs for patients (e.g., by <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">capping Medicare Part D beneficiary out-of-pocket pharmacy expenses)</span> and increase patient access to lower-cost generic and biosimilar drugs. In November 2020, the U.S. Department of Health and Human Services issued a final rule modifying the anti-kickback law safe harbors for plans, pharmacies, and pharmaceutical benefit managers. At the state level, legislatures have increasingly passed legislation and implemented regulations designed to control pharmaceutical and biological product pricing, including price or patient reimbursement constraints, discounts, restrictions on certain product access and marketing cost disclosure and transparency measures, and, in some cases, designed to encourage importation from other countries and bulk purchasing. Third-party coverage and reimbursement for medicines may not be available or adequate in either the U.S. or international markets, and third-party payers, whether foreign or domestic, or governmental or commercial, may allocate their resources to address the current COVID-19 Pandemic or experience delays or disruptions in their ability to devote resources to coverage and reimbursement matters related to our products or medicines as a result of the COVID-19 Pandemic, which would negatively affect the potential commercial success of our products, our revenue and our profits.</div>
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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">If we 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>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">To successfully commercialize any of our medicines, we would need to optimize and manage large-scale commercial manufacturing capabilities either on a standalone basis or through a third-party manufacturer. We rely on third-party manufacturers to supply the drug substance and drug product for TEGSEDI and drug product for WAYLIVRA. Any delays or disruption to our own or third-party commercial manufacturing capabilities, including any interruption to our supply chain as a result of the current COVID-19 Pandemic, could limit the commercial success of our medicines.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In addition, as our drug development pipeline increases and matures, we will have a greater need for clinical trial and commercial manufacturing capacity. 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>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Also, manufacturers, including us, must adhere to the FDA&#8217;s cGMP regulations and similar regulations in foreign countries, which the applicable regulatory authorities enforce through facilities inspection programs. We, our partners and our contract manufacturers may not comply or maintain compliance with cGMP, or similar foreign regulations. Non-compliance could significantly delay or prevent receipt of marketing authorizations for our medicines, including authorizations for SPINRAZA, TEGSEDI and WAYLIVRA, and our medicines in development, or result in enforcement action after authorization that could limit the commercial success of our medicines, including SPINRAZA, TEGSEDI and WAYLIVRA, and our medicines in development.</div>
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<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Risks Related to the Development and Regulatory Approval of our Medicines</div>
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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">If we or our partners fail to obtain regulatory approval for our medicines and additional approvals for SPINRAZA, TEGSEDI and WAYLIVRA, we or our partners cannot sell them in the applicable markets.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We cannot guarantee that any of our medicines will be considered safe and effective or will be approved for commercialization. In addition, it is possible that SPINRAZA, TEGSEDI and WAYLIVRA may not be approved in additional markets or for additional indications. We and our partners must conduct time-consuming, extensive and costly clinical studies to demonstrate the safety and efficacy of each of our medicines before they can be approved or receive additional approvals for sale. We and our partners must conduct these studies in compliance with FDA regulations and with comparable regulations in other countries.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We and our partners may not obtain necessary regulatory approvals on a timely basis, if at all, for our medicines. It is possible that regulatory agencies will not approve our medicines for marketing or SPINRAZA, TEGSEDI or WAYLIVRA in additional markets or for additional indications. If the FDA or another regulatory agency believes that we or our partners have not sufficiently demonstrated the safety or efficacy of any of our medicines, including SPINRAZA, TEGSEDI and WAYLIVRA, or our medicines in development, the agency will not approve the specific medicine or will require additional studies, which can be time consuming and expensive and which will delay or harm commercialization of the medicine. For example, in August 2018 we received a complete response letter from the FDA regarding the new drug application for WAYLIVRA in which the FDA determined that the safety concerns identified with WAYLIVRA in our clinical development program outweighed the expected benefits of triglyceride lowering in patients with FCS. We also received a Non-W from Health Canada for WAYLIVRA in November 2018. We are engaged with the FDA and plan to work with Health Canada to confirm a path forward for WAYLIVRA.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The FDA or other comparable foreign regulatory authorities can delay, limit or deny approval of a medicine for many reasons, including:</div>
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    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">such authorities may disagree with the design or implementation of our clinical studies;</div></td>
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    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">we or our partners may be unable to demonstrate to the satisfaction of the FDA or other regulatory authorities that a medicine is safe and effective for any indication;</div></td>
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    <td style="width: 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>
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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;">we or our partners may be unable to demonstrate that our medicine&#8217;s clinical and other benefits outweigh its safety risks to support approval;</div></td>
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    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">such authorities may disagree with the interpretation of data from preclinical or clinical studies;</div></td>
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    <td style="width: 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 our manufacturing processes or facilities or those of third-party manufacturers who manufacture clinical and commercial supplies for our medicines, or may delay the inspection of such facilities due to restrictions related to the COVID-19 Pandemic; and</div></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;">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>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Failure to receive marketing authorization for our medicines, or failure to receive additional marketing authorizations for SPINRAZA, TEGSEDI or WAYLIVRA, or delays in these authorizations could prevent or delay commercial introduction of the medicine, and, as a result, could negatively impact our ability to generate revenue from product sales.</div>
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<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>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Drug discovery and development has 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, 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;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In the past, we have invested in clinical studies of medicines that have not met the primary clinical end points in their Phase 3 studies. Similar results could occur in clinical studies for our medicines, including the studies of tominersen, tofersen, pelacarsen, IONIS</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">-</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">TTR-L</span><sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> and </span>IONIS-APOCIII-L<sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. If any of our medicines in clinical studies, including tominersen, tofersen, pelacarsen</span><sub>,</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, IONIS</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">-</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">TTR-L</span><sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> and </span>IONIS-APOCIII-L<sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, do not show sufficient efficacy in patients with the targeted indication, it could negatively impact our development and commercialization goals for these medicines and our stock price could decline.</span></div>
<div><br /></div>
<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Even if our medicines are successful in preclinical and human clinical studies, the medicines may not be successful in late-stage clinical studies.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Successful results in preclinical or initial human clinical studies, including the Phase 2 results for some of our medicines in development, may not predict the results of subsequent clinical studies, including the studies of tominersen, tofersen, pelacarsen, IONIS</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">-</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">TTR-L</span><sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> and </span>IONIS-APOCIII-L<sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. There are a number of factors that could cause a clinical study to fail or be delayed, including:</span></div>
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    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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>
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    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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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    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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 in the trial;</div></td>
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    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">we, or our partners, may decide, or regulators may require us, to conduct additional preclinical testing or clinical studies;</div></td>
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    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">enrollment in our clinical studies may be slower than we anticipate;</div></td>
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<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="zec5d125d380d4af68ebc0576d20f4a87">
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    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">we or our partners, including our independent clinical investigators, contract research organizations and other third-party service providers on which we rely, may not identify, recruit and train suitable clinical investigators at a sufficient number of study sites or timely enroll a sufficient number of study subjects in the clinical study;</div></td>
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    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">the institutional review board for a prospective site might withhold or delay its approval for the study;</div></td>
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    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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>
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<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="z5572639e181c410a954f87e3095e995d">
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    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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>
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<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="ze694db5873814b16a13acdf91c3ee16d">
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    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">a clinical study site may deviate from the protocol for the study;</div></td>
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    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">the cost of our clinical studies may be greater than we anticipate;</div></td>
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    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">our partners may decide not to exercise any existing options to license and conduct additional clinical studies for our medicines; and</div></td>
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<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="za49708856f33475e8032565fb61bb689">
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    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">the supply or quality of our medicines or other materials necessary to conduct our clinical studies may be insufficient, inadequate or delayed.</div></td>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The current COVID-19 Pandemic could make some of these factors more likely to occur.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In addition, our current medicines, including SPINRAZA, TEGSEDI and WAYLIVRA, 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 and other regulators to ask questions or take actions that could harm or delay our ability to develop and commercialize our medicines or increase our costs. For example, the FDA or other regulatory agencies could request, among other things, any of the following regarding one of our medicines: additional information or commitments before we can start or continue a clinical study, protocol amendments, increased safety monitoring, additional product labeling information, and post-approval commitments. This happened in connection with the conditional marketing approval for WAYLIVRA in the EU, as the EC is requiring us to conduct a post-authorization safety study to evaluate the safety of WAYLIVRA on thrombocytopenia and bleeding in FCS patients taking WAYLIVRA. We have an ongoing OLE extension study of WAYLIVRA in patients with FCS and an OLE study of TEGSEDI in patients with hATTR, and an early access program, or EAP, for WAYLIVRA. Adverse events or results from these studies or the EAPs could negatively impact our pending or future marketing approval applications for WAYLIVRA and TEGSEDI in patients with FCS or hATTR amyloidosis or the commercial opportunity for WAYLIVRA or TEGSEDI.</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;">Any failure or delay in the clinical studies, including the studies of tominersen, tofersen, pelacarsen, IONIS</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">-</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">TTR-L</span><sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> and </span>IONIS-APOCIII-L<sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, could reduce the commercial potential or viability of our medicines.</span></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 our 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;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">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 Pharmaceutical Research Associates, Inc., Icon Clinical Research Limited, Syneos Health, Inc., PPD and Medpace for the clinical studies for our medicines, including tominersen, tofersen, pelacarsen, IONIS</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">-</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">TTR-L</span><sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> and </span>IONIS-APOCIII-L<sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. 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. However, we are responsible for ensuring that these third parties 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. The failure of these third parties to carry out their obligations</span>, including as a result of delays or disruption caused by the current COVID-19 Pandemic that may affect the third party&#8217;s ability to conduct the clinical studies for our medicines,<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> or a termination of our relationship with these third parties could delay or prevent the development, marketing authorization and commercialization of our medicines or additional marketing authorizations for TEGSEDI and WAYLIVRA.</span></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 many 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/or funding many of the medicines in our development pipeline. For example, we are relying on:</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;">Roche for development and funding of tominersen;</div></td>
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    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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; and</div></td>
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    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Biogen for development and funding of tofersen.</div></td>
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<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/or 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, as part of a reprioritization of its pipeline and strategic review of its rare disease business, GSK declined its option to license TEGSEDI and IONIS-FB-L<sub>Rx</sub>.</div>
<div><br /></div>
<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Even with funding from corporate partners, if our partners do not effectively perform their obligations under our agreements with them, it would delay or stop the progress of our drug development and commercial programs.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In addition to receiving funding, we enter into collaborative arrangements with third parties to:</div>
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    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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>
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    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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 authorization; and</div></td>
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<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="zf9bae3431f8942d0bac93e4009449438">
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    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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, market and sell our medicines.</div></td>
  </tr>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Once we have secured a collaborative arrangement to further develop and commercialize one of our drug development programs, such as our collaborations with AstraZeneca, Bayer, Biogen, GSK, Janssen, Novartis, Pfizer and Roche, these collaborations may not continue or result in commercialized medicines, or may not progress as quickly as we first anticipated.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">For example, a collaborator such as AstraZeneca, Bayer, Biogen, GSK, Janssen, Novartis, Pfizer or Roche, could determine that it is in its financial interest to:</div>
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<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="ze81eb4be70154f9cb8a4cfdb85da1da0">
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    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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>
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  <tr>
    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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>
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<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="z57eb0c888d6340c1be982908e76b469c">
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    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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 for its own medicines.</div></td>
  </tr>
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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;">If any of these occur, it could affect our partner&#8217;s commitment to the collaboration with us and could delay or otherwise negatively affect the commercialization of our medicines, including SPINRAZA, tominersen, pelacarsen and tofersen.</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;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">For planning purposes, we estimate and may disclose the timing of a variety of clinical, regulatory and other milestones, such as when we anticipate a certain medicine will enter clinical trials, when we anticipate completing a clinical study, or when we anticipate filing an application for, or obtaining, marketing authorization, or when we or our partners plan to commercially launch a medicine. We base our estimates on present facts and a variety of assumptions, many of which are outside of our control, including the current COVID-19 Pandemic. If we do not achieve milestones in accordance with our or our investors&#8217; or securities analysts&#8217; expectations, including milestones related to SPINRAZA, TEGSEDI, WAYLIVRA, tominersen, tofersen, pelacarsen, IONIS</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">-</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">TTR-L</span><sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> and </span>IONIS-APOCIII-L<sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, the price of our securities could decrease.</span></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 results</div>
<div><br /></div>
<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">We have incurred losses, and our business will suffer if we fail to consistently achieve profitability in the future.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Because drug discovery and development requires 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, 2020, we had an accumulated deficit of approximately $1.2 billion and stockholders&#8217; equity of approximately $0.8 billion. Most of our historical losses resulted from costs incurred in connection with our research and development programs and from selling, general and administrative costs associated with our operations. Most of our income has come from collaborative arrangements, including commercial revenue from royalties and R&amp;D revenue, with additional income from the sale or licensing of our patents, as well as interest income. If we do not continue to earn substantial revenue, we may incur additional operating losses in the future. We may not successfully develop any additional products or achieve or sustain future profitability.</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 drug programs will require significant additional research, development, manufacturing, preclinical and clinical testing, marketing authorization, preclinical activities and commitment of significant additional resources prior to their successful commercialization. These activities will require significant cash. As of December 31, 2020, we had cash, cash equivalents and short-term investments equal to $1.9 billion. If we or our partners do not meet our goals to successfully commercialize our medicines, including SPINRAZA, TEGSEDI and WAYLIVRA, or to license certain medicines and proprietary technologies, we will need additional funding in the future. Our future capital requirements will depend on many factors, such as the following:</div>
<div><br /></div>
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    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">successful commercialization of SPINRAZA, TEGSEDI and WAYLIVRA;</div></td>
  </tr>
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<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="z540c641402954d0c9cea7ebff038017a">
  <tr>
    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">additional marketing approvals for WAYLIVRA and TEGSEDI;</div></td>
  </tr>
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<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="zebd4ea45df1e4bc197b1f098a47a3253">
  <tr>
    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">the profile and launch timing of our medicines, including TEGSEDI and WAYLIVRA;</div></td>
  </tr>
</table>
<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="z5c75ce6acd4a4f778c6dddd776ea2d02">
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    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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;">the results of the clinical studies of tominersen, tofersen, pelacarsen, IONIS</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">-</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">TTR-L</span><sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> and </span>IONIS-APOCIII-L<sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">;</span></div></td>
  </tr>
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  <tr>
    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">changes in existing collaborative relationships and our ability to establish and maintain additional collaborative arrangements;</div></td>
  </tr>
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<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="ze54877437beb4a67bd32016dafcaae3c">
  <tr>
    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">continued scientific progress in our research, drug discovery and development programs;</div></td>
  </tr>
</table>
<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="ze6d708e083654986b14d11a3561e2654">
  <tr>
    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">the size of our programs and progress with preclinical and clinical studies;</div></td>
  </tr>
</table>
<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="zd690a063cfcc4e558355d010d2028254">
  <tr>
    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">the time and costs involved in obtaining marketing authorizations; and</div></td>
  </tr>
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  <tr>
    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">competing technological and market developments, including the introduction by others of new therapies that address our markets.</div></td>
  </tr>
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<div><br /></div>
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<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span>55</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;">If we need additional funds, we may need to raise them through public or private financing. Additional financing may not be available at all or on acceptable terms. If we raise additional funds by issuing equity securities, the shares of existing stockholders will be diluted and the price, as well as the price of our other securities, may decline. If adequate funds are not available or not available on acceptable terms, we may have to cut back on one or more of our research, drug discovery or development programs. Alternatively, we may obtain funds through arrangements with collaborative partners or others, which could require us to give up rights to certain of our technologies or medicines.</div>
<div><br /></div>
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Risks related to our intellectual property</div>
<div><br /></div>
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">If we cannot protect our patent rights or our other proprietary rights, others may compete more effectively against us.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our success depends to a significant degree upon whether we can continue to develop, secure and maintain intellectual property rights to proprietary products and services. However, we may not receive issued patents on any of our pending patent applications in the U.S. or in other countries and we may not be able to obtain, maintain or enforce our patents and other intellectual property rights 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>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We cannot be certain that the U.S. Patent and Trademark Office, or U.S. PTO, and courts in the U.S. or the patent offices and courts in foreign countries will consider the claims in our patents and applications covering SPINRAZA, TEGSEDI, WAYLIVRA, 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, including through legal action.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">If we or any licensor partner loses or cannot obtain patent protection for SPINRAZA, TEGSEDI, WAYLIVRA, or any of our other medicines in development, it could have a material adverse impact on our business.</div>
<div><br /></div>
<div style="text-align: justify; 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>
<div><br /></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>
<div><br /></div>
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<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span>56</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;">Risks related to our business strategy and personnel</div>
<div><br /></div>
<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">If we fail to successfully integrate Akcea&#8217;s business and operations, it may adversely affect our future results.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We believe our Akcea Acquisition will result in certain benefits, including a single vision and set of strategic priorities, led by one team, accelerating our next phase of growth and positioning us to more effectively deliver our medicines to patients. Under this transaction, Ionis will now retain more value from Akcea&#8217;s pipeline and commercial products, further strengthening our financial position and supporting continued investments in our future. The success of the transaction will depend on our ability to realize these anticipated benefits. We may fail to realize the anticipated benefits of the Akcea Acquisition for a variety of reasons, including the following:</div>
<div><br /></div>
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    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">failure to successfully manage relationships with partners, customers, distributors and suppliers;</div></td>
  </tr>
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    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">disruptions to Akcea&#8217;s commercial operations;</div></td>
  </tr>
</table>
<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="z6ca5e8bebd9e4ecb878a102c88ce8b8f">
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    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">potential incompatibility of technologies and systems;</div></td>
  </tr>
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<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="z70738c1ebfee45fb9bedfcdb12e03a3b">
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    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">failure to leverage the capabilities of the combined company quickly and effectively;</div></td>
  </tr>
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<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="z41ea6884992a42f08322340c6ea2566b">
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    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">potential difficulties integrating and harmonizing business systems and processes;</div></td>
  </tr>
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<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="zea074c1de0b64d579813caeddc8fc6fb">
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    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">tax benefits of the combined structure may not be available or in the expected amounts; and</div></td>
  </tr>
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<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="zce656d605b5540c88d0b06d6e9a4366a">
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    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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 loss of key employees.</div></td>
  </tr>
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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;">If our management transition is not successful our business could suffer.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In January 2020, Dr. Crooke, our founder and Chief Executive Officer, transitioned from Chief Executive Officer to Executive Chairman of our Board of Directors. As Executive Chairman, Dr. Crooke continues to be responsible for the activities of the board and remains active in the company, providing strategic advice and continuing to participate in the scientific activities. Starting in January 2020, Dr. Monia, who had been our Chief Operating Officer from January 2018 to January 2020 and has been a member of our team since our founding over 30 years ago, serves as our Chief Executive Officer. Following our 2021 Annual Meeting of Stockholders in June, Dr. Crooke will retire from Ionis and its board of directors but will continue to serve as a scientific advisor. If this transition is not successful, our business could suffer.</div>
<div><br /></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>
<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 dependent on the principal members of our management and scientific staff. We do not have employment agreements with any of our executive officers that would prevent them from leaving us. The loss of our management and key scientific employees might slow the achievement of important research and development goals. It is also critical to our success that we recruit and retain qualified scientific personnel to perform research and development work. We may not be able to attract and retain skilled and experienced scientific personnel on acceptable terms because of intense competition for experienced scientists among many pharmaceutical and health care companies, universities and non-profit research institutions. In addition, failure to succeed in clinical studies may make it more challenging to recruit and retain qualified scientific personnel. Similarly, if we cannot recruit and retain qualified </span>marketing, sales and distribution personnel, our ability to effectively implement our new commercial strategy following the Akcea Acquisition will be adversely affected.</div>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Risks related to taxes</div>
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<div style="text-align: left; 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>
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<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 that provision, we can carryforward our NOLs to offset our future taxable income, if any, until such NOLs are used or expire. The same is true of other unused tax attributes, such as tax credits.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Under the Tax Cut and Jobs Act of 2017, or the Tax Act, as modified by the Coronavirus Aid, Relief, and Economic Security Act, or the CARES Act, U.S. federal net operating losses incurred in 2018 and in future years may be carried forward indefinitely, but the deductibility of such U.S. federal net operating losses is limited to 80 percent of taxable income beginning in 2021. It is uncertain if and to what extent various states will conform to the federal Tax Act or the CARES Act. The CARES Act also reinstated the net operating loss carryback provisions whereby net operating losses incurred in calendar tax years 2018, 2019 and 2020 may be carried back to offset taxable income of the five tax years preceding the year of the loss.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">At the state level, there may be periods during which the use of net operating losses is suspended or otherwise limited, which could accelerate or permanently increase state taxes owed. For example, in June 2020, California enacted Assembly Bill 85 (AB 85), which suspends NOLs and limits credit utilization to $5 million per year for the 2020, 2021 and 2022 tax years. AB 85 did not have a material impact on our 2020 tax provision, but it is possible that it may in future years.</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, 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 percent change, by value, in its equity ownership over a three-year period, the corporation&#8217;s ability to use its pre-change net operating loss 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 net operating loss carryforwards or other tax attributes is materially limited, it would harm our future operating results by effectively increasing our future tax obligations. As a result of the Akcea Acquisition, we will be subject to the Separate Return Limitation Year, or SRLY, Rules. Under SRLY, our utilization of Akcea&#8217;s pre-acquisition net operating loss and tax credit carryforwards will be limited to the amount of income that Akcea contributes to our consolidated taxable income. The Akcea pre-acquisition tax attributes cannot be used to offset any of the income that Ionis contributes to our consolidated taxable income.</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 assessed our valuation allowances requirements, both federal and state, due to the Akcea Acquisition, and have also assessed whether Akcea may rejoin our consolidated tax group. For details regarding these assessments, see Note 5, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Income Taxes,</span> in the Notes to the Consolidated Financial Statements.</div>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Our future taxable income could be impacted by changes in tax laws, regulations and treaties.</div>
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<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>
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<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>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We are subject to U.S. federal, state, local and sales taxes in the U.S. and foreign income taxes, withholding taxes and transaction taxes in foreign jurisdictions. Significant judgment is required in evaluating our tax positions and our worldwide provision for taxes. During the ordinary course of business, there are many activities and transactions for which the ultimate tax determination is uncertain. In addition, our tax obligations and effective tax rates could be adversely affected by changes in the relevant tax, accounting and other laws, regulations, principles and interpretations, including those relating to income tax nexus, by recognizing tax losses or lower than anticipated earnings in jurisdictions where we have lower statutory rates and higher than anticipated earnings in jurisdictions where we have higher statutory rates, by changes in foreign currency exchange rates, or by changes in the valuation of our deferred tax assets and liabilities. We may be audited in various jurisdictions, and such jurisdictions may assess additional taxes, sales taxes and value-added taxes against us. Although we believe our tax estimates are reasonable, the final determination of any tax audits or litigation could be materially different from our historical tax provisions and accruals, which could have a material adverse effect on our operating results or cash flows in the period for which a determination is made.</div>
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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;">General risk factors</div>
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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">If the price of our securities continues to be highly volatile, this could make it harder for you 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, 2020, the market price of our common stock ranged from $64.34 to $39.32 per share. Many factors can affect the market price of our securities, including, for example, fluctuations in our operating results, announcements of collaborations, clinical study results, technological innovations or new products being developed by us or our competitors, the commercial success of our approved medicines, governmental regulation, marketing authorizations, changes in payers&#8217; reimbursement policies, developments in patent or other proprietary rights and public concern regarding the safety of our medicines.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">The current COVID-19 Pandemic has caused a </span>significant disruption of global financial markets and has resulted in increased volatility in the trading price of our common stock. Additionally, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">broad market and industry factors may also materially harm the market price of our common stock irrespective of our operating performance. The stock market in general, and NASDAQ and the market for biotechnology companies in particular, have 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 which 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.</span></div>
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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Provisions in our certificate of incorporation, convertible notes documents, call spread hedge transaction documents and Delaware law may prevent stockholders from receiving a premium for their shares.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our certificate of incorporation provides for classified terms for the members of our board of directors. Our certificate also includes a provision that requires at least 66 2/3 percent of our voting stockholders to approve a merger or certain other business transactions with, or proposed by, any holder of 15 percent or more of our voting stock, except in cases where certain directors approve the transaction or certain minimum price criteria and other procedural requirements are met.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our certificate of incorporation also requires that any action required or permitted to be taken by our stockholders must be taken at a duly called annual or special meeting of stockholders and may not be taken by written consent. In addition, only our board of directors, chairman of the board or chief executive officer can call special meetings of our stockholders. We have in the past, and may in the future, implement a stockholders&#8217; rights plan, also called a poison pill, which could make it uneconomical for a third party to acquire our company on a hostile basis. In addition, our board of directors has the authority to fix the rights and preferences of, and issue shares of preferred stock, which may have the effect of delaying or preventing a change in control of our company without action by our stockholders.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The provisions of our convertible senior notes could make it more difficult or more expensive for a third party to acquire us. Upon the occurrence of certain transactions constituting a fundamental change, holders of the notes will have the right, at their option, to require us to repurchase all of their notes or a portion of their notes, which may discourage certain types of transactions in which our stockholders might otherwise receive a premium for their shares over the then current market prices.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In December 2019, we entered into privately negotiated exchange and/or subscription agreements with certain new investors and certain holders of our existing 1% Notes to exchange $375.6 million of our 1% Notes for $439.3 million of our 0.125% Notes, and to issue $109.5 million of our 0.125% Notes. Additionally, in connection with the pricing of our 0.125% Notes, we entered into call spread transactions in which we purchased note hedges and sold warrants. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Terminating or unwinding the call spread transactions could require us to make substantial payments to the counterparties under those agreements or may increase our stock price. The costs or any increase in stock price that may arise from terminating or unwinding such agreements could make an acquisition of our company significantly more expensive to the purchaser.</span></div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">These provisions, as well as Delaware law, including Section 203 of the Delaware General Corporation Law, and other of our agreements, may discourage certain types of transactions in which our stockholders might otherwise receive a premium for their shares over then current market prices, and may limit the ability of our stockholders to approve transactions that they think may be in their best interests.</div>
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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Future sales of our common stock in the public market could adversely affect the trading price of our securities.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Future sales of substantial amounts of our common stock in the public market, or the perception that such sales could occur, could adversely affect trading prices of our securities. For example, we may issue approximately 11.2 million shares of our common stock upon conversion of our convertible senior notes and up to 6.6 million shares may be issued in connection with the warrant transactions we entered into in connection with the issuance of our 0.125% Notes, in each case subject to customary anti-dilution adjustments. The addition of any of these shares into the public market may have an adverse effect on the price of our securities.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In addition, pursuant to the call spread transactions we entered into in connection with the pricing of our 0.125% 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 0.125% Notes or offset any cash payments we are required to make in excess of the principal amount of the converted 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;">We are exposed to potential product liability claims, and insurance against these claims may not be available to us at a reasonable rate in the future or at all.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our business exposes us to potential product liability risks that are inherent in the testing, manufacturing, marketing and sale of therapeutic products, including potential product liability claims related to SPINRAZA, TEGSEDI and WAYLIVRA, and our medicines in development. We have clinical study insurance coverage and commercial product liability insurance coverage. However, this insurance coverage may not be adequate to cover claims against us, or be available to us at an acceptable cost, if at all. Regardless of their merit or eventual outcome, product liability claims may result in decreased demand for our medicines, injury to our reputation, withdrawal of clinical study volunteers and loss of revenues. Thus, whether or not we are insured, a product liability claim or product recall may result in losses that could be material.</div>
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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">We are dependent on information technology systems, infrastructure and data, which exposes us to data security risks.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We are dependent upon our own and third-party information technology systems, infrastructure and data, including mobile technologies, to operate our business. The multitude and complexity of our computer systems may make them vulnerable to service interruption or destruction, disruption of data integrity, malicious intrusion, or random attacks. Likewise, data privacy or security incidents or breaches by employees or others may pose a risk that sensitive data, including our intellectual property, trade secrets or personal information of our employees, patients, customers or other business partners may be exposed to unauthorized persons or to the public. Cyber-attacks are increasing in their frequency, sophistication and intensity, with third-party phishing and social engineering attacks in particular increasing in connection with the COVID-19 Pandemic. Cyber-attacks could include the deployment of harmful malware, denial-of-service, social engineering and other means to affect service reliability and threaten data confidentiality, integrity and availability. Our business partners face similar risks and any security breach of their systems could adversely affect our security posture. A security breach or privacy violation that leads to disclosure or modification of or prevents access to patient information, including personally identifiable information or protected health information, could harm our reputation, compel us to comply with federal and state breach notification laws and foreign law equivalents, subject us to financial penalties and mandatory and costly corrective action, require us to verify the correctness of database contents and otherwise subject us to litigation or other liability under laws and regulations that protect personal data, any of which could disrupt our business and result in increased costs or loss of revenue. Moreover, the prevalent use of mobile devices that access confidential information increases the risk of data security breaches, which could lead to the loss of confidential information, trade secrets or other intellectual property. While we have invested, and continue to invest, in the protection of our data and information technology infrastructure, our efforts may not prevent service interruptions, or identify breaches in our systems, that could adversely affect our business and operations and result in the loss of critical or sensitive information, which could result in financial, legal, business or reputational harm to us. In addition, our liability insurance may not be sufficient in type or amount to cover us against claims related to security breaches, cyber-attacks and other related breaches.</div>
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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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    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">interruption of our research, development and manufacturing efforts;</div></td>
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    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">injury to our employees and others;</div></td>
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    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">environmental damage resulting in costly clean up; and</div></td>
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    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">liabilities under federal, state and local laws and regulations governing health and human safety, as well as the use, storage, handling and disposal of these materials and resultant waste products.</div></td>
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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 in amounts and types that we consider commercially reasonable, we do not have insurance coverage for losses relating to an interruption of our research, development or manufacturing efforts caused by contamination, and 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>
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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">If a natural or man-made disaster strikes our research, development or manufacturing facilities or otherwise affects our business, it could delay our progress developing and commercializing our medicines.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We manufacture most of our research and clinical supplies in a manufacturing facility located in Carlsbad, California. We manufacture the finished drug product for TEGSEDI and WAYLIVRA at third-party contract manufacturers. Biogen manufactures the finished drug product for SPINRAZA. The facilities and the equipment we, our partners and our contract manufacturers use to research, develop and manufacture our medicines would be costly to replace and could require substantial lead time to repair or replace. Our facilities or those of our partners or contract manufacturers may be harmed by natural or man-made disasters, including, without limitation, earthquakes, floods, fires, acts of terrorism and pandemics; and if such facilities are affected by a disaster, our development and commercialization efforts would be delayed. Although we possess property damage and business interruption insurance coverage, this insurance may not be sufficient to cover all of our potential losses and may not continue to be available to us on acceptable terms, or at all. In addition, our development and commercialization activities could be harmed or delayed by a shutdown of the U.S. government, including the FDA.</div>
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<div style="text-align: 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>
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<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 controls systems in order 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>
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<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. On July 21, 2010, the Dodd-Frank Wall Street Reform and Protection Act, or the Dodd-Frank Act, was enacted. There are significant corporate governance and executive compensation-related provisions in the Dodd-Frank Act that require the SEC to adopt, or where the SEC has adopted, additional rules and regulations in these areas such as &#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 may lead to additional compliance costs and impact the manner in which we operate our business.</div>
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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Negative conditions in the global credit markets and financial services and other industries may adversely affect our business.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The global credit markets, the financial services industry, the U.S. capital markets, and the U.S. economy as a whole are currently experiencing substantial turmoil and uncertainty characterized by unprecedented intervention by the U.S. federal government in response to the COVID-19 Pandemic. In the past, the failure, bankruptcy, or sale of various financial and other institutions created similar turmoil and uncertainty in such markets and industries. It is possible that a crisis in the global credit markets, the U.S. capital markets, the financial services industry or the U.S. economy may adversely affect our business, vendors and prospects, as well as our liquidity and financial condition. More specifically, 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; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">A variety of risks associated with operating our business and marketing our medicines internationally could adversely affect our business<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">.</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 addition to our U.S. operations, we are commercializing TEGSEDI in the EU and Canada, and WAYLIVRA in the EU. We face risks associated with our international operations, including possible unfavorable regulatory, pricing and reimbursement, political, tax and labor conditions, which could harm our business. Because we have international operations we are subject to numerous risks associated with international business activities, including:</div>
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    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">compliance with differing or unexpected regulatory requirements for our medicines and foreign employees;</div></td>
  </tr>
</table>
<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="zc59b3cc1060f460887ee21d15847b5b6">
  <tr>
    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">complexities associated with managing multiple payer reimbursement regimes, government payers or patient self-pay systems;</div></td>
  </tr>
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<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="z2be734573b9c45d290932cac88bbccec">
  <tr>
    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">difficulties in staffing and managing foreign operations;</div></td>
  </tr>
</table>
<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="z62e97ad1045645e3b860fb115f2eee33">
  <tr>
    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">in certain circumstances, increased dependence on the commercialization efforts and regulatory compliance of third-party distributors or strategic partners;</div></td>
  </tr>
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<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="z6cb8055e6820496fbd20c52c52f3cf37">
  <tr>
    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">foreign government taxes, regulations and permit requirements;</div></td>
  </tr>
</table>
<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="z3f81571757394351853671cb26f23fd6">
  <tr>
    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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;">U</span>.S. and foreign government tariffs, trade restrictions, price and exchange controls and other regulatory requirements;</div></td>
  </tr>
</table>
<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="zd88fc0503ca240b09e46cadb6c50516e">
  <tr>
    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">anti-corruption laws, including the Foreign Corrupt Practices Act, or the FCPA, and its equivalent in foreign jurisdictions;</div></td>
  </tr>
</table>
<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="z80a8a9e9d1474e168ca6a02074136e8c">
  <tr>
    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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;">economic weakness, including inflation, natural disasters, war, events of terrorism, political instability or public </span>health issues or pandemics, such as the current COVID-19 Pandemic, in particular foreign countries or globally;</div></td>
  </tr>
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<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="zd600d2d278a740bd8aff733747159f45">
  <tr>
    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">fluctuations in currency exchange rates, which could result in increased operating expenses and reduced revenue, and other obligations related to doing business in another country;</div></td>
  </tr>
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<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="z715b39f7500d4d71bfb17051554e806b">
  <tr>
    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">compliance with tax, employment, privacy, immigration and labor laws, regulations and restrictions for employees living or traveling abroad;</div></td>
  </tr>
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<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="z52914f9695dd4f9e8982e3b82aa8d50c">
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    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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>
  </tr>
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<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="zea93035ac8be4fe2a322bb40ef730614">
  <tr>
    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">changes in diplomatic and trade relationships.</div></td>
  </tr>
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<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The United Kingdom&#8217;s exit from the E.U. could increase these risks.</div>
<div><br /></div>
<div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
<div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span>61</span></div>
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<div style="page-break-after:always;"><hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>
<div></div>
</div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our business activities outside of the U.S. are subject to the FCPA and similar anti-bribery or anti-corruption laws, regulations or rules of other countries in which we operate, including the United Kingdom&#8217;s Bribery Act 2010. In many other countries, the healthcare providers who prescribe pharmaceuticals are employed by their government, and the purchasers of pharmaceuticals are government entities; therefore, any dealings with these prescribers and purchasers may be subject to regulation under the FCPA. There is no certainty that all employees and third-party business partners (including our distributors, wholesalers, agents, contractors and other partners) will comply with anti-bribery laws. In particular, we do not control the actions of manufacturers and other third-party agents, although we may be liable for their actions. Violation of these laws may result in civil or criminal sanctions, which could include monetary fines, criminal penalties, and disgorgement of past profits, which could have an adverse impact on our business and financial condition.</div>
<div><br /></div>
<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">The impact on us of the vote by the United Kingdom to leave the European Union cannot be predicted.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The withdrawal of the UK from the EU, commonly referred to as &#8220;Brexit,&#8221; may adversely impact our ability to obtain regulatory approvals of our medicines in the EU, result in restrictions or imposition of taxes and duties for importing our medicines into the EU, and may require us to incur additional expenses in order to develop, manufacture and commercialize our medicines in the EU.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Following the result of a referendum in 2016, the UK left the EU on January 31, 2020. Pursuant to the formal withdrawal arrangements agreed between the UK and the EU, the UK was subject to a transition period that ended December 31, 2020, or the Transition Period, during which EU rules continued to apply. A trade and cooperation agreement, or the Trade and Cooperation Agreement, that outlines the future trading relationship between the UK and the EU was agreed in December 2020.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Since a significant proportion of the regulatory framework in the UK applicable to our business and our medicines is derived from EU directives and regulations, Brexit has had, and may continue to have, a material impact upon the regulatory regime with respect to the development, manufacture, importation, approval and commercialization of our medicines in the UK or the EU. For example, Great Britain is no longer covered by the centralized procedures for obtaining EU-wide marketing authorization from the EMA and, and a separate marketing authorization will be required to market our medicines in Great Britain. It is currently unclear whether the Medicines &amp; Healthcare products Regulatory Agency in the UK is sufficiently prepared to handle the increased volume of marketing authorization applications that it is likely to receive. Any delay in obtaining, or an inability to obtain, any marketing approvals, as a result of Brexit or otherwise, would delay or prevent us from commercializing our medicines in the UK or the EU.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">While the Trade and Cooperation Agreement provides for the tariff-free trade of medicinal products between the UK and the EU, there may be additional non-tariff costs to such trade which did not exist prior to the end of the Transition Period. Further, should the UK diverge from the EU from a regulatory perspective in relation to medicinal products, tariffs could be put into place in the future. We could therefore, both now and in the future, face significant additional expenses (when compared to the position prior to the end of the Transition Period) to operate our business.</div>
<div><br /></div>
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">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;">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 18, 2021, the following are the primary facilities in which we operate:</div>
<div><br /></div>
<table cellpadding="0" cellspacing="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" id="zad66f39c58904296b30840e68a2bf41a">
  <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: 12.55%; vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Location</div></td>
    <td style="width: 2.18%; vertical-align: top;">&#160;</td>
    <td style="width: 9.77%; vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Square</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Footage</div></td>
    <td style="width: 2.18%; vertical-align: top;">&#160;</td>
    <td style="width: 10.38%; vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Owned</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">or Leased</div></td>
    <td style="width: 2.18%; vertical-align: top;">&#160;</td>
    <td style="width: 14.52%; vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Initial Lease</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Term End Date</div></td>
    <td style="width: 2.18%; vertical-align: top;">&#160;</td>
    <td style="width: 22.22%; vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Lease</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Extension Options</div></td>
  </tr>
  <tr>
    <td style="width: 19.66%; vertical-align: bottom; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Laboratory and office space facility</div></td>
    <td style="width: 2.18%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 12.55%; vertical-align: bottom; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Carlsbad, CA</div></td>
    <td style="width: 2.18%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 9.77%; vertical-align: bottom; background-color: #CCEEFF;"><div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">176,000</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;">Office and meeting space facility</div></td>
    <td style="width: 2.18%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 12.55%; vertical-align: bottom; background-color: #FFFFFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Carlsbad, CA</div></td>
    <td style="width: 2.18%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 9.77%; vertical-align: bottom; background-color: #FFFFFF;"><div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">74,000</div></td>
    <td style="width: 2.18%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 10.38%; vertical-align: bottom; background-color: #FFFFFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Owned</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;">&#160;</td>
    <td style="width: 2.18%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 22.22%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
  </tr>
  <tr>
    <td style="width: 19.66%; vertical-align: bottom; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Office space facility</div></td>
    <td style="width: 2.18%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 12.55%; vertical-align: bottom; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Boston, MA</div></td>
    <td style="width: 2.18%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 9.77%; vertical-align: bottom; background-color: #CCEEFF;"><div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">30,175</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;">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; 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: #FFFFFF;">&#160;</td>
    <td style="width: 12.55%; vertical-align: bottom; background-color: #FFFFFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Carlsbad, CA</div></td>
    <td style="width: 2.18%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 9.77%; vertical-align: bottom; background-color: #FFFFFF;"><div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">26,800</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;">Owned</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;">&#160;</td>
    <td style="width: 2.18%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 22.22%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
  </tr>
  <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 support facility</div></td>
    <td style="width: 2.18%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 12.55%; vertical-align: bottom; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Carlsbad, CA</div></td>
    <td style="width: 2.18%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 9.77%; vertical-align: bottom; background-color: #CCEEFF;"><div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">25,800</div></td>
    <td style="width: 2.18%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 10.38%; vertical-align: bottom; background-color: #CCEEFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Leased</div></td>
    <td style="width: 2.18%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 14.52%; vertical-align: bottom; background-color: #CCEEFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2026</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; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Office and storage space facility</div></td>
    <td style="width: 2.18%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 12.55%; vertical-align: bottom; background-color: #FFFFFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Carlsbad, CA</div></td>
    <td style="width: 2.18%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 9.77%; vertical-align: bottom; background-color: #FFFFFF;"><div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">18,700</div></td>
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    <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;">2023</div></td>
    <td style="width: 2.18%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 22.22%; vertical-align: bottom; background-color: #FFFFFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">One, five-year option to extend</div></td>
  </tr>
  <tr>
    <td style="width: 19.66%; vertical-align: bottom; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Office space facility</div></td>
    <td style="width: 2.18%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 12.55%; vertical-align: bottom; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Carlsbad, CA</div></td>
    <td style="width: 2.18%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
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    <td style="width: 10.38%; vertical-align: bottom; background-color: #CCEEFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Leased</div></td>
    <td style="width: 2.18%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 14.52%; vertical-align: bottom; background-color: #CCEEFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2023</div></td>
    <td style="width: 2.18%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 22.22%; vertical-align: bottom; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">One, five-year option to extend</div></td>
  </tr>
  <tr>
    <td style="width: 19.66%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 2.18%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 12.55%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 2.18%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
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    <td style="width: 2.18%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 10.38%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 2.18%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 14.52%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 2.18%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 22.22%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
  </tr>
</table>
<div><br /></div>
<div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
<div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span>62</span></div>
</div>
<div style="page-break-after:always;"><hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>
<div></div>
</div>
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">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, see Note 9, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Legal Proceedings,</span> in the Notes to the Consolidated Financial Statements.</div>
<div><br /></div>
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Item 4. Mine Safety Disclosures</div>
<div><br /></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Not applicable.</div>
<div><br /></div>
<div><br /></div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">PART II</div>
<div><br /></div>
<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;">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 18, 2021, there were approximately 506 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, 2015 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 src="image09.jpg" width="554" height="460" alt="graphic" /></div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">*&#160; $100 invested on December 31, 2015 in stock or index, including reinvestment of dividends. Fiscal year ending December 31.</div>
<div><br /></div>
<div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
<div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span>63</span></div>
</div>
<div style="page-break-after:always;"><hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>
<div></div>
</div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">COMPARISON OF 5 YEAR CUMULATIVE TOTAL RETURN</div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Among Ionis Pharmaceuticals, Inc., the Nasdaq Composite Index,</div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">and the Nasdaq Biotechnology Index</div>
<div style="text-align: center;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> </span><br /></div>
<table cellpadding="0" cellspacing="0" id="z78897ea08934461991823cc7b0056219" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
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    <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;"></div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Dec-15</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Dec-16</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Dec-17</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Dec-18</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Dec-19</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Dec-20</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#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 colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">100.00</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">77.23</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">81.22</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">87.29</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">97.55</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">91.30</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 28%; background-color: #FFFFFF;"><div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Nasdaq Composite Index</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">100.00</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">108.87</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">141.13</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">137.12</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">187.44</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">271.64</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 28%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Nasdaq Biotechnology Index</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">100.00</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">78.65</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">95.67</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">87.19</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">109.08</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">137.90</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
</table>
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">________________</div>
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  <tr>
    <td style="width: 36pt; vertical-align: top; align: right; 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;">Item 6. Selected Financial Data</div>
<div><br /></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Refer to our financial data contained within Item 7, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Management&#8217;s Discussion and Analysis</span>, our financial statements and within other parts of this document.</div>
<div><br /></div>
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><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, 2020, and our financial condition at December 31, 2020. Refer to our <a href="https://www.sec.gov/ix?doc=/Archives/edgar/data/874015/000114036120004500/form10k.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2019 Form 10-K for our results of operations for 2019 compared to 2018</a>. Except for the historical information contained herein, the following discussion contains forward-looking statements that are subject to known and unknown risks, uncertainties and other factors that may cause our actual results to differ materially from those expressed or implied by such forward-looking statements. We discuss such risks, uncertainties and other factors throughout this report and specifically under Item 1A of Part I of this report, &#8220;Risk Factors.&#8221; In addition, the following review should be read in conjunction with the information presented in our consolidated financial statements and the related notes to our consolidated financial statements as indexed on page F-1.</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 more than 30 years, we have been a leader in RNA-targeted therapy and believe our medicines are pioneering new markets, changing standards of care and transforming the lives of people with devastating diseases. We currently have three marketed medicines and a late-stage pipeline primarily focused on two core franchises: neurology and cardiometabolic. Our scientific innovation began and continues with the knowledge that sick people depend on us, which fuels our vision of becoming one of the most successful biotechnology companies. For further details on our business refer to the Business section of Part I of this report.</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;">Financial Highlights</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;">The following is a summary of our financial results (in millions):</div>
<div><br /></div>
<table cellpadding="0" cellspacing="0" id="z4210e8f0b97c42cbab8088b812147de1" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="6" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><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" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#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;"></div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2020</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2019</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#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 colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">729.3</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,122.6</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%;"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total operating expenses</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">901.3</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">756.7</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Income (loss) from operations</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(172.1</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">365.9</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net income (loss)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(486.8</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">303.3</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -8.85pt; margin-left: 8.85pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net income (loss) attributable to Ionis Pharmaceuticals, Inc. common stockholders</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(451.3</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">294.1</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Cash, cash equivalents and short-term investments</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,892.4</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2,499.5</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#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 revenue increased in 2020 compared to 2019 due to an increase in product sales from TEGSEDI and WAYLIVRA, primarily from major market launches in 2020. Our R&amp;D revenue in 2019 was higher compared to 2020 primarily because of license fees we recognized in 2019. In 2019, we earned approximately $400 million of revenue from licensing vupanorsen to Pfizer and pelacarsen to Novartis.</div>
<div><br /></div>
<div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
<div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span>64</span></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;">Our operating expenses for 2020 increased compared to 2019 principally due to our investments in the Phase 3 program for IONIS-TTR-L<sub>Rx</sub> and our wholly owned pipeline. Additionally, we incurred approximately $90 million in costs related to the Akcea Acquisition and restructured European operations. The costs primarily consisted of severance and retention costs of $29 million and stock-based compensation expense for the acceleration of Akcea equity awards of $59 million.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our net loss for 2020 included income tax expense of $317 million compared to $44 million in 2019. The increase was primarily due to a non-cash tax expense of $313 million related to an increase in the valuation allowance we recorded against our federal net deferred tax assets. As a result of the Akcea Acquisition, Ionis and Akcea will file their federal taxes on a consolidated basis beginning in the fourth quarter of 2020. We recorded a valuation allowance against all of Ionis&#8217; federal net deferred tax assets in the fourth quarter of 2020, due largely to Akcea&#8217;s history of losses, and the expected impact of this on Ionis&#8217; consolidated federal taxable income. We now maintain a valuation allowance against all our consolidated federal and state net deferred tax assets. See Note 5, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Income Taxes,</span> in the Notes to the Consolidated Financial Statements for further discussion on our valuation allowance assessment.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">With $1.9 billion in cash and short-term investments at December 31, 2020, we believe we have the financial resources to execute on our strategic priorities for 2021 and beyond.</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;">Business Segments</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Through 2020, we had two operating segments, our Ionis Core segment and Akcea Therapeutics. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Akcea was focused on developing and commercializing medicines to treat patients with serious and rare diseases. We have provided segment financial information and results for our Ionis Core segment and our Akcea Therapeutics segment based on the segregation of revenues and expenses that our chief decision maker reviewed to assess operating performance and to make operating decisions through 2020. We allocated a portion of Ionis&#8217; development, R&amp;D support and general and administrative expenses to Akcea for work Ionis performed on behalf of Akcea and we billed Akcea for these expenses.</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> As a result of acquiring Akcea in the fourth quarter of 2020 we integrated Akcea operations within Ionis. Beginning in 2021, our chief decision maker began assessing operating performance and making operating decisions on a single segment basis, which we refer to as Ionis Pharmaceuticals.</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;">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 United States. As such, we make certain estimates, judgments and assumptions that we believe are reasonable, based upon the information available to us. These judgments involve making estimates about the effect of matters that are inherently uncertain and may significantly impact our quarterly or annual results of operations and financial condition. Each quarter, our senior management reviews the development, selection and disclosure of such estimates with the audit committee of our board of directors. In the following paragraphs, we describe the specific risks associated with these critical accounting estimates and we caution that future events rarely develop exactly as one may expect, and that best estimates may require adjustment. Our significant accounting policies are outlined in Note 1, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Organization and Significant Accounting Policies</span>, in the Notes to the Consolidated Financial Statements.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following are our significant accounting estimates, which we believe are the most critical to aid in fully understanding and evaluating our reported financial results:</div>
<div><br /></div>
<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="zf88cd1dbe71e4ab6954b10aeb1fac5ec">
  <tr>
    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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>
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<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="zf13880e11d31475a93de051f663822a5">
  <tr>
    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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>
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<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="z2b9f41a769db4a379c0cedb2404680ca">
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    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Estimating our income taxes.</div></td>
  </tr>
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<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The 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. The following is a summary of the critical accounting estimates we make with respect to each of our significant revenue sources.</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;">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 estimate our commercial revenue from SPINRAZA royalties based on reporting we receive from Biogen each quarter. We use this reporting to calculate our royalty revenue based on our tiered contractual royalty rate for the given period based on annual cumulative net sales. We record our royalty revenue in the same period in which Biogen sells SPINRAZA. We also estimate commercial revenue from 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; font-style: italic;">Commercial Revenue: Product sales, net</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We added product sales from TEGSEDI to our commercial revenue in the fourth quarter of 2018 and we added product sales from WAYLIVRA to our commercial revenue in the third quarter of 2019. We recognize product sales in the period when our customer obtains control of our products. We record product sales at our net sales price, which includes estimated reserves for discounts, returns, chargebacks, rebates, co-pay assistance and other allowances that we offer under contracts between us and our customers, wholesalers, health care providers and other indirect customers. Actual amounts may vary from our estimates. Our historical reserve estimates have not been materially different from our actual amounts. The total reserves we estimated during 2020 and 2019 were not material to our financial results.</div>
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<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Research and development revenue under collaborative agreements</div>
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<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>
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<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="zb3a65bc5d60a4c7292804d91dca45e70">
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    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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>
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<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>
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<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="z3fbbc888a7e7418e85733a6a2af405ca">
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    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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>
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<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.</div>
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<div style="text-align: justify; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We are required to 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. For example, in the fourth quarter of 2020, we achieved a milestone payment for $7.5 million under our 2018 strategic neurology collaboration with Biogen. Prior to achieving this milestone payment, we did not consider this payment probable. Upon achieving the milestone payment, we reassessed the total transaction price of our 2018 strategic neurology collaboration. We added this milestone payment to our total transaction price under our collaboration.</div>
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<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="zae016f88e9c341d9a56e4e4d48143f6f">
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    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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>
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<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>
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<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. Each of these types of revenue require us to make various judgements and estimates.</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;">Amortization from Upfront Payments</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 revenue from the amortization of upfront payments as we perform R&amp;D services. We use an input method to estimate the amount of revenue to recognize each period. This method requires us to make estimates of the total costs we expect to incur to complete our R&amp;D services performance obligation or the total length of time it will take us to complete our R&amp;D services performance obligation. If we change our estimates, we may have to adjust our revenue. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Refer to Note 6, </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Collaborative Arrangements and Licensing Agreements</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, for further discussion of the cumulative catch up adjustment we made.</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;">Milestone Payments</div>
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<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>
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    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Whether the milestone payment is probable (discussed in detail above under &#8220;Determining the<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> transaction price, including any variable consideration&#8221;</span>); and</div></td>
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    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Whether the milestone payment relates to services we are performing or if our partner is performing the services:</div></td>
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    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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;Amortization of Upfront payments&#8221;).</div></td>
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    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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>
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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;">License Fees</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 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. 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;.</div>
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<div style="text-align: justify; text-indent: -18pt; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Estimated Liability for Clinical Development Costs</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We have numerous medicines in preclinical studies and/or clinical trials at clinical sites throughout the world. On at least a quarterly basis, we estimate our liability for preclinical and clinical development costs we have incurred and services that we have received but for which we have not yet been billed and maintain an accrual to cover these costs. These costs primarily relate to third-party clinical management costs, laboratory and analysis costs, toxicology studies and investigator grants. We estimate our liability using assumptions about study and patient activities and the related expected expenses for those activities determined based on the contracted fees with our service providers. The assumptions we use represent our best estimates of the activity and expenses at the time of our accrual and involve inherent uncertainties and the application of our judgment. Upon settlement, these costs may differ materially from the amounts accrued in our consolidated financial statements. Our historical accrual estimates have not been materially different from our actual amounts.</div>
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<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Income Taxes</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Ionis and Akcea have filed separate U.S. federal income tax returns since Akcea&#8217;s IPO in 2017. Accordingly, we were required to assess Ionis&#8217; stand-alone and Akcea&#8217;s valuation allowances separately even though we consolidate Akcea&#8217;s financial results in our consolidated financial statements. However, as a result of the Akcea Acquisition, Ionis and Akcea will file a consolidated U.S. federal income tax return beginning in the fourth quarter of 2020, and we therefore assessed our U.S. federal valuation allowance requirements on a consolidated basis as of that period. We continue to assess the state portion of our valuation allowance on a consolidated basis.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We assessed our valuation allowance requirements and recorded a valuation allowance of $313 million against all of Ionis&#8217; U.S. federal net deferred tax assets in the fourth quarter of 2020, due to uncertainties related to our ability to realize the tax benefits associated with these assets. This determination is based largely on Akcea rejoining the Ionis consolidated U.S. federal tax group in the fourth quarter of 2020. Due to Akcea&#8217;s historical and projected financial statement losses, and the expected negative impact this will have on Ionis&#8217; consolidated taxable income, there is uncertainty of generating sufficient consolidated pre-tax income in future periods to realize the Ionis deferred tax benefits. It is also expected that Ionis&#8217; pre-tax income in future periods may be lower due to significant investments in research and development associated with our pipeline of wholly owned medicines. We now maintain a valuation allowance against all our consolidated U.S. federal and state net 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;">We evaluate our deferred tax assets quarterly 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: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Results 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;">Below we have included our results of operations for 2020 compared to 2019. Refer to our 2019 Form 10-K for our results of operations for 2019 compared to 2018.</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;">Years Ended December 31, 2020 and December 31, 2019</div>
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<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Revenue</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total revenue for 2020 was $729.3 million compared to $1.1 billion in 2019 and was comprised of the following (amounts in millions):</div>
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<table cellpadding="0" cellspacing="0" id="z1f6890c4ba7a48259a53548cbcf80168" 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" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="6" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><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" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
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    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2020</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2019</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#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;">Revenue:</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>
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    <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 colspan="1" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>
  </tr>
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    <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 colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">286.6</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">293.0</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#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;">Product sales, net</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">70.0</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">42.3</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 2px; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -27pt; margin-left: 45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Licensing and other royalty revenue</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
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  <tr>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
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  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
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  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">86.0</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">489.7</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
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  <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 colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">16.4</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">19.3</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#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: 45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total R&amp;D revenue</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">364.6</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">770.1</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
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  <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: 81pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total revenue</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">729.3</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,122.6</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</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;">In 2020, our commercial revenue increased compared to 2019 primarily due to increases in TEGSEDI and WAYLIVRA product sales, primarily from major market launches in 2020.</div>
<div><br /></div>
<div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We earn our R&amp;D revenue from multiple sources. Our R&amp;D revenue can fluctuate depending on the timing of events. Our R&amp;D revenue in 2020 included more than $165 million from our cardiometabolic disease franchise, including a $75 million milestone payment we earned from Pfizer in the fourth quarter of 2020. We also earned more than $125 million from our neurological disease franchise, primarily driven by several Biogen-partnered programs. Additionally, in November 2020, we completed an arbitration process with Alnylam. The arbitration panel awarded us $41 million for payments owed to us by Alnylam related to Alnylam&#8217;s agreement with Sanofi Genzyme. We recognized the $41 million payment from Alnylam as R&amp;D revenue in the fourth quarter of 2020.</div>
</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our R&amp;D revenue in 2019 included significant revenue from license fees, including $246 million for Pfizer&#8217;s license of vupanorsen and $150 million for Novartis&#8217; license of pelacarsen. Additionally, our amortization from upfront payments for 2019 was higher compared to 2020 because it included amortization from collaborations for which we have completed our R&amp;D services performance obligations in 2019.</div>
<div><br /></div>
<div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
<div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span>68</span></div>
</div>
<div style="page-break-after:always;"><hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>
<div></div>
</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;">Operating expenses for 2020 were $901.3 million, and increased compared to $756.7 million for 2019. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">The increase was principally due to $89.6 million of operating expenses related to the Akcea Acquisition and restructured European operations, including non-cash </span>stock-based compensation expense of $59.3 million related to the acceleration of all of Akcea&#8217;s equity award stock-based compensation expense and severance, retention and other expenses of $30.3 million. Excluding expenses related to the Akcea Acquisition and restructured European operations, our operating expenses increased primarily <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">due to our investments in the Phase 3 program for IONIS-TTR-L</span><sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> and our wholly-owned pipeline.</span></div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our operating expenses by segment were as follows (in millions):</div>
<div><br /></div>
<table cellpadding="0" cellspacing="0" id="z7178e727d80c4c90aac65858ea89f609" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <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;"></div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="6" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><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" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2020</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2019</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#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;">Ionis Core</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">412.2</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">374.0</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#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;">Akcea Therapeutics</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">310.9</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">450.7</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#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;">Elimination of intercompany activity</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(51.9</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(214.6</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;"><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; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Subtotal</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">671.2</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">610.1</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#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 colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">230.1</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">146.6</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#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 operating expenses</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">901.3</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">756.7</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#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 order 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 Products Sold</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 products sold 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. Prior to the regulatory approval of TEGSEDI and WAYLIVRA, we expensed as R&amp;D expense a significant portion of the cost of producing TEGSEDI and WAYLIVRA that we are using in the commercial launches. We expect cost of products sold to increase as we deplete these inventories.</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 products sold by segment were as follows (in millions):</div>
<div><br /></div>
<table cellpadding="0" cellspacing="0" id="zf4aac84440ce42acb136e96da5111614" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <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;"></div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="6" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><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" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2020</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2019</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#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;">Ionis Core</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#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;">Akcea Therapeutics</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">18.9</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">12.8</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#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;">Elimination of intercompany activity</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(8.9</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(8.9</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;"><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; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Subtotal</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.0</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3.9</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#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 colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1.9</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.4</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#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 cost of products sold</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">11.9</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4.3</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#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 cost of products sold increased in 2020 compared to 2019 because of the increase in associated product sales in the same periods. In its cost of products sold, Akcea includes the amortization for milestone payments it made to us related to the U.S. and European approvals of TEGSEDI. We eliminate this amortization in our consolidated results. All amounts exclude non-cash compensation expense related to equity awards.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We began recognizing cost of products sold for TEGSEDI in the third quarter of 2018 when TEGSEDI was approved and for WAYLIVRA in the second quarter of 2019 when WAYLIVRA was approved. Our cost of products sold increased in 2020 compared to 2019 primarily due to the increase in product sales of TEGSEDI and WAYLIVRA. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">All amounts exclude non-cash compensation expense related to equity awards.</span></div>
<div><br /></div>
<div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
<div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span>69</span></div>
</div>
<div style="page-break-after:always;"><hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>
<div></div>
</div>
<div><br /></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Research, Development and Patent Expenses</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our research, development and patent expenses consist of expenses for antisense drug discovery, antisense drug development, manufacturing and development chemistry and R&amp;D support expenses.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following table sets forth information on research, development and patent expenses (in millions):</div>
<div><br /></div>
<table cellpadding="0" cellspacing="0" id="z33c2cb4277df4275a0dd2505351854dc" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <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;"></div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="6" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><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" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2020</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2019</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#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 colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">419.5</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">370.3</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#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 colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">115.6</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">95.4</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#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 colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">535.1</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">465.7</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#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 research, development and patent expenses by segment were as follows (in millions):</div>
<div><br /></div>
<table cellpadding="0" cellspacing="0" id="z4dbc306bdc9247e08672b446ea0bbce7" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <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;"></div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="6" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><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" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2020</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2019</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#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;">Ionis Core</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">325.4</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">295.0</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#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;">Akcea Therapeutics</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">137.1</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">281.0</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#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;">Elimination of intercompany activity</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(43.0</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(205.7</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;"><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; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Subtotal</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">419.5</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">370.3</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#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 colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">115.6</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">95.4</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#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 research, development and patent expenses</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">535.1</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">465.7</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>
  </tr>
</table>
<div><br /></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-decoration: underline;">Antisense 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 antisense technology 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 antisense drug discovery research, and that of our partners. Antisense drug discovery is also the function that is responsible for advancing our antisense core technology. This function is also responsible for making investments in complementary technologies to expand the reach of antisense technology.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">As we continue to advance our antisense technology, we are investing in our drug discovery programs to expand our pipeline.</div>
<div><br /></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our antisense drug discovery expenses are part of our Ionis Core business segment and were as follows (in millions):</div>
<div><br /></div>
<table cellpadding="0" cellspacing="0" id="z22ee05dace1a403dab83f7d770b98c80" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <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;"></div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="6" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><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" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2020</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2019</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#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;">Antisense drug discovery expenses, excluding non-cash compensation expense related to equity awards</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">89.2</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">83.5</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#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 colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">24.2</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">20.9</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#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 antisense drug discovery expenses</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">113.4</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">104.4</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#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;">Antisense drug discovery expenses were slightly higher in 2020 compared to 2019 due to expenses we incurred related to advancing our research programs and investments we made in complementary technologies to expand the reach of our antisense technology. All amounts exclude non-cash compensation expense related to equity awards.</div>
<div><br /></div>
<div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
<div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span>70</span></div>
</div>
<div style="page-break-after:always;"><hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>
<div></div>
</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;">Antisense 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 cellpadding="0" cellspacing="0" id="z03edf3248c804e01b88a039a5125b245" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <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;"></div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="6" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><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" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
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  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">TEGSEDI</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">14.7</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">16.8</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#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;">WAYLIVRA</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">5.6</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">7.4</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
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  <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;">IONIS-TTR-L<sub>Rx</sub></div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">34.0</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">14.1</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
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  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">IONIS-APOCIII-L<sub>Rx</sub></div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">5.6</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">7.6</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
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  <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 antisense development projects</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">86.9</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">86.6</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#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 colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">85.9</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">74.0</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#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 antisense drug development, excluding non-cash compensation expense related to equity awards</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">232.7</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">206.5</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
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  <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 colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">63.7</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">45.9</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#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 antisense drug development expenses</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">296.4</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">252.4</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
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<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our development expenses increased in 2020 compared to 2019 primarily due to our broad Phase 3 program for IONIS-TTR-L<sub>Rx</sub>, which we initiated in late 2019 and other medicines in our wholly-owned pipeline. These increases were slightly offset by decreases in expenses for TEGSEDI, WAYLIVRA, IONIS-FXI-L<sub>Rx</sub>, IONIS-APOCIII-L<sub>Rx</sub> and vupanorsen. We completed a Phase 2 study for IONIS-FXI-L<sub>Rx</sub> in 2019 and we completed Phase 2 studies for IONIS-APOCIII-L<sub>Rx</sub> and vupanorsen in early 2020. All amounts exclude non-cash compensation expense related to equity awards.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our antisense drug development expenses by segment were as follows (in millions):</div>
<div><br /></div>
<table cellpadding="0" cellspacing="0" id="z84d646ce10fb404b806670f219e7d627" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <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;"></div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="6" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><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" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2020</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2019</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#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;">Ionis Core</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">174.5</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">145.0</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#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;">Akcea Therapeutics</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">95.7</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">261.5</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#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;">Elimination of intercompany activity</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(37.5</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(200.0</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;"><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; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Subtotal</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">232.7</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">206.5</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#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 colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">63.7</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">45.9</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#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 antisense drug development expenses</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">296.4</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">252.4</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#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 may conduct multiple clinical trials on a drug candidate, including multiple clinical trials for the various indications we may be studying. Furthermore, as we obtain results from trials, we may elect to discontinue clinical trials for certain drug candidates in certain indications in order to focus our resources on more promising drug candidates or indications. Our Phase 1 and Phase 2 programs are clinical research programs that fuel our Phase 3 pipeline. When our medicines are in Phase 1 or Phase 2 clinical trials, they are in a dynamic state in which we may adjust the development strategy for each medicine. Although we may characterize a medicine as &#8220;in Phase 1&#8221; or &#8220;in Phase 2,&#8221; it does not mean that we are conducting a single, well-defined study with dedicated resources. Instead, we allocate our internal resources on a shared basis across numerous medicines based on each medicine&#8217;s particular needs at that time. This means we are constantly shifting resources among medicines. Therefore, what we spend on each medicine during a particular period is usually a function of what is required to keep the medicines progressing in clinical development, not what medicines we think are most important. For example, the number of people required to start a new study is large, the number of people required to keep a study going is modest and the number of people required to finish a study is large. However, such fluctuations are not indicative of a shift in our emphasis from one medicine to another and cannot be used to accurately predict future costs for each medicine. And, because we always have numerous medicines in preclinical and early stage clinical research, the fluctuations in expenses from medicine to medicine, in large part, offset one another. If we partner a medicine, it may affect the size of a trial, its timing, its total cost and the timing of the related costs.</div>
<div><br /></div>
<div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
<div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span>71</span></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="text-decoration: underline;">Manufacturing and Development Chemistry</span></div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Expenditures in our manufacturing and development chemistry function consist primarily of personnel costs, specialized chemicals for oligonucleotide manufacturing, laboratory supplies and outside services. Our manufacturing and development chemistry function is responsible for providing drug supplies to antisense drug development and our collaboration partners. Our manufacturing procedures include testing to satisfy good laboratory and good manufacturing practice requirements.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our manufacturing and development chemistry expenses were as follows (in millions):</div>
<div><br /></div>
<table cellpadding="0" cellspacing="0" id="zb28af96dbe4d44ec90bf92482d1394e5" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <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;"></div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="6" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><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" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2020</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2019</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#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 colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">55.9</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">42.5</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#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 colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.9</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">9.6</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#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 colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">66.8</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">52.1</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#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 increased in 2020 compared to 2019. The increase in manufacturing and development chemistry expenses was primarily related to manufacturing API for IONIS-TTR-L</span><sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> and IONIS-APOCIII-L</span><sub>Rx </sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">for our Phase 3 studies. All amounts exclude non-cash compensation expense related to equity awards.</span></div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our manufacturing and development chemistry expenses by segment were as follows (in millions):</div>
<div><br /></div>
<table cellpadding="0" cellspacing="0" id="z67b6c6bee0d14f4888d92c0523c7386a" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <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;"></div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="6" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><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" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2020</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2019</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#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;">Ionis Core</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">42.6</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">36.8</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#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;">Akcea Therapeutics</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">18.6</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">11.2</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#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;">Elimination of intercompany activity</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(5.3</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(5.5</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;"><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; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Subtotal</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">55.9</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">42.5</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#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 colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.9</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">9.6</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#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 manufacturing and development chemistry expenses</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">66.8</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">52.1</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#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="text-decoration: underline;">R&amp;D Support</span></div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In our research, development and patent expenses, we include support costs such as rent, repair and maintenance for buildings and equipment, utilities, depreciation of laboratory equipment and facilities, amortization of our intellectual property, informatics costs, procurement costs and waste disposal costs. We call these costs R&amp;D support expenses.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following table sets forth information on R&amp;D support expenses (in millions):</div>
<div><br /></div>
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  <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;"></div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="6" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><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" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
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  <tr>
    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2020</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2019</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#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 colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">14.7</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">15.2</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#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 colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.2</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">9.4</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Patent expenses</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4.1</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4.2</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Insurance</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2.4</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1.8</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Computer software and licenses</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2.9</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1.1</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 2px;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Other</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">7.4</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6.1</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#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 R&amp;D support expenses, excluding non-cash compensation expense related to equity awards</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">41.7</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">37.8</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#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 colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">16.8</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">19.0</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#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 R&amp;D support expenses</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">58.5</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">56.8</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
</table>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">R&amp;D support expenses for 2020 increased compared to 2019 primarily due to costs from growth in our operations. All amounts exclude non-cash compensation expense related to equity awards.</div>
<div><br /></div>
<div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
<div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span>72</span></div>
</div>
<div style="page-break-after:always;"><hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>
<div></div>
</div>
<div><br /></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our R&amp;D support expenses by segment were as follows (in millions):</div>
<div><br /></div>
<table cellpadding="0" cellspacing="0" id="zb57aeb47ab524a3eb0085d270d22106e" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <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;"></div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="6" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><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" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2020</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2019</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#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;">Ionis Core</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">19.2</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">29.7</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#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;">Akcea Therapeutics</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">22.7</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">8.3</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#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;">Elimination of intercompany activity</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(0.2</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(0.2</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;"><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; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Subtotal</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">41.7</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">37.8</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#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 colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">16.8</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">19.0</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#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 colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">58.5</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">56.8</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>
  </tr>
</table>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Selling, General and Administrative Expenses</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Selling, general and administrative, or SG&amp;A, expenses include personnel and outside costs associated with the pre-commercialization and commercialization activities for our medicines and costs to support our company, our employees and our stockholders including, legal, human resources, investor relations, and finance. Additionally, we include in selling, general and administrative expenses such costs as rent, repair and maintenance of buildings and equipment, depreciation and utilities costs that we need to support the corporate functions listed above. We also include fees we owe under our in-licensing agreements related to SPINRAZA.</div>
<div><br /></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following table sets forth information on SG&amp;A expenses (in millions):</div>
<div><br /></div>
<table cellpadding="0" cellspacing="0" id="z485726d9f5f0460288df1cf62905e802" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <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;"></div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="6" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><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" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2020</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2019</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#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 colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">241.8</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">235.8</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#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 colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">112.5</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">50.8</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#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 colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">354.3</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">286.6</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#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 <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">were slightly higher for </span>2020<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> compared to </span>2019 principally due to costs related to the Akcea Acquisition, including severance and retention costs and legal costs related to the Alnylam arbitration. These increases were mostly offset by reductions in travel and marketing events as a result of the COVID-19 pandemic<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. All amounts exclude non-cash compensation expense related to equity awards.</span></div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our SG&amp;A expenses by segment were as follows (in millions):</div>
<div><br /></div>
<table cellpadding="0" cellspacing="0" id="z1442f29d3ecf48f2aa30fe5f3341c84c" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <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;"></div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="6" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><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" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2020</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2019</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#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;">Ionis Core</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">86.8</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">78.9</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#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;">Akcea Therapeutics</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">155.0</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">156.9</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#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;">Subtotal</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">241.8</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">235.8</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#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 colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">112.5</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">50.8</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#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 colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">354.3</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">286.6</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
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</table>
<div><br /></div>
<div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
<div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span>73</span></div>
</div>
<div style="page-break-after:always;"><hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>
<div></div>
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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; font-weight: bold;">Akcea Therapeutics, Inc.</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) for our Akcea Therapeutics business segment:</div>
<div><br /></div>
<table cellpadding="0" cellspacing="0" id="z86dd8423b5f24ecb89642e576e6784ca" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <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;"></div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="6" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><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" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
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  <tr>
    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2020</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2019</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
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  <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 products sold</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">18.9</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">12.8</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#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;">Development and patent expenses</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">99.6</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">81.0</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#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;">Sublicense fees to Ionis</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">37.5</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">200.0</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#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;">Selling, general and administrative expenses</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">155.0</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">156.9</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#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;">Profit (loss) share for TEGSEDI commercialization activities</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(16.2</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(37.3</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;"><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; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total operating expenses, excluding non-cash compensation expense related to equity awards</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">294.8</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">413.4</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#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 colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">94.8</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">37.1</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#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 Akcea Therapeutics operating expenses</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">389.6</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">450.5</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#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;">See discussion of fluctuations of Akcea operating expenses in the operating expense sections above. All amounts exclude non-cash compensation expense related to equity awards.</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 2020 was $30.6 million compared to $52.0 million for 2019. The decrease in investment income was primarily due to a decrease in interest rates during 2020 compared to 2019.</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 cellpadding="0" cellspacing="0" id="zd42203fdf78144a398b1a7c1d7f9cae9" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <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;"></div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="6" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><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" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2020</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2019</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#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 colspan="1" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;"><div style="text-align: left; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Non-cash amortization of the debt discounts and debt issuance costs</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">38.7</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">39.3</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#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 colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3.8</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6.7</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#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;">Interest on mortgage for primary R&amp;D and manufacturing facilities</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2.4</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2.4</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#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;">Other</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.1</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.4</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#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 interest expense</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">45.0</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">48.8</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#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 interest expense payable in cash decreased in 2020 compared 2019 because we exchanged a significant portion of our 1% Notes for 0.125% Notes in December 2019.</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 Investments</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Gain on investments for 2020 was $16.5 million compared to $0.2 million for 2019. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">During the second and fourth quarters of 2020, we revalued our investments in three privately held companies, Dynacure, Suzhou-Ribo and Aro Biotherapeutics because the companies sold additional equity securities that were similar to the equity we own. Because of these observable price changes we recognized a $6.3 million gain on our investment in Dynacure, a $3.0 million gain on our investment in Suzhou-Ribo and a $5.5 million gain on our investment in Aro Biotherapeutics in our consolidated statement of operations during 2020 because the sales were at higher prices compared to our recorded value.</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;">Early Retirement of Debt</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">As a result of the debt exchange we completed in December 2019, we recorded a $21.9 million non-cash loss on early retirement of debt, reflecting the early retirement of a portion of our 1% Notes. The non-cash loss on the early retirement of our debt is the difference between the amount paid to exchange our 1% Notes that we attributed to the liability component and the net carrying balance of the liability component at the time that we completed the debt exchange.</div>
<div><br /></div>
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<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span>74</span></div>
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<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">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 had income tax expense of $316.7 million for 2020 compared to an income tax expense of $43.5 million for 2019<span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;">. </span>Our 2020 income tax expense primarily relates to a non-cash tax expense of $313 million related to an increase<span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;">&#xA0;</span>in the valuation allowance recorded against Ionis&#8217; U.S. federal net deferred tax assets in the fourth quarter of 2020. We now maintain a valuation allowance against all our consolidated U.S. federal and state net deferred tax assets. See discussion of our valuation allowance under the section titled, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Income Taxes</span>, above in our discussion of our critical accounting estimates.</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 Income (Loss)</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 $486.8 million for 2020 compared to net income of $303.3 million for 2019. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Our net loss for 2020 was primarily due to the valuation allowance we recorded as a result of the Akcea Acquisition, as discussed above in the income tax expense section. Also contributing to our net loss in 2020 was decreased revenue year-over-year, as discussed above in the revenue section and an increase in operating expenses year-over-year, as discussed above in the operating expense section.</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;">Net Income (Loss) Attributable to Noncontrolling Interest in Akcea Therapeutics, Inc.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our noncontrolling interest in Akcea on our statement of operations for 2020 was a net loss of $35.5 million compared to net income of $9.1 million for 2019.<span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;">&#xA0;</span>The net loss attributable to noncontrolling interest in Akcea for the year ended December 31, 2020, represents the portion of Akcea&#8217;s net loss that third parties owned for the period from January 1, 2020 until we acquired 100 percent of Akcea in October 2020. After our acquisition of Akcea in October 2020, we no longer recorded any adjustment related to noncontrolling interest for Akcea&#8217;s net loss. Akcea generated net income in 2019 primarily because it earned significant license fee revenue from Novartis and Pfizer.</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 Income (Loss) Attributable to Ionis Pharmaceuticals, Inc. Common Stockholders<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> and Net Income (Loss) per Share</span></div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We had a net loss attributable to our common stockholders of $451.3 million for 2020 compared to net income of $294.1 million in 2019. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Basic and diluted net loss per share for </span>2020<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> were each $</span>3.23<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. Basic and diluted net income per share for 2019 was $</span>2.12<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> and $</span>2.08<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, respectively.</span></div>
<div><br /></div>
<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Liquidity and Capital Resources</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We have financed our operations primarily from research and development collaborative agreements. </span>We also finance our operations from commercial revenue from SPINRAZA royalties and product sales. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">From our inception through December 31, </span>2020, we have earned approximately $5.0 billion<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> in revenue. We have also financed our operations through the sale of our equity securities and the issuance of long-term debt. From the time we were founded through December 31, </span>2020<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, we have raised net proceeds of approximately $</span>2.0&#xA0;<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">billion from the sale of our equity securities. Additionally, we borrowed approximately $</span>1.5<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> billion under long-term debt arrangements to finance a portion of our operations over the same time period.</span></div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Our key liquidity metrics and capital resources include our cash, cash equivalents and short-term investments, working capital and debt obligations. During 2020 we used a portion of our cash to complete the Akcea Acquisition. At December 31, 2020, we had $1.9 billion of cash and short-term investments on hand. We believe our cash and short-term investment balance is sufficient to fund our operations both in the short-</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">term (i.e., the next 12 months) and in the long-term (i.e., beyond the next 12 months)</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. </span>In 2020 our working capital decreased because our cash and investments decreased and our 1% Notes became a current liability.</div>
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<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span>75</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 following table summarizes our contractual obligations as of December 31, 2020. The table provides a breakdown of when obligations become due. We provide a more detailed description of the major components of our debt in the paragraphs following the table:</div>
<div><br /></div>
<table cellpadding="0" cellspacing="0" id="zd8ba2ea7ed4241768a4e64f8dafc52d3" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <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 colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="10" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><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 colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#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 colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Total</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><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 colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><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 colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#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% Notes (principal and interest payable)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">313.0</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">313.0</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 64%;"><div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.125% Notes (principal and interest payable)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">551.6</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.7</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">550.9</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Building mortgage payments</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">75.8</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2.4</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">73.4</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#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;">Other obligations (principal and interest payable)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.9</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.1</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.8</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Operating leases</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">23.3</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3.3</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">20.0</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 64%; padding-bottom: 4px;"><div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">964.6</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">319.5</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">645.1</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#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 facility mortgages, facility leases, equipment financing arrangements and other obligations. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Due to the uncertainty with respect to the timing of future cash outflows associated with our unrecognized tax benefits, we are unable to make reasonably reliable estimates of the period of cash settlement with the respective taxing authorities. Therefore, we have excluded our gross unrecognized tax benefits from our contractual obligations table above. We have not entered into, nor do we currently have, any off-balance sheet arrangements (as defined under SEC rules).</span></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;">0.125 Percent Convertible Senior Notes 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;">In December 2019, we entered into privately negotiated exchange and/or subscription agreements with certain new investors and certain holders of our existing 1% Notes to exchange $375.6 million of our 1% Notes for $439.3 million of our 0.125% Notes, and to issue $109.5 million of our 0.125% Notes. We completed this exchange to reduce our cash interest payments, increase our conversion price and extend our maturity for a large portion of our debt. Additionally, i</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">n conjunction with the December 2019 exchange, 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 conversion price on our 0.125% Notes even further<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. </span>We accounted for our call spread transactions using the Derivatives and Hedging &#8211; Contracts in Entity&#8217;s Own Equity accounting guidance contained in Topic 815. We determined that the call spread transactions meet the definition of a derivative, are indexed to our stock and meet the criteria to be classified in shareholders&#8217; equity.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The call spread cost us $52.6 million of which $108.7 million was for the note hedge purchase offset by $56.1 million we received for selling the warrants. We increased our effective conversion price to $123.38 with the same number of underlying shares as our 0.125% Notes.</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;">Similar to our </span>0.125% Notes<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, our note hedges are subject to adjustment. Additionally, our note hedges are exercisable upon conversion of the </span>0.125% Notes<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. The note hedges will expire upon maturity of the </span>0.125% Notes<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, or December 2024. The note hedges and warrants are separate transactions and are not part of the terms of our </span>0.125% Notes<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. The holders of the </span>0.125% Notes<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> do not have any rights with respect to the note hedges and warrants.</span></div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We recorded the aggregate amount paid for the note hedges and the aggregate amount received for the warrants in additional paid-in capital in our consolidated balance sheet. See our Call Spread accounting policy in Note 1, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Organization and Significant Accounting Policies</span>, in the Notes to the Consolidated Financial Statements. We reassess our ability to continue to classify the note hedges and warrants in shareholders&#8217; equity at each reporting period. We excluded shares under the note hedges from our calculation of diluted earnings per share as they were antidilutive. We will include the shares issuable under the 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: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">At December 31, 2020, we had the following 0.125% Notes outstanding (amounts in millions except price per share data):</div>
<div><br /></div>
<table cellpadding="0" cellspacing="0" id="z14074044da264b85a429f3e1b65f93a5" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td valign="bottom" style="vertical-align: top; padding-bottom: 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"></div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: top; border-bottom: #000000 solid 2px;"><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" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#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 colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">548.8</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: top;"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Maturity date</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: top;"><div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">December 2024</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#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;">Interest rate</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: top; background-color: #CCEEFF;"><div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.125 percent</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: top; width: 88%;"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Conversion price per share</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">83.28</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#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 colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6.6</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
</table>
<div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
<div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span>76</span></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;">Interest is payable semi-annually for the 0.125% Notes. The 0.125% Notes are convertible under certain conditions, at the option of the note holders. We can settle conversions of the 0.125% Notes, at our election, in cash, shares of our common stock or a combination of both. We may not redeem the 0.125% Notes prior to maturity, and no sinking fund is provided for them. Holders of the 0.125% Notes may require us to purchase some or all of their notes upon the occurrence of certain fundamental changes, as set forth in the indenture governing the 0.125% Notes, at a purchase price equal to 100 percent of the principal amount of the notes to be purchased, plus accrued and unpaid interest.</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;">1 Percent Convertible Senior Notes</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 November 2014, we completed a $500 million offering of convertible senior notes, which mature in 2021 and bear interest at 1 percent. </span>In December 2016, we issued an additional $185.5 million of 1% Notes in exchange for the redemption of a portion of our previously outstanding 2&#190;% Notes. In December 2019, we exchanged a portion of our 1% Notes for new 0.125% Notes.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">At December 31, 2020, we had the following 1% Notes outstanding (amounts in millions except price per share data):</div>
<div><br /></div>
<table cellpadding="0" cellspacing="0" id="z0b86bbe1fdd04254abe167aaa7c36a2d" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td valign="bottom" style="vertical-align: top; padding-bottom: 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"></div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: top; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">1% Notes</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: top; width: 88%; background-color: #CCEEFF;"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Outstanding principal balance</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">309.9</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: top;"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Maturity date</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: top;"><div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">November 2021</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#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;">Interest rate</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: top; background-color: #CCEEFF;"><div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1 percent</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: top; width: 88%;"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Conversion price per share</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">66.81</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#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 colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4.6</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#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;">Interest is payable semi-annually for the 1% Notes. The 1% Notes are convertible under certain conditions, at the option of the note holders. We settle conversions of the 1% Notes, at our election, in cash, shares of our common stock or a combination of both. We may not redeem the 1% Notes prior to maturity, and no sinking fund is provided for them. Holders of the 1% Notes may require us to purchase some or all of their notes upon the occurrence of certain fundamental changes, as set forth in the indenture governing the 1% Notes, at a purchase price equal to 100 percent of the principal amount of the notes to be purchased, plus accrued and unpaid interest.</div>
<div><br /></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Research and Development and Manufacturing Facilities</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In July 2017, we purchased the building that houses our primary R&amp;D facility for $79.4 million and our manufacturing facility for $14.0 million. We financed the purchase of these two facilities with mortgage debt of $60.4 million in total. Our primary R&amp;D facility mortgage has 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 are only required to make interest payments. Both mortgages mature in August 2027.</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, 2020 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, or securing lines of credit. Whether we use our existing capital resources or choose to obtain financing will depend on various factors, including the future success of our business, the prevailing interest rate environment and the condition of financial markets generally.</div>
<div><br /></div>
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">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 are 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</span>.</div>
<div><br /></div>
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<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span>77</span></div>
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<div><br /></div>
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">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;">Item 9. Changes in and Disagreements with Accountants on Accounting and Financial Disclosure</div>
<div><br /></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">None.</div>
<div><br /></div>
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">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 evaluate 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, 2020.</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, 2020, 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, 2020.</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, 2020, as stated in their attestation report, which is included elsewhere herein.</div>
<div><br /></div>
<div style="text-align: left; text-indent: -18pt; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Changes in Internal Control over Financial Reporting</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The above assessment did not identify any change in our internal control over financial reporting that occurred during our latest fiscal quarter and that has materially affected, or is reasonably likely to materially affect, our internal control over financial reporting.</div>
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<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span>78</span></div>
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<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">REPORT OF INDEPENDENT REGISTERED PUBLIC ACCOUNTING FIRM</div>
<div><br /></div>
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">To the Stockholders and Board of Directors of Ionis Pharmaceuticals, Inc.</div>
<div><br /></div>
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Opinion on Internal Control over Financial Reporting</div>
<div 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, 2020, 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, 2020, 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, 2020 and 2019, and the related consolidated statements of operations, comprehensive income (loss), stockholders&#8217; equity, and cash flows for each of the three years in the period ended December 31, 2020, and the related notes and our report dated February 24, 2021 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 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 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 24, 2021</div>
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<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span>79</span></div>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Item 9B. Other Information</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Not applicable.</div>
<div><br /></div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">PART III</div>
<div><br /></div>
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">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, 2020<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 incorporate by reference the required information concerning our Code of Ethics from the information under the caption &#8220;Code of Ethics and Business Conduct&#8221; contained in the Proxy Statement. Our Code of Ethics and Business Conduct is posted on our website at www.ionispharma.com<sup>(1)</sup>. We intend to disclose future amendments to, or waivers from, our Code of Ethics and Business Conduct on our website.</div>
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">________________</div>
<div>
<table 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="z47b74a409ebd43a6819f38449ba65462">
  <tr>
    <td style="width: 18pt; vertical-align: top; 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; text-indent: 18pt; 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;">Item 11. Executive Compensation</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We incorporate by reference the information required by this item to the information under the caption &#8220;EXECUTIVE COMPENSATION,&#8221; &#8220;Compensation Committee Interlocks and Insider Participation&#8221; and &#8220;COMPENSATION COMMITTEE REPORT&#8221; contained in the Proxy Statement.</div>
<div><br /></div>
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">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, 2020.</div>
<div style="text-align: left;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> </span><br /></div>
<table cellpadding="0" cellspacing="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" id="z1d00327619be4bb88471ff5f107c8bc2">
  <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 colspan="2" style="width: 17.48%; 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;">Weighted Average</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Exercise Price of</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Outstanding Options</div></td>
    <td style="width: 0.87%; vertical-align: bottom;">&#160;</td>
    <td style="width: 16.36%; vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Number of Shares</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Remaining Available</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">for Future Issuance</div></td>
    <td style="width: 2.24%; vertical-align: bottom;">&#160;</td>
  </tr>
  <tr>
    <td style="width: 41.45%; vertical-align: bottom; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Equity compensation plans approved by stockholders (a)</div></td>
    <td style="width: 1%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 19.85%; vertical-align: bottom; border-bottom: #000000 2px solid; background-color: #CCEEFF;"><div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">12,394,777</div></td>
    <td style="width: 0.75%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 2.87%; vertical-align: bottom; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td style="width: 14.61%; vertical-align: bottom; background-color: #CCEEFF;"><div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">54.11</div></td>
    <td style="width: 0.87%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 16.36%; vertical-align: bottom; border-bottom: #000000 2px solid; background-color: #CCEEFF;"><div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">8,325,343</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;">12,394,777</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;">54.11</div></td>
    <td style="width: 0.87%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 16.36%; vertical-align: bottom; border-bottom: #000000 4px double; background-color: #FFFFFF;"><div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">8,325,343</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 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="z38ae9ebe702f49d78fe4700eb2180295">
  <tr>
    <td style="width: 36pt; vertical-align: top; align: right; 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 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="z8d64af8f4e5d43169f11bac9cbd2794b">
  <tr>
    <td style="width: 36pt; vertical-align: top; align: right; 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, 662,511 remained available for purchase under the ESPP as of December 31, 2020.</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, see Note 4, <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="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
<div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span>80</span></div>
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</div>
<div><br /></div>
<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Item 13. Certain Relationships and Related Transactions, and Director Independence</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We incorporate by reference the information required by this item to the information under the captions &#8220;Independence of the Board of Directors&#8221; and &#8220;Certain Relationships and Related Transactions&#8221; contained in the Proxy Statement.</div>
<div><br /></div>
<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Item 14. Principal Accounting 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;">PART IV</div>
<div style="text-align: center;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> </span><br /></div>
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Item 15. Exhibits, Financial Statement Schedules</div>
<div style="text-align: left;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> </span><br /></div>
<div style="text-align: left; text-indent: -36pt; margin-left: 72pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(a)(1) Index to Financial Statements</div>
<div style="text-align: justify; text-indent: -36pt; margin-left: 72pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> </span><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We submitted the consolidated financial statements required by this item in a separate section beginning on page F-1 of this Report.</div>
<div style="text-align: left; text-indent: 36pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> </span><br /></div>
<div style="text-align: left; text-indent: -36pt; margin-left: 72pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(a)(2) Index to Financial Statement Schedules</div>
<div style="text-align: left; text-indent: -36pt; margin-left: 72pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> </span><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We omitted these schedules because they are not required, or are not applicable, or the required information is shown in the consolidated financial statements or notes thereto.</div>
<div style="text-align: left; text-indent: 36pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> </span><br /></div>
<div style="text-align: left; text-indent: -36pt; margin-left: 72pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(a)(3) Index to Exhibits</div>
<div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
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<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span>81</span></div>
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<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">INDEX TO EXHIBITS</div>
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<table cellpadding="0" cellspacing="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" id="z6406f2b5e3b1484ab9ae08858a8ea029">
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    <td style="width: 7.41%; vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Exhibit Number</div></td>
    <td style="width: 2.17%; vertical-align: bottom;">&#160;</td>
    <td style="width: 90.43%; 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>
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    <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: 2.17%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 90.43%; 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/874015/000119312520235408/d75253dex21.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">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>
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    <td style="width: 7.41%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 2.17%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 90.43%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
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    <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;">3.1</div></td>
    <td style="width: 2.17%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 90.43%; 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/874015/000087401518000047/exhibit3_1.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">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>
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    <td style="width: 7.41%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 2.17%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 90.43%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
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    <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: 2.17%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 90.43%; 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/874015/000114036114017588/formdef14a.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Certificate of Amendment to Restated Certificate of Incorporation</a><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;">, </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">filed June 17, 2014. - Filed as an exhibit to the Registrant&#8217;s Notice of Annual Meeting and Proxy Statement, for the 2014 Annual Meeting of Stockholders, filed with the SEC on April 25, 2014 and incorporated herein by reference.</span></div></td>
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    <td style="width: 7.41%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 2.17%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 90.43%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
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    <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;">3.3</div></td>
    <td style="width: 2.17%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 90.43%; 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/874015/000114036115045083/ex3_1.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Certificate of Amendment to Restated Certificate of Incorporation</a><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;">, </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">filed December 18, 2015. - 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>
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    <td style="width: 7.41%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 2.17%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 90.43%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
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    <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: 2.17%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 90.43%; 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/874015/000114036115045083/ex3_2.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">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 December 18, 2015 and incorporated herein by reference.</span></div></td>
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    <td style="width: 7.41%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 2.17%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 90.43%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
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    <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;">4.1</div></td>
    <td style="width: 2.17%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 90.43%; 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/874015/000091205700053343/a2032851zex-4_2.txt" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">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 Report on Form 8-K filed December 13, 2000 and incorporated herein by reference.</span></div></td>
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    <td style="width: 7.41%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 2.17%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 90.43%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
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    <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: 2.17%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 90.43%; 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/874015/000087401518000047/exhibit4_2.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">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>
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    <td style="width: 7.41%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 2.17%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 90.43%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
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    <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;">4.3</div></td>
    <td style="width: 2.17%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 90.43%; 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/874015/000110465914082750/a14-24885_1ex4d1.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Indenture, dated as of November 17, 2014, between the Registrant and Wells Fargo Bank, National Association, as trustee, including Form of 1.00 percent Convertible Senior Note due 2021</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 November 21, 2014 and incorporated herein by reference.</span></div></td>
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    <td style="width: 7.41%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 2.17%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 90.43%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
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    <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: 2.17%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 90.43%; 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/874015/000114036119023019/ex4_1.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Indenture, dated as of December 19, 2019, by and between Ionis Pharmaceuticals, Inc. 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>
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    <td style="width: 7.41%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 2.17%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 90.43%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
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    <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;">4.5</div></td>
    <td style="width: 2.17%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 90.43%; 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/874015/000114036119022393/ex99_1.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Form of Exchange and/or Subscription Agreement for Ionis Pharmaceuticals, Inc. 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>
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    <td style="width: 7.41%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 2.17%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 90.43%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
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    <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: 2.17%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 90.43%; 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/874015/000114036119022393/ex99_2.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Form of Convertible Note Hedge Transactions Confirmation</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>
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    <td style="width: 7.41%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 2.17%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 90.43%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
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    <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;">4.7</div></td>
    <td style="width: 2.17%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 90.43%; 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/874015/000114036119022393/ex99_3.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Form of Warrant Transactions Confirmation</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>
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    <td style="width: 7.41%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 2.17%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 90.43%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
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    <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: 2.17%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 90.43%; 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/874015/000114036120004500/exhibit4_9.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">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, 2019 and incorporated herein by reference.</span></div></td>
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    <td style="width: 7.41%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 2.17%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 90.43%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
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    <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: 2.17%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 90.43%; 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/874015/000110465913016208/a12-28450_1ex10d1.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Form of Indemnity Agreement entered into between the Registrant and its Directors and Officers with related schedule</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.</span></div></td>
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    <td style="width: 7.41%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 2.17%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 90.43%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
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    <td style="width: 7.41%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.2*</div></td>
    <td style="width: 2.17%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 90.43%; 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/874015/000110465912025639/a12-1729_1def14a.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Registrant&#8217;s 1989 Stock Option Plan, as amended</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed as an exhibit to Registrant&#8217;s Notice of Annual Meeting and Proxy Statement for the 2012 Annual Meeting of Stockholders, filed with the SEC on April 16, 2012 and incorporated herein by reference.</span></div></td>
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    <td style="width: 2.17%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 90.43%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
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    <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;">10.3*</div></td>
    <td style="width: 2.17%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 90.43%; 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/874015/000114036119005627/ex10_2.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">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 with the SEC on March 26, 2019 and incorporated herein by reference.</span></div></td>
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<table cellpadding="0" cellspacing="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" id="zbe1f6a20117f4b95b4eb03f9feabe7ad">
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    <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;">10.4</div></td>
    <td style="width: 2.07%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>
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  </tr>
  <tr>
    <td style="width: 7.5%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 2.07%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
    <td colspan="2" style="width: 90.43%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
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  <tr>
    <td style="width: 7.5%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.5</div></td>
    <td style="width: 2.07%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>
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  <tr>
    <td style="width: 7.5%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 2.07%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
    <td colspan="2" style="width: 90.43%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
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  <tr>
    <td style="width: 7.5%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.6</div></td>
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  </tr>
  <tr>
    <td style="width: 7.5%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 2.07%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
    <td colspan="2" style="width: 90.43%; vertical-align: top; background-color: #FFFFFF;">&#160;</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;">10.7</div></td>
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  <tr>
    <td style="width: 7.5%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 2.07%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
    <td colspan="2" style="width: 90.43%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
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    <td style="width: 2.07%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>
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  </tr>
  <tr>
    <td style="width: 7.5%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 2.07%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
    <td colspan="2" style="width: 90.43%; vertical-align: top; background-color: #FFFFFF;">&#160;</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;">10.9</div></td>
    <td style="width: 2.07%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>
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    <td style="width: 7.5%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 2.07%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
    <td colspan="2" style="width: 90.43%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
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  <tr>
    <td style="width: 7.5%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.10</div></td>
    <td style="width: 2.07%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>
    <td colspan="2" style="width: 90.43%; 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/874015/000087401517000033/ex10_3.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Amendment #1 between the Registrant and Bayer AG dated February 10, 2017</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, 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: 7.5%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 2.07%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
    <td colspan="2" style="width: 90.43%; vertical-align: top; background-color: #FFFFFF;">&#160;</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;">10.11</div></td>
    <td style="width: 2.07%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>
    <td colspan="2" style="width: 90.43%; 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/874015/000110465913081234/a13-19600_1ex10d4.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Registrant&#8217;s Amended and Restated 10b5-1 Trading Plan dated September 12, 2013</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed as an exhibit to the Registrant&#8217;s Quarterly Report on Form 10-Q for the quarter ended September 30, 2013 and incorporated herein by reference.</span></div></td>
  </tr>
  <tr>
    <td style="width: 7.5%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 2.07%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
    <td colspan="2" style="width: 90.43%; vertical-align: top; background-color: #FFFFFF;">&#160;</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: 2.07%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>
    <td colspan="2" style="width: 90.43%; 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/874015/000114036114017588/formdef14a.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Registrant&#8217;s Amended and Restated 2002 Non-Employee Directors&#8217; Stock Option Plan, as amended</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed as an exhibit to the Registrant&#8217;s Notice of Annual Meeting and Proxy Statement for the 2020 Annual Meeting of Stockholders, filed with the SEC on April 24, 2020 and incorporated herein by reference.</span></div></td>
  </tr>
  <tr>
    <td style="width: 7.5%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 2.07%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
    <td colspan="2" style="width: 90.43%; vertical-align: top; background-color: #FFFFFF;">&#160;</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;">10.13*</div></td>
    <td colspan="2" 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 href="https://www.sec.gov/Archives/edgar/data/874015/000110465912054509/a12-13652_1ex10d3.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Form of Restricted Stock Unit Agreement for Restricted Stock Units granted under the Ionis Pharmaceuticals, Inc. Amended and Restated 2002 Non-Employee Directors&#8217; Stock Option Plan</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed as an exhibit to the Registrant&#8217;s Form S-8 filed on August 7, 2020 and incorporated herein by reference.</span></div></td>
  </tr>
  <tr>
    <td style="width: 7.5%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td colspan="2" style="width: 2.23%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 90.27%; vertical-align: top; background-color: #FFFFFF;">&#160;</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 colspan="2" 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 href="https://www.sec.gov/Archives/edgar/data/874015/000087401518000047/exhibit10_17.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">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: 7.5%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td colspan="2" style="width: 2.23%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 90.27%; vertical-align: top; background-color: #FFFFFF;">&#160;</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;">10.15*</div></td>
    <td colspan="2" 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 href="https://www.sec.gov/Archives/edgar/data/874015/000114036119007625/nc10001158x1_def14a.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">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 2019 Annual Meeting of Stockholders and Proxy Statement filed with the SEC on April 26, 2019 and incorporated herein by reference.</span></div></td>
  </tr>
  <tr>
    <td style="width: 7.5%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td colspan="2" style="width: 2.23%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 90.27%; vertical-align: top; background-color: #FFFFFF;">&#160;</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 colspan="2" 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 href="https://www.sec.gov/Archives/edgar/data/874015/000087401515000082/ex10_4.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">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 Quarterly Report on Form 10-Q for the quarter ended September 30, 2015 and incorporated herein by reference.</span></div></td>
  </tr>
  <tr>
    <td style="width: 7.5%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td colspan="2" style="width: 2.23%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 90.27%; vertical-align: top; background-color: #FFFFFF;">&#160;</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;">10.17*</div></td>
    <td colspan="2" 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 href="https://www.sec.gov/Archives/edgar/data/874015/000110465911044856/a11-23763_1ex99d3.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Form of Time-Vested Restricted Stock Unit Agreement for Restricted Stock Units granted under the 2011 Equity Incentive Plan</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 with the SEC on August 8, 2011 and incorporated herein by reference.</span></div></td>
  </tr>
  <tr>
    <td style="width: 7.5%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td colspan="2" style="width: 2.23%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 90.27%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
  </tr>
  <tr>
    <td style="width: 7.5%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="exhibit10_18.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.18</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">*</span></div></td>
    <td colspan="2" 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;">Forms of Performance Based Restricted Stock Unit Grant Notice and Performance Based Restricted Stock Unit Agreement for Performance Based Restricted Stock Units granted under the 2011 Equity Incentive Plan.</div></td>
  </tr>
</table>
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<table cellpadding="0" cellspacing="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" id="z604af5cd917b4cc6ad097fdc5a6950c9">
  <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;">10.19*</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 href="https://www.sec.gov/Archives/edgar/data/874015/000114036120030055/brhc10018560_ex99-1.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">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 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: #FFFFFF;">&#160;</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;">&#160;</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;">&#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 href="https://www.sec.gov/Archives/edgar/data/874015/000114036120030055/brhc10018560_ex99-2.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">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 </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Registrant&#8217;s 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: #FFFFFF;">&#160;</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;">&#160;</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;">10.21*</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 href="https://www.sec.gov/Archives/edgar/data/874015/000114036120030055/brhc10018560_ex99-3.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">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 </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Registrant&#8217;s 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: #FFFFFF;">&#160;</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;">&#160;</td>
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    <td style="width: 90.27%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
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  <tr>
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    <td style="width: 2.23%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
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  <tr>
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    <td style="width: 2.23%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 90.27%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
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  <tr>
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    <td style="width: 7.5%; vertical-align: top; background-color: #FFFFFF;">&#160;</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;">&#160;</td>
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    <td style="width: 2.23%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 90.27%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
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  <tr>
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    <td style="width: 7.5%; vertical-align: top; background-color: #FFFFFF;">&#160;</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;">&#160;</td>
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  <tr>
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    <td style="width: 7.5%; vertical-align: top; background-color: #FFFFFF;">&#160;</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;">&#160;</td>
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  <tr>
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    <td style="width: 2.23%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>
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    <td style="width: 7.5%; vertical-align: top; background-color: #FFFFFF;">&#160;</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;">&#160;</td>
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  <tr>
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    <td style="width: 2.23%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>
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  <tr>
    <td style="width: 7.5%; vertical-align: top; background-color: #FFFFFF;">&#160;</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;">&#160;</td>
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    <td style="width: 2.23%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>
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  <tr>
    <td style="width: 7.5%; vertical-align: top; background-color: #FFFFFF;">&#160;</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;">&#160;</td>
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  <tr>
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    <td style="width: 7.5%; vertical-align: top; background-color: #FFFFFF;">&#160;</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;">&#160;</td>
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<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span>84</span></div>
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<table cellpadding="0" cellspacing="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" id="zd15f5e5b32644e218963b349a744e296">
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    <td style="width: 1.6%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>
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    <td style="width: 7.64%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 1.6%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 90.76%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
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  <tr>
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  <tr>
    <td style="width: 7.64%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 1.6%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 90.76%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
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    <td style="width: 7.64%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 1.6%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 90.76%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
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  <tr>
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  <tr>
    <td style="width: 7.64%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 1.6%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 90.76%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
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  <tr>
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    <td style="width: 1.6%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>
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    <td style="width: 7.64%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 1.6%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 90.76%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
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  <tr>
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  </tr>
  <tr>
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  <tr>
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  <tr>
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    <td style="width: 90.76%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
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  <tr>
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  <tr>
    <td style="width: 7.64%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 1.6%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 90.76%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
  </tr>
  <tr>
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  </tr>
  <tr>
    <td style="width: 7.64%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 1.6%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 90.76%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
  </tr>
  <tr>
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  </tr>
  <tr>
    <td style="width: 7.64%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 1.6%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 90.76%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
  </tr>
  <tr>
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  <tr>
    <td style="width: 7.64%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 1.6%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 90.76%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
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  <tr>
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<div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span>85</span></div>
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<table cellpadding="0" cellspacing="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" id="z4930353665e546d687c86f7d38383d41">
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  <tr>
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    <td style="width: 1.6%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 90.76%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
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  <tr>
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    <td style="width: 1.6%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>
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  </tr>
  <tr>
    <td style="width: 7.64%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 1.6%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 90.76%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
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  <tr>
    <td style="width: 7.64%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.48</div></td>
    <td style="width: 1.6%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>
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  <tr>
    <td style="width: 7.64%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 1.6%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 90.76%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
  </tr>
  <tr>
    <td style="width: 7.64%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.49</div></td>
    <td style="width: 1.6%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>
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  </tr>
  <tr>
    <td style="width: 7.64%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 1.6%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 90.76%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
  </tr>
  <tr>
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    <td style="width: 1.6%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>
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  </tr>
  <tr>
    <td style="width: 7.64%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 1.6%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 90.76%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
  </tr>
  <tr>
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    <td style="width: 1.6%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>
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  </tr>
  <tr>
    <td style="width: 7.64%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 1.6%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 90.76%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
  </tr>
  <tr>
    <td style="width: 7.64%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.52</div></td>
    <td style="width: 1.6%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 90.76%; 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/874015/000087401515000057/ex10_1.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Second Amended and Restated Strategic Collaboration and License Agreement between the Registrant and Alnylam Pharmaceuticals, Inc. dated January 8, 2015</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed as an exhibit to the Registrant&#8217;s Quarterly Report on Form 10-Q for the quarter ended March 31, 2015 and incorporated herein by reference. Portions of this exhibit have been omitted and separately filed with the SEC with a request for confidential treatment.</span></div></td>
  </tr>
  <tr>
    <td style="width: 7.64%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 1.6%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 90.76%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
  </tr>
  <tr>
    <td style="width: 7.64%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.53</div></td>
    <td style="width: 1.6%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>
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  </tr>
  <tr>
    <td style="width: 7.64%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 1.6%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 90.76%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
  </tr>
  <tr>
    <td style="width: 7.64%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.54</div></td>
    <td style="width: 1.6%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>
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  </tr>
  <tr>
    <td style="width: 7.64%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 1.6%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 90.76%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
  </tr>
  <tr>
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    <td style="width: 1.6%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>
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  </tr>
  <tr>
    <td style="width: 7.64%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 1.6%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 90.76%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
  </tr>
  <tr>
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    <td style="width: 1.6%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>
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  <tr>
    <td style="width: 7.64%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 1.6%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 90.76%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
  </tr>
  <tr>
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  </tr>
</table>
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<div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span>86</span></div>
</div>
<div 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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<table cellpadding="0" cellspacing="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" id="zc62c2a1515584b0498aea00d12922817">
  <tr>
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  <tr>
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  <tr>
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  <tr>
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    <td style="width: 90.76%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
  </tr>
  <tr>
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  <tr>
    <td style="width: 7.64%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td colspan="2" style="width: 1.6%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 90.76%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
  </tr>
  <tr>
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  <tr>
    <td style="width: 7.64%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td colspan="2" style="width: 1.6%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 90.76%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
  </tr>
  <tr>
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  </tr>
  <tr>
    <td style="width: 7.64%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td colspan="2" style="width: 1.6%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 90.76%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
  </tr>
  <tr>
    <td style="width: 7.64%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.63</div></td>
    <td colspan="2" style="width: 1.6%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>
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  </tr>
  <tr>
    <td style="width: 7.64%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td colspan="2" style="width: 1.6%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 90.76%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
  </tr>
  <tr>
    <td style="width: 7.64%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.64</div></td>
    <td colspan="2" style="width: 1.6%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 90.76%; 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/874015/000087401518000105/ex10_1.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">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: 7.64%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td colspan="2" style="width: 1.6%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 90.76%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
  </tr>
  <tr>
    <td colspan="2" 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;">10.65</div></td>
    <td style="width: 1.46%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 90.76%; 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/874015/000087401518000105/ex10_2.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Stock Purchase Agreement by and between the Registrant and Biogen MA Inc.</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, dated April 19, 2018, filed as an exhibit to the Registrant&#8217;s Quarterly Report on Form 10-Q for the quarter ended June 30, 2018 and incorporated herein by reference.</span></div></td>
  </tr>
  <tr>
    <td colspan="2" style="width: 7.78%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 1.46%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 90.76%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
  </tr>
  <tr>
    <td colspan="2" 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: 1.46%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 90.76%; 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/874015/000087401518000128/ex10_1.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Second Amendment to Research, Collaboration, Option and License Agreement by and between the Registrant and Janssen Biotech Inc.</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, dated August 7, 2018, filed as an exhibit to the Registrant&#8217;s Quarterly Report on Form 10-Q for the quarter ended September 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 colspan="2" style="width: 7.78%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 1.46%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 90.76%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
  </tr>
  <tr>
    <td colspan="2" 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;">10.67</div></td>
    <td style="width: 1.46%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 90.76%; 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/874015/000087401519000045/exhibit10_67.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Factor B Development Collaboration, Option and License Agreement by and between the Registrant, F. Hoffmann-La Roche Ltd and Hoffmann-La Roche Inc., dated October 9, 2018,</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> filed as an exhibit to the Registrant&#8217;s Annual Report on Form 10-K for the year ended December 31, 2018 and incorporated herein by reference. Portions of this exhibit have been omitted and separately filed with the SEC with a request for confidential treatment.</span></div></td>
  </tr>
  <tr>
    <td colspan="2" style="width: 7.78%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 1.46%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 90.76%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
  </tr>
  <tr>
    <td colspan="2" 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: 1.46%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>
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  </tr>
  <tr>
    <td colspan="2" style="width: 7.78%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 1.46%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 90.76%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
  </tr>
  <tr>
    <td colspan="2" 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;">10.69</div></td>
    <td style="width: 1.46%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 90.76%; 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/874015/000087401519000045/exhibit10_69.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Amendment #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 colspan="2" style="width: 7.78%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 1.46%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 90.76%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
  </tr>
  <tr>
    <td colspan="2" 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: 1.46%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 90.76%; 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/874015/000087401519000045/exhibit10_70.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Amendment #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 colspan="2" style="width: 7.78%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 1.46%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 90.76%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
  </tr>
  <tr>
    <td colspan="2" 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;">10.71</div></td>
    <td style="width: 1.46%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 90.76%; 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/874015/000114036119014492/ex10_1.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Amendment #1 to Second Amended and Restated Strategic Neurology Drug Discovery and Development Collaboration, Option and License Agreement by and between the Registrant and Biogen MA Inc., dated May 2, 2019</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed as an exhibit to the Registrant&#8217;s Quarterly Report on Form 10-Q for the quarter ended June 30, 2019 and incorporated herein by reference.</span></div></td>
  </tr>
</table>
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<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span>87</span></div>
</div>
<div 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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<table cellpadding="0" cellspacing="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" id="z8652c9fbaf54441e9eb6895928a3c042">
  <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>
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  </tr>
  <tr>
    <td style="width: 7.78%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 1.46%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 90.76%; vertical-align: top; background-color: #FFFFFF;">&#160;</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;">10.73</div></td>
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  <tr>
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    <td style="width: 1.46%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
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    <td style="width: 1.46%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 90.76%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
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  <tr>
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    <td style="width: 1.46%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 90.76%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
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    <td style="width: 7.78%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 1.46%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 90.76%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
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    <td style="width: 1.46%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>
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    <td style="width: 7.78%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 1.46%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 90.76%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
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    <td style="width: 7.78%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 1.46%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 90.76%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
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<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span>88</span></div>
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<table cellpadding="0" cellspacing="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" id="z61eb60bfa99841eebfd98b03e00bbe5c">
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    <td style="width: 7.78%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 1.46%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 90.76%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
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    <td style="width: 90.76%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
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    <td style="width: 1.46%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 90.76%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
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    <td style="width: 1.46%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 90.76%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
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    <td style="width: 1.46%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 90.76%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
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    <td style="width: 7.78%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 1.46%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 90.76%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
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    <td style="width: 90.76%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
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<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="z2f1ccd5a118b45c08e94f338898afa6c">
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<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span>89</span></div>
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</div>
<div><br /></div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">SIGNATURES</div>
<div style="text-align: justify;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> </span><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Pursuant to the requirements of Section 13 or 15(d) of the Securities Exchange Act of 1934, the Registrant has duly caused this report on Form 10-K to be signed on its behalf by the undersigned, thereunto duly authorized on the 24<sup>th</sup> day of February, 2021.</div>
<div style="text-align: center;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> </span><br /></div>
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    <td colspan="2" style="width: 50.19%; vertical-align: top;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">IONIS PHARMACEUTICALS, INC.</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;">&#160;</td>
  </tr>
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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>
  </tr>
  <tr>
    <td style="width: 49.81%; vertical-align: top;">&#160;</td>
    <td style="width: 4.63%; vertical-align: top;">&#160;</td>
    <td style="width: 45.56%; vertical-align: top;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Brett P. Monia., Ph.D.</div></td>
  </tr>
  <tr>
    <td style="width: 49.81%; vertical-align: top;">&#160;</td>
    <td style="width: 4.63%; vertical-align: top;">&#160;</td>
    <td style="width: 45.56%; vertical-align: top;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Chief Executive Officer (Principal executive officer)</div></td>
  </tr>
</table>
<div style="text-align: center;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> </span><br /></div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">POWER OF ATTORNEY</div>
<div style="text-align: center;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> </span><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">KNOW ALL MEN BY THESE PRESENTS, that each person whose signature appears below constitutes and appoints Brett P. Monia and Elizabeth L. Hougen, or any of them, his or her attorney-in-fact, each with the power of substitution, for him or her in any and all capacities, to sign any amendments to this Report, and to file the same, with exhibits thereto and other documents in connection therewith, with the Securities and Exchange Commission, hereby ratifying and confirming all that each of said attorneys-in-fact, or his or her substitute or substitutes, may do or cause to be done by virtue hereof.</div>
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<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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    <td style="width: 30.39%; vertical-align: top; border-bottom: #000000 2px solid;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">/s/ BRETT P. MONIA</div></td>
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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 and Chief Executive Officer</div></td>
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    <td style="width: 16.06%; vertical-align: top;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">February 24, 2021</div></td>
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    <td style="width: 30.39%; vertical-align: top; border-bottom: #000000 2px solid;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">/s/ ELIZABETH L. HOUGEN</div></td>
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    <td style="width: 16.06%; vertical-align: top;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">February 24, 2021</div></td>
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    <td style="width: 30.39%; vertical-align: top; border-bottom: #000000 2px solid;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">/s/ STANLEY T. CROOKE</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;">Executive 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 24, 2021</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 and Senior Strategic Advisor</div></td>
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    <td style="width: 16.06%; vertical-align: top;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">February 24, 2021</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 24, 2021</div></td>
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    <td style="width: 49.28%; vertical-align: top;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Director</div></td>
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    <td style="width: 16.06%; vertical-align: top;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">February 24, 2021</div></td>
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    <td style="width: 30.39%; vertical-align: top; border-bottom: #000000 2px solid;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">/s/ MICHAEL HAYDEN</div></td>
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    <td style="width: 49.28%; vertical-align: top;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Director</div></td>
    <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 24, 2021</div></td>
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    <td style="width: 30.39%; vertical-align: top; border-bottom: #000000 2px solid;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">/s/ JOAN E. HERMAN</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 24, 2021</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;">Joan E. Herman</div></td>
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    <td style="width: 30.39%; vertical-align: top; border-bottom: #000000 2px solid;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">/s/ JOSEPH KLEIN</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 24, 2021</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 Klein, III</div></td>
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    <td style="width: 30.39%; vertical-align: top; border-bottom: #000000 2px solid;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">/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;">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 24, 2021</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 Loscalzo, M.D., Ph.D.</div></td>
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    <td style="width: 30.39%; vertical-align: top; border-bottom: #000000 2px solid;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">/s/ FREDERICK T. MUTO</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 24, 2021</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;">Frederick T. Muto, Esq.</div></td>
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    <td style="width: 49.28%; vertical-align: top;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Director</div></td>
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    <td style="width: 16.06%; vertical-align: top;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">February 24, 2021</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;">Peter N. Reikes</div></td>
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    <td style="width: 30.39%; vertical-align: top; border-bottom: #000000 2px solid;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">/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;">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 24, 2021</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>
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<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">IONIS PHARMACEUTICALS, INC.</div>
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<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">INDEX TO CONSOLIDATED FINANCIAL STATEMENTS</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: 10pt;">Report of Independent Registered Public Accounting Firm</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;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Consolidated Balance Sheets at December 31, </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">2020</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> and </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">2019</span></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;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Consolidated Statements of Comprehensive Income (Loss) for the years ended December 31, </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">2020</span><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;">2019</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> and </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">2018</span></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: 10pt;">Notes to Consolidated Financial Statements</div></td>
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<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">REPORT OF INDEPENDENT REGISTERED PUBLIC ACCOUNTING FIRM</div>
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<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 style="text-align: left;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> </span><br /></div>
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Opinion on the Financial Statements</div>
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<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 &#8220;Company&#8220;) as of December 31, 2020 and 2019, the related consolidated statements of operations, comprehensive income (loss), stockholders&#8217; equity, and cash flows, for each of the three years in the period ended December 31, 2020 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, 2020 and 2019, and the results of its operations and its cash flows for each of the three years in the period ended December 31, 2020, in conformity with U.S. generally accepted accounting principles.</div>
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<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, 2020, based on criteria established in Internal Control-Integrated Framework issued by the Committee of Sponsoring Organizations of the Treadway Commission (2013 framework), and our report dated February 24, 2021 expressed an unqualified opinion thereon.</div>
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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Basis for Opinion</div>
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<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>
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<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 include 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>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Critical Audit Matter</div>
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<div style="text-align: justify; margin-bottom: 12pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The critical audit matter communicated below is a matter arising from the current period audit of the financial statements that was communicated or required to be communicated to the audit committee and that: (1) relates to accounts or disclosures that are material to the financial statements and (2) involved our especially challenging, subjective or complex judgments. The communication of the critical audit matter does not alter in any way our opinion on the consolidated financial statements, taken as a whole, and we are not, by communicating the critical audit matter below, providing a separate opinion on the critical audit matter or on the account or disclosure to which it relates.</div>
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    <td style="width: 86.32%; vertical-align: top;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Realizability of Deferred Tax Assets</div></td>
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    <td style="width: 12.29%; 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>
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    <td style="width: 86.32%; vertical-align: top;"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">As discussed in Note 1 to the consolidated financial statements, the Company records a valuation allowance based on the assessment of the realizability of the Company&#8217;s deferred tax assets. Deferred tax assets are reduced by a valuation allowance if, based on the weight of all available evidence, in management&#8217;s judgment it is more likely than not that some portion, or all, of the deferred tax assets will not be realized. For the year ended December 31, 2020, the Company had net deferred tax assets of $633.4 million and a related valuation allowance of $633.4 million as described in Note 5.</div><div>&#160;</div><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Auditing management&#8217;s assessment of the realizability of its deferred tax assets involved significant judgment because the assessment process is complex, and is based upon assumptions that may be affected by future market or economic conditions.</div></td>
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    <td style="width: 12.29%; 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>
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    <td style="width: 86.32%; vertical-align: top;"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We evaluated and tested the design and operating effectiveness of controls over the Company&#8217;s income tax process, including controls over management&#8217;s scheduling of the future reversal of existing taxable temporary differences, identification and use of available tax planning strategies and projections of future taxable income (loss).</div><div>&#160;</div><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Among other audit procedures performed, we evaluated the assumptions used by the Company to develop the scheduling of the future reversal of existing taxable temporary differences, tax planning strategies, as well as current earnings and anticipated future earnings (losses) used in the Company&#8217;s analysis in determining the valuation allowance on a jurisdiction by jurisdiction basis. We tested the completeness and accuracy of the underlying data used in the Company&#8217;s projections. For example, we compared management&#8217;s forecasts to actual results for the current and historical periods. Furthermore, we evaluated the appropriateness of the assumptions underlying the future projected financial information, as well as management&#8217;s consideration of current operating, industry and economic trends. We also compared the projections of future taxable income (loss) with other forecasted financial information prepared by the Company. In addition, we involved our tax specialists to evaluate the application of tax law in the projections of future taxable income (loss).</div></td>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">/s/ Ernst &amp; Young LLP</div>
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<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>
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<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 24, 2021</div>
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<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">IONIS PHARMACEUTICALS, INC.</div>
<div 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>
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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;">Current assets:</div></td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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  <tr>
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  <tr>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:FiniteLivedIntangibleAssetsNet" id="Fact_35383fdfc944499d99481f4236a96589" contextRef="c20201231" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">27,937</ix:nonFraction></div></td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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  </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 tax assets</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DeferredIncomeTaxAssetsNet" id="Fact_5f2a655af2b4494588eb9fd1c7927ce1" contextRef="c20201231" unitRef="U001" decimals="-3" scale="3" format="ixt:zerodash">&#8212;</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DeferredIncomeTaxAssetsNet" id="Fact_d5da495aeeca4464978a569391184ebe" contextRef="c20191231" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">305,557</ix:nonFraction></div></td>
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  <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;">Deposits and other assets</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherAssetsNoncurrent" id="Fact_028d5e12b53d44efafc7fc6259a8c677" contextRef="c20201231" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">50,034</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherAssetsNoncurrent" id="Fact_0c76b4574810464783e04a0b5fcd3d22" contextRef="c20191231" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">27,633</ix:nonFraction></div></td>
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  <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 assets</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
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  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#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;">Current liabilities:</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AccountsPayableCurrent" id="Fact_d2f4209896534c34b236247e2f014047" contextRef="c20201231" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">17,199</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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  </tr>
  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:EmployeeRelatedLiabilitiesCurrent" id="Fact_6757e467d4ca4989a92e1b0146882726" contextRef="c20201231" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">65,728</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:EmployeeRelatedLiabilitiesCurrent" id="Fact_e13f67f862ed4bf9b0ccd8241eabef36" contextRef="c20191231" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">37,357</ix:nonFraction></div></td>
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  </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 liabilities</div></td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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  </tr>
  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ConvertibleDebtCurrent" id="Fact_a6d3c639a96b430cbd40608aaee204de" contextRef="c20201231" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">293,161</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Current portion of long-term obligations</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:LongTermObligationsCurrent" id="Fact_c3dd012ae5014734b3edfded476645f1" contextRef="c20201231" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">7,301</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:LongTermObligationsCurrent" id="Fact_b637339218424d74ba82205fd72c11a5" contextRef="c20191231" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">2,026</ix:nonFraction></div></td>
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  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 2px;"><div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Current portion of deferred contract revenue</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ContractWithCustomerLiabilityCurrent" id="Fact_dde59dcefdfc41a5aece21fc7e36d234" contextRef="c20201231" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">108,376</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ContractWithCustomerLiabilityCurrent" id="Fact_b5c48cb25c964d7c97633d915cafdb42" contextRef="c20191231" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">118,272</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total current liabilities</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:LiabilitiesCurrent" id="Fact_6dd286ee152042f78be1fe86c4b53e7b" contextRef="c20201231" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">583,250</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:LiabilitiesCurrent" id="Fact_324dbdee5a4a42159831822bf6b85720" contextRef="c20191231" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">273,005</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#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;">Long-term deferred contract revenue</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ContractWithCustomerLiabilityNoncurrent" id="Fact_e76b53d24abc4ce98f4c0bd7bb5c4ee7" contextRef="c20201231" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">424,046</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ContractWithCustomerLiabilityNoncurrent" id="Fact_4f3a8b90ab234988bb31ecd484021c4b" contextRef="c20191231" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">490,060</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ConvertibleDebtNoncurrent" id="Fact_4eab47dc0a1d4b1c9a9acd7ab3519611" contextRef="c20201231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">455,719</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ConvertibleDebtNoncurrent" id="Fact_20d7bf53e413467294f1b30f5e5ea0f9" contextRef="c20191231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">434,711</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#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;"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_b7ce8f233b164fddb7b9bef8a2921d5e" contextRef="c20201231_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_90f07422f1ef4cd796335f941380f7e0" contextRef="c20191231_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">1</ix:nonFraction></ix:nonFraction> percent convertible senior notes</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ConvertibleDebtNoncurrent" id="Fact_fa9ddcff26e244deb6af4ff717c2ed72" contextRef="c20201231_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember" unitRef="U001" decimals="-3" scale="3" format="ixt:zerodash">&#8212;</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ConvertibleDebtNoncurrent" id="Fact_b81d968939c04aae8ac13f6ad19d2814" contextRef="c20191231_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">275,333</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#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 obligations, less current portion</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:LongTermObligationsNoncurrent" id="Fact_4c526f7e2df4476ea452dc42e08d921b" contextRef="c20201231" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">23,409</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:LongTermObligationsNoncurrent" id="Fact_59cacc1d32984d6198584f93759863e0" contextRef="c20191231" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">15,543</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 2px;"><div style="text-align: left; text-indent: -36pt; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Long-term mortgage debt</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:LongTermLoansFromBank" id="Fact_d0bdde965a494bd1967c669121c18b69" contextRef="c20201231" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">59,984</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:LongTermLoansFromBank" id="Fact_b1093c295a3e4d8980c112cd144aa095" contextRef="c20191231" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">59,913</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#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: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total liabilities</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:Liabilities" id="Fact_72e72fa97a344884ae45c7d1457d4c58" contextRef="c20201231" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">1,546,408</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
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  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:CommonStockValue" id="Fact_5f48063ae846417a85a50e82db398716" contextRef="c20201231" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">140</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:CommonStockValue" id="Fact_942a957fd1a642b4a9846b941b383984" contextRef="c20191231" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">140</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#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;">Additional paid-in capital</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AdditionalPaidInCapitalCommonStock" id="Fact_3f85039492a3477ba262bbaf1e3a9940" contextRef="c20201231" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">2,113,646</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#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;">Accumulated other comprehensive loss</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:AccumulatedOtherComprehensiveIncomeLossNetOfTax" id="Fact_7f6094dad8014d18a90ab96ded5f7902" contextRef="c20201231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">21,071</ix:nonFraction></div></td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:AccumulatedOtherComprehensiveIncomeLossNetOfTax" id="Fact_3e9ce1fe826144aea3422b89b11598b2" contextRef="c20191231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">25,290</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;"><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: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Accumulated deficit</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:RetainedEarningsAccumulatedDeficit" id="Fact_6946ee9e730b46ca9324cbc783ed82e1" contextRef="c20201231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">1,249,368</ix:nonFraction></div></td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
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  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total Ionis stockholders&#8217; equity</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockholdersEquity" id="Fact_1ebcc837b8984805befb132fd95881a8" contextRef="c20201231" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">843,347</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockholdersEquity" id="Fact_2815f025bebb4872b942adb7491ee5b7" contextRef="c20191231" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">1,471,094</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 2px;"><div style="text-align: left; text-indent: -18.15pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Noncontrolling interest in Akcea Therapeutics, Inc.</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:MinorityInterest" id="Fact_15a602087f334617867a83b5dd1b29aa" contextRef="c20201231" unitRef="U001" decimals="-3" scale="3" format="ixt:zerodash">&#8212;</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:MinorityInterest" id="Fact_689780f0068e47e98756616aa52d94d0" contextRef="c20191231" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">213,453</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#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: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total stockholders&#8217; equity</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" id="Fact_d61c237c2816416e9904b633d30916b8" contextRef="c20201231" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">843,347</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" id="Fact_0f68a4db9f9b47ad8afdba3a4483a05e" contextRef="c20191231" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">1,684,547</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#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 liabilities and stockholders&#8217; equity</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:LiabilitiesAndStockholdersEquity" id="Fact_801588c240bd4ed6bb876453863968da" contextRef="c20201231" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">2,389,755</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:LiabilitiesAndStockholdersEquity" id="Fact_52b3ab3e91024ab988399c759f32bda8" contextRef="c20191231" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">3,233,112</ix:nonFraction></div></td>
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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><br /></div>
<div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
<div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">F-<span>3</span></div>
</div>
<div style="page-break-after:always;"><hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>
<div></div>
</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; 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 cellpadding="0" cellspacing="0" id="zb78a3c3b174245e0ba6c30a0446a83d8" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <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;"></div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="10" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><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" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2020</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2019</div></td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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  <tr>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_f85a761fec13470182f51d2856db9e79" contextRef="c20190101to20191231_ProductOrServiceAxis_LicensingAndOtherRoyaltiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">17,205</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
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  <tr>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
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  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
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  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
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  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
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  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
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  <tr>
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  <tr>
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  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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  <tr>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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  <tr>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:OtherNonoperatingIncomeExpense" id="Fact_95a44b06b165497c90c92f0ecb837d5d" contextRef="c20180101to20181231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">182</ix:nonFraction></div></td>
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  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 64%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;">&#160;</td>
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  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 64%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#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: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Income tax benefit (expense)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:IncomeTaxExpenseBenefit" id="Fact_25eb94c1a44848a4ae8038f050bdb154" contextRef="c20200101to20201231" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">316,734</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:IncomeTaxExpenseBenefit" id="Fact_5b1c8e20abb84c34b626e66d15f639fe" contextRef="c20190101to20191231" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">43,507</ix:nonFraction></div></td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:IncomeTaxExpenseBenefit" id="Fact_4e00bc85f9de44bc9fae3e310059dd54" contextRef="c20180101to20181231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">291,141</ix:nonFraction></div></td>
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  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 64%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#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 income (loss)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
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  <tr>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
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  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>
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  </tr>
  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;">&#160;</td>
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  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>
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  </tr>
  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:WeightedAverageNumberOfDilutedSharesOutstanding" id="Fact_5a8e2e89a8854d18b716d51e6be5e33a" contextRef="c20180101to20181231" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">134,056</ix:nonFraction></div></td>
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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><br /></div>
<div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
<div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">F-<span>4</span></div>
</div>
<div style="page-break-after:always;"><hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>
<div></div>
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<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">I<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">ONIS PHARMACEUTICALS, INC.</span></div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">CONSOLIDATED STATEMENTS OF COMPREHENSIVE INCOME (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 cellpadding="0" cellspacing="0" id="z635def10a4564b398b501c0dd2ebe78f" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
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    <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;"></div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="10" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><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;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2019</div></td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
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  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>
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  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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  <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 colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Currency translation adjustment</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax" id="Fact_0118d01a0fc0483d942b9e51407b4717" contextRef="c20200101to20201231" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">617</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax" id="Fact_e0cf23c629544136a3b19d99634a49a6" contextRef="c20190101to20191231" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">93</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax" id="Fact_107faab7668f4901940b3c076c0c0ec6" contextRef="c20180101to20181231" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">23</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 64%; padding-bottom: 2px;"><div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Adjustments to other comprehensive loss from purchase of noncontrolling interest of Akcea Therapeutics, Inc.</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:OtherComprehensiveIncomeLossAdjustmentsFromPurchaseOfNoncontrollingInterestOfSubsidiary" id="Fact_8dde645333454befac18a987f4b4ffbb" contextRef="c20180101to20181231" unitRef="U001" decimals="-3" scale="3" format="ixt:zerodash">&#8212;</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#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;">Comprehensive income (loss)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:ComprehensiveIncomeNetOfTaxIncludingPortionAttributableToNoncontrollingInterest" id="Fact_88990aa910f44465b514db16de1b6797" contextRef="c20200101to20201231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">482,547</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ComprehensiveIncomeNetOfTaxIncludingPortionAttributableToNoncontrollingInterest" id="Fact_a94a014398884db3aad264a9afa0f0b9" contextRef="c20190101to20191231" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">309,988</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ComprehensiveIncomeNetOfTaxIncludingPortionAttributableToNoncontrollingInterest" id="Fact_952a61bbba0241e4b821f51c3f0cbaf0" contextRef="c20180101to20181231" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">214,728</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#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;">Comprehensive income (loss) attributable to noncontrolling interest in Akcea Therapeutics, Inc.</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:ComprehensiveIncomeNetOfTaxAttributableToNoncontrollingInterest" id="Fact_0a2ffbf7523a40bfb67425a2f824fdda" contextRef="c20200101to20201231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">35,480</ix:nonFraction></div></td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ComprehensiveIncomeNetOfTaxAttributableToNoncontrollingInterest" id="Fact_835fc2d29a554273b86faf6556c423be" contextRef="c20190101to20191231" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">9,118</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:ComprehensiveIncomeNetOfTaxAttributableToNoncontrollingInterest" id="Fact_7354d55541b84356989b29706bcadb0e" contextRef="c20180101to20181231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">58,781</ix:nonFraction></div></td>
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  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 64%; padding-bottom: 4px; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Comprehensive income (loss) attributable to Ionis Pharmaceuticals, Inc. common stockholders</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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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><br /></div>
<div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
<div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">F-<span>5</span></div>
</div>
<div style="page-break-after:always;"><hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>
<div></div>
</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;"><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;">Years Ended December 31, 2020, 2019 and 2018</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>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Equity</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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  </tr>
  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent" id="Fact_bcb33dc46de04209908df558c7517ab6" contextRef="c20190101to20191231_StatementEquityComponentsAxis_CommonStockMember" unitRef="U001" decimals="-3" scale="3" format="ixt:zerodash">&#8212;</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent" id="Fact_9f6c8f24969b40efb8f65b0be7d4817c" contextRef="c20190101to20191231_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember" unitRef="U001" decimals="-3" scale="3" format="ixt:zerodash">&#8212;</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent" id="Fact_dd492197a00544849a621869a65ed107" contextRef="c20190101to20191231_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">6,633</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent" id="Fact_a284ae016f8a4eb1bc5f2f2f8761f20f" contextRef="c20190101to20191231_StatementEquityComponentsAxis_RetainedEarningsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:zerodash">&#8212;</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent" id="Fact_64b3303b5db44e0286c02284e1873d25" contextRef="c20190101to20191231_StatementEquityComponentsAxis_ParentMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">6,633</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent" id="Fact_1879a83c61794d7cb07b68b08723adfb" contextRef="c20190101to20191231_StatementEquityComponentsAxis_NoncontrollingInterestMember" unitRef="U001" decimals="-3" scale="3" format="ixt:zerodash">&#8212;</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent" id="Fact_bf6e59bfd66742789d37172b5da252f6" contextRef="c20190101to20191231" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">6,633</ix:nonFraction></div></td>
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  </tr>
  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
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  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
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  </tr>
  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 20%;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Change in unrealized gains, net of tax</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent" id="Fact_3e9a51c2a8924e478a8580d8341d5f36" contextRef="c20200101to20201231_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember" unitRef="U001" decimals="-3" scale="3" format="ixt:zerodash">&#8212;</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 20%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Foreign currency translation</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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  <tr>
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  <tr>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
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  <tr>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" id="Fact_abcf57a241dd478b9725dbabd25b2718" contextRef="c20201231" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">843,347</ix:nonFraction></div></td>
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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><br /></div>
<div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
<div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">F-<span>6</span></div>
</div>
<div style="page-break-after:always;"><hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>
<div></div>
</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; 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 cellpadding="0" cellspacing="0" id="z413232ff7f5b4dffa80b931edf661690" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <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;"></div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2019</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2018</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#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 colspan="1" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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  <tr>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;">&#160;</td>
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  <tr>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 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: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Amortization of patents</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AmortizationOfIntangibleAssets" id="Fact_c4419687fb464fe5bdc6e0d2984bef36" contextRef="c20200101to20201231" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">2,064</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AmortizationOfIntangibleAssets" id="Fact_2510d199eca04ba290db4822e474a069" contextRef="c20190101to20191231" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">1,912</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AmortizationOfIntangibleAssets" id="Fact_dfcf2be324b646d9bb90e538cfcfa5d7" contextRef="c20180101to20181231" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">1,822</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#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 colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AccretionAmortizationOfDiscountsAndPremiumsInvestments" id="Fact_19b1a8aca8b7454d8d920b65112f9717" contextRef="c20200101to20201231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">11,521</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Amortization of debt issuance costs</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AmortizationOfFinancingCosts" id="Fact_b85286437b974418ba977d6f06debc76" contextRef="c20200101to20201231" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">2,578</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AmortizationOfFinancingCosts" id="Fact_a644e66590634fa5857536f88b90ec7a" contextRef="c20190101to20191231" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">1,942</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AmortizationOfFinancingCosts" id="Fact_8299ca7b84184a219ca22bdd8885ded6" contextRef="c20180101to20181231" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">1,810</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#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 convertible senior notes discount</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AmortizationOfDebtDiscountPremium" id="Fact_c6a08bf487994614bcb0094e8c8ffdb8" contextRef="c20200101to20201231" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">36,157</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AmortizationOfDebtDiscountPremium" id="Fact_a26c3943aee0441994aee8f5be710103" contextRef="c20180101to20181231" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">33,363</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#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;">Stock-based compensation expense</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ShareBasedCompensation" id="Fact_de86964f1c204681a24953a828812433" contextRef="c20200101to20201231" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">230,117</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ShareBasedCompensation" id="Fact_b7ce371b025e4c42b0adacb5ab3929a4" contextRef="c20190101to20191231" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">146,574</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
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  <tr>
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  <tr>
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  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;">&#160;</td>
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  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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  </tr>
  <tr>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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  </tr>
  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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  </tr>
  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
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  </tr>
  <tr>
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  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 64%;"><div style="text-align: left; text-indent: -9pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Income taxes</div></td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 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: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Accrued compensation</div></td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:IncreaseDecreaseInOtherEmployeeRelatedLiabilities" id="Fact_c2e1e6792bbf4d45bb9581a0838da942" contextRef="c20190101to20191231" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">8,089</ix:nonFraction></div></td>
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  <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 liabilities and deferred rent</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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  </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;">Deferred contract revenue</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:IncreaseDecreaseInContractWithCustomerLiability" id="Fact_860c87bb13ca432ab6413fcb41ab7d48" contextRef="c20190101to20191231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">119,283</ix:nonFraction></div></td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:IncreaseDecreaseInContractWithCustomerLiability" id="Fact_9c03c531ef514d558aa7fca25bb6b718" contextRef="c20180101to20181231" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">494,254</ix:nonFraction></div></td>
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  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 64%; padding-bottom: 2px;"><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 operating activities</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:NetCashProvidedByUsedInOperatingActivities" id="Fact_19c256c737ca49a4a82b43e1d4907fd7" contextRef="c20200101to20201231" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">35,892</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:NetCashProvidedByUsedInOperatingActivities" id="Fact_6ac8228472434c89928ff5906d8cdfa8" contextRef="c20190101to20191231" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">345,627</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
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  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Investing activities:</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#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;">Purchases of short-term investments</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:PaymentsToAcquireAvailableForSaleSecuritiesDebt" id="Fact_e72b6b733f32469391537642ed9f915f" contextRef="c20200101to20201231" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">1,570,410</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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  <tr>
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  </tr>
  <tr>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Acquisition of licenses and other assets, net</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 64%; padding-bottom: 2px;"><div style="text-align: left; text-indent: -9pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Purchase of strategic investments</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:PaymentsToAcquireOtherInvestments" id="Fact_62fe3844a7e8414ea863aff8f888c1ce" contextRef="c20180101to20181231" unitRef="U001" decimals="-3" scale="3" format="ixt:zerodash">&#8212;</ix:nonFraction></div></td>
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  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net cash provided by (used in) investing activities</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:NetCashProvidedByUsedInInvestingActivities" id="Fact_f34b0cc23b5d447c95919927abae52a5" contextRef="c20200101to20201231" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">274,477</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:NetCashProvidedByUsedInInvestingActivities" id="Fact_25c5a36f9c66441bbadcb049e1be0f09" contextRef="c20180101to20181231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">929,563</ix:nonFraction></div></td>
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  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 64%;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Financing activities:</div></td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#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 colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ProceedsFromIssuanceOfSharesUnderIncentiveAndShareBasedCompensationPlansIncludingStockOptions" id="Fact_9766979c83c547faaf9db39fd1ec8b13" contextRef="c20200101to20201231" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">52,036</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ProceedsFromIssuanceOfSharesUnderIncentiveAndShareBasedCompensationPlansIncludingStockOptions" id="Fact_e8614ff277e9476fabd71fcec8d4876c" contextRef="c20190101to20191231" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">119,657</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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  </tr>
  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:PaymentsRelatedToTaxWithholdingForShareBasedCompensation" id="Fact_0355270d749349ec8d585f6e041767cc" contextRef="c20180101to20181231" unitRef="U001" decimals="-3" scale="3" format="ixt:zerodash">&#8212;</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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  <tr>
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  <tr>
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  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents" id="Fact_ad3a4e4b42454d7f972b7be959dc74c6" contextRef="c20171231" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">129,630</ix:nonFraction></div></td>
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  </tr>
  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
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</table>
<div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
<div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">F-<span>7</span></div>
</div>
<div style="page-break-after:always;"><hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>
<div></div>
</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; 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 cellpadding="0" cellspacing="0" id="z34fb7706315e4df4a746e88c9c3d9bd4" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
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  <tr>
    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
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  </tr>
  <tr>
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    <td colspan="2" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 64%;"><div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Income taxes paid</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
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<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">See accompanying notes.</div>
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<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">F-<span>8</span></div>
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<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">IONIS PHARMACEUTICALS, INC.</div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">NOTES TO CONSOLIDATED FINANCIAL STATEMENTS</div>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">1. Organization and Significant Accounting Policies</div>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Basis of Presentation</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In our consolidated financial statements we included the accounts of Ionis Pharmaceuticals, Inc. and the consolidated results of our subsidiary, Akcea Therapeutics, Inc. and its wholly owned subsidiaries (&#8220;we&#8221;, &#8220;us&#8221; or &#8220;our&#8221;). We formed Akcea in December 2014. In July 2017, Akcea completed an initial public offering, or IPO. Prior to Akcea&#8217;s IPO in July 2017, we owned </span><ix:nonFraction name="us-gaap:MinorityInterestOwnershipPercentageByParent" id="Fact_a88597664460426696b9ccf265c067d6" contextRef="c20170630_OwnershipAxis_AkceaTherapeuticsIncMember" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">100</ix:nonFraction> percent<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> of Akcea. In October 2020, we acquired the shares of Akcea&#8217;s common stock we did not own. We will refer to this transaction as the Akcea Acquisition throughout the remainder of this document. </span>See Note 7, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Akcea Acquisition</span>, in the Notes to the Consolidated Financial Statements for further details.<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> We reflected changes in our ownership percentage in our financial statements as an adjustment to noncontrolling interest in the period the change occurred.</span></div>
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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Organization and Business Activity</div>
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<div style="text-align: justify; text-indent: 36pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> </span><br /></div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We incorporated in California on January 10, 1989. In conjunction with our IPO, we reorganized as a Delaware corporation in April 1991. We were organized principally to develop human therapeutic medicines using antisense technology. In December 2015, we changed our name from Isis Pharmaceuticals, Inc. to Ionis Pharmaceuticals, Inc.</div>
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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Basic and Diluted Net Income (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; font-style: italic;">Basic net income (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;">We compute basic net income (loss) per share by dividing the total net income (loss) attributable to our common stockholders by our weighted-average number of common shares outstanding during the period.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The calculation of total net income (loss) attributable to our common stockholders for each year considered our net income (loss) for Ionis on a stand-alone basis plus our share of Akcea&#8217;s net income (loss) for the period. To calculate the portion of Akcea&#8217;s net income (loss) attributable to our ownership for each year, we multiplied Akcea&#8217;s income (loss) per share by the weighted average shares we owned in Akcea during the period. As a result of this calculation, our total net income (loss) available to Ionis common stockholders for the calculation of net income (loss) per share is different than net income (loss) attributable to Ionis Pharmaceuticals, Inc. common stockholders in our consolidated statements of operations for each year.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our basic net income (loss) per share was calculated as follows (in thousands, except per share amounts):</div>
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<table cellpadding="0" cellspacing="0" id="z52a07e9978cc42e1b09d31421865a2e3" 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" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Weighted</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Average Shares</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Owned in Akcea</div></td>
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    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Akcea</span>&#8217;<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">s</span></div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Net Loss</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Per Share</div></td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Basic Net Loss</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Per Share</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Calculation</div></td>
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  <tr>
    <td valign="bottom" style="vertical-align: top; width: 64%; background-color: #CCEEFF; white-space: nowrap;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Akcea&#8217;s net loss in the pre-acquisition period attributable to our ownership</div></td>
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  <tr>
    <td valign="bottom" style="vertical-align: top; width: 64%; padding-bottom: 2px; white-space: nowrap;"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Akcea&#8217;s net loss in the post-acquisition period attributable to our ownership</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:NetIncomeLoss" id="Fact_9621979100a446efadb016e2ff091a8c" contextRef="c20201101to20201231_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">85,987</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;"><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: top; width: 64%; background-color: #CCEEFF; white-space: nowrap;"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Akcea&#8217;s total net loss attributable to our ownership</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: top; width: 64%; padding-bottom: 2px; white-space: nowrap;"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Ionis&#8217; stand-alone net loss</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; white-space: nowrap;">&#160;</td>
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  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net loss available to Ionis common stockholders</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>
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<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">F-<span>9</span></div>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
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  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>
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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><ix:continuation id="Text_6092f09ab86544e48217f477806653e816" continuedAt="Text_6092f09ab86544e48217f477806653e817"><ix:continuation id="Text_87be9d1f99044181a322729aef92249126" continuedAt="Text_87be9d1f99044181a322729aef92249127">
<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 income 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;">For the year ended December 31, 2020, we incurred a net loss; therefore, we did not include dilutive common equivalent shares in the computation of diluted net loss per share because the effect would have been anti-dilutive. Common stock from the following would 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;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">For the years ended December 31, 2019 and 2018, we had net income available to Ionis common stockholders. As a result, we computed diluted net income per share using the weighted-average number of common shares and dilutive common equivalent shares outstanding during each period.</span> We calculated our diluted net income per share as follows <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(in thousands except per share amounts):</span></div>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
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  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
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  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
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  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:IncrementalCommonSharesAttributableToEmployeeStockPurchasePlan" id="Fact_63435561706d411bada0a6048a8b479f" contextRef="c20190101to20191231" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">18</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
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  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
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  <tr>
    <td valign="bottom" style="vertical-align: top; width: 64%; padding-bottom: 4px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:WeightedAverageNumberOfDilutedSharesOutstanding" id="Fact_8f4199f02a7c4375b1908349b2e11384" contextRef="c20180101to20181231" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">134,056</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br /></div>
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<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">For each year presented, the calculation excluded our convertible senior notes because the effect on diluted earnings per share was anti-dilutive.</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;">Revenue Recognition</div>
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<div><br /></div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-decoration: underline;">Our Revenue Sources</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 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 in deferred revenue on our consolidated balance sheet.</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;">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 will also recognize as commercial revenue sales milestone payments and royalties we earn under our other partnerships.</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;">Commercial Revenue: Product sales, 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 added product sales from TEGSEDI to our commercial revenue in the fourth quarter of 2018 and we added product sales from WAYLIVRA to our commercial revenue in the third quarter of 2019. </span>In the U.S., we distribute TEGSEDI through an exclusive distribution agreement with a third-party logistics company, or 3PL, that takes title to TEGSEDI. The 3PL is our sole customer in the U.S. The 3PL then distributes TEGSEDI to a specialty pharmacy and a specialty distributor, which we collectively refer to as wholesalers, who then distribute TEGSEDI to health care providers and patients.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In Europe, through 2020 we sold TEGSEDI and WAYLIVRA to hospitals and pharmacies using 3PLs as distributors. Beginning in 2021, we are commercializing TEGSEDI and WAYLIVRA in Europe through a distribution agreement with Swedish Orphan Biovitrum AB, or Sobi, an international biopharmaceutical company that focuses on rare diseases. Under the terms of this agreement, we retained the marketing authorization for both medicines 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;">In Latin America beginning in 2020, we sold TEGSEDI and WAYLIVRA to our partner, PTC Therapeutics. Under our collaboration agreement with PTC, PTC is commercializing TEGSEDI and WAYLIVRA in Latin America and Caribbean countries.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We often 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, research and development, or R&amp;D, services, and manufacturing services.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We provide details about our collaboration agreements in Note 6, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Collaborative Arrangements and Licensing Agreements.</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">&#xA0;</span>Under each collaboration note we discuss our specific revenue recognition conclusions, including our significant performance obligations under each collaboration.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We use a five-step process to determine the amount of revenue we should recognize and when we should recognize it. The five step process is as follows:</div>
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    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Identify the contract</div></td>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Accounting rules require us to first determine if we have a contract with our partner, including confirming that we have met each of the following criteria:</div>
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    <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: 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: 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: 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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    <td style="width: 18pt; vertical-align: top; align: right;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; font-style: italic;">2</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; font-style: italic;">.</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; font-weight: bold;">Identify the performance obligations</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 next identify our performance obligations, which represent the distinct goods and services we are required to provide under the contract. We typically have only <ix:nonFraction name="ions:RevenueFromContractWithCustomerNumberOfPerformanceObligationsAtInceptionOfContract" id="Fact_2f483f7d09d0477f95e6f58a2f9fce97" contextRef="c20200101to20201231" unitRef="U005" decimals="INF" scale="0" format="ixt-sec:numwordsen">one</ix:nonFraction> performance obligation at the inception of a contract, which is to perform R&amp;D services.</div>
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<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">F-<span>11</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;">Often we enter into a collaboration agreement in which we provide our partner with an option to license a medicine in the future. We may also provide our partner with an option to request that we provide additional goods or services in the future, such as active pharmaceutical ingredient, or API. We evaluate whether these options are material rights at the inception of the agreement. If we determine an option is a material right, we will consider the option a separate performance obligation. Historically, we have concluded that the options we grant to license a medicine in the future or to provide additional goods and services as requested by our partner are not material rights because these items are contingent upon future events that may not occur and are not priced at a significant discount. When a partner exercises its option to license a medicine or requests additional goods or services, then we identify a new performance obligation for that item</span>.</div>
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<div 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; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">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; font-weight: bold;">Determine the transaction price</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 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 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;">Milestone payments are our most common type of variable consideration. We recognize milestone payments using the most likely amount method because we will either receive the milestone payment or we will not, which makes the potential milestone payment a binary event. The most likely amount method requires us to determine the likelihood of earning the milestone payment. We include a milestone payment in the transaction price once it is probable we will achieve the milestone event. Most often, we do not consider our milestone payments probable until we or our partner achieve the milestone event because the majority of our milestone payments are contingent upon events that are not within our control and/ or are usually based on scientific progress which is inherently uncertain. For example, in the </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">fourth</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> quarter of </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">2020</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, we earned</span> a $<ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_c1c41f960a754a9f9617c952a530c029" contextRef="c20201001to20201231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJuly2015WithAstrazenecaMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">20</ix:nonFraction> million <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">milestone payment from AstraZeneca when AstraZeneca initiated a Phase </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">2</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">b study for ION</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">449</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, our medicine in development targeting PCSK</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">9</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> to lower LDL-cholesterol. We did not consider the milestone payment probable until AstraZeneca achieved the milestone event because advancing ION</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">449</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> was contingent on AstraZeneca initiating a Phase </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">2</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">b study and was not within our control. We recognized the milestone payment in full in the period the milestone event was achieved because we did not have any remaining performance obligations related to the milestone payment</span>.</div>
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    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">4.</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; font-weight: bold;">Allocate the transaction price</div></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;">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 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: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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>
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    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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>
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    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Estimated contractual milestone payments we may receive;</div></td>
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    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Expenses we expect to incur;</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;">Estimated income taxes; and</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;">A discount rate.</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 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: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The number of internal hours we estimate we will spend performing these services;</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;">The estimated cost of work we will perform;</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;">The estimated cost of work that we will contract with third parties to perform; and</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;">The estimated cost of API we will use.</div></td>
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<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: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Recognize revenue</div></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;">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 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;">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.</span> Refer to Note 6, <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 the cumulative catch up adjustment we made.</div>
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<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following are examples of when we typically recognize revenue based on the types of payments we receive.</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="text-decoration: underline;">Commercial Revenue: SPINRAZA royalties and Licensing and other royalty revenue</span></div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We recognize royalty revenue, including royalties from SPINRAZA sales, in the period in which the counterparty sells the related product and recognizes the related revenue, which in certain cases may require us to estimate our royalty revenue</span>.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><span style="text-decoration: underline;">Commercial Revenue: Product sales, net</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 recognize product sales in the period when our customer obtains control of our products, which occurs at a point in time upon transfer of title to the customer. We classify payments to customers or other parties in the distribution channel for services that are distinct and priced at fair value as selling, general and administrative, or SG&amp;A, expenses in our consolidated statements of operations. Otherwise, payments to customers or other parties in the distribution channel that do not meet those criteria are classified as a reduction of revenue, as discussed further below. We exclude from revenues taxes collected from customers relating to product sales and remitted to governmental authorities</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 record product sales at our net sales price, or transaction price. We include in our transaction price estimated reserves for discounts, returns, chargebacks, rebates and other allowances that we offer within contracts between us and our customers, wholesalers, health care providers and other indirect customers. We estimate our reserves using the amounts we have earned or what we can claim on the associated sales. We classify our reserves as a reduction of accounts receivable when we are not required to make a payment or as a current liability when we are required to make a payment. In certain cases, our estimates include a range of possible outcomes that are probability weighted for relevant factors such as our historical experience, current contractual and statutory requirements, specific known market events and trends, industry data and forecasted customer buying and payment patterns. Overall, our reserves reflect our best estimates under the terms of our respective contracts. When calculating our reserves and related product sales, we only recognize amounts to the extent that we consider it probable that we would not have to reverse in a future period a significant amount of the cumulative sales we previously recognized. The actual amounts we receive may ultimately differ from our reserve estimates. If actual amounts in the future vary from our estimates, we will adjust these estimates, which would affect our net product sales in the respective period</span>.</div>
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<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following are the components of variable consideration related to product sales:</div>
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<div style="text-align: justify; margin-left: 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;">Chargebacks: </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In the U.S., we estimate obligations resulting from contractual commitments with the government and other entities to sell products to qualified healthcare providers at prices lower than the list prices charged to our U.S. customer. Our U.S. customer charges us for the difference between what it pays for the product and the selling price to the qualified healthcare providers. We also estimate the amount of chargebacks related to our estimated product remaining in the distribution channel at the end of the reporting period that we expect our customer to sell to healthcare providers in future periods. We record these reserves as a reduction to contracts receivable on our consolidated balance sheet</span>.</div>
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<div style="text-align: justify; margin-left: 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;">Government rebates</span><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;">We are subject to discount obligations under government programs, including Medicaid and Medicare programs in the U.S. and we record reserves for government rebates based on statutory discount rates and estimated utilization. We estimate Medicaid and Medicare rebates based on a range of possible outcomes that are probability weighted for the estimated payer mix. We record these reserves as an accrued liability on our consolidated balance sheet with a corresponding offset reducing our product sales in the same period we recognize the related sale. For Medicare, we also estimate the number of patients in the prescription drug coverage gap for whom we will owe an additional liability under the Medicare Part D program. On a quarterly basis, we update our estimates and record any adjustments in the period that we identify the adjustments</span>.</div>
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<div style="text-align: justify; margin-left: 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;">Managed care rebates: </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We are subject to rebates in connection with agreements with certain contracted commercial payers. We record these rebates as a liability on our consolidated balance sheet in the same period we recognize the related revenue. We estimate our managed care rebates based on our estimated payer mix and the applicable contractual rebate rate</span>.</div>
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<div style="text-align: justify; margin-left: 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;">Trade discounts: </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We provide customary invoice discounts on product sales to our U.S. customer for prompt payment. We record this discount as a reduction of product sales in the period in which we recognize the related product revenue</span>.</div>
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<div style="text-align: justify; margin-left: 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;">Distribution services</span>: <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We receive and pay for various distribution services from our U.S. and European customers (prior to our agreement with Sobi) and wholesalers in the U.S. We classify the costs for services we receive that are either not distinct from the sale of the product or for which we cannot reasonably estimate the fair value as a reduction of product sales. To the extent that the services we receive are distinct from the sale of the product, we classify the costs for such services as SG&amp;A expenses.</span></div>
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<div style="text-align: justify; margin-left: 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;">Product returns: </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Our U.S. customer has return rights and the wholesalers have limited return rights primarily related to the product&#8217;s expiration date. We estimate the amount of product sales that our customer may return. We record our return estimate as an accrued refund liability on our consolidated balance sheet with a corresponding offset reducing our product sales in the same period we recognize the related sale. Based on our distribution model for product sales, contractual inventory limits with our customer and wholesalers and the price of the product, we have had minimal returns to date and we believe we will continue to have minimal returns in the U.S. Our European customers generally only take title to the product after they receive an order and therefore they do not maintain excess inventory levels of our products. Accordingly, we have limited return risk in Europe and we do not estimate returns in Europe</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;"><span style="text-decoration: underline;">Research and development revenue under collaboration agreements:</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;"><span style="text-decoration: underline;">Upfront payments</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;">When we enter into a collaboration agreement with 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. For example, under our collaboration agreement with Roche to</span><span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> develop IONIS-FB-L</span><sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> for the treatment of complement-mediated diseases, we received a $</span><ix:nonFraction name="ions:UpfrontPaymentReceived" id="Fact_80c50f2105fc45ff909730144a25f529" contextRef="c20181001to20181231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">75</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million upfront payment in the fourth quarter of 2018. We allocated the upfront payment to our single performance obligation, R&amp;D services. We are amortizing the $</span><ix:nonFraction name="ions:UpfrontPaymentReceived" id="Fact_b04a5042e2c84665977aa473309829e0" contextRef="c20181001to20181231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">75</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million upfront payment using an input method over the estimated period of time we are providing 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; font-style: italic;"><span style="text-decoration: underline;">Milestone payments</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 are required to include additional consideration in the transaction price when it is probable. We typically include milestone payments for R&amp;D services in the transaction price when they are achieved. We include these milestone payments when they are achieved because typically there is considerable uncertainty in the research and development processes that trigger these payments. Similarly, we include approval milestone payments in the transaction price once the medicine is approved by the applicable regulatory agency. We will recognize sales-based milestone payments in the period in which we achieve the milestone under the sales-based royalty exception allowed under accounting rules.</div>
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<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">F-<span>14</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 recognize milestone payments that relate to an ongoing performance obligation over our period of performance. For example, in the </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">fourth</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> quarter of </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">2020</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, we achieved a</span> $<ix:nonFraction name="ions:RevenueFromContractWithCustomerTransactionPriceAdditions" id="Fact_80e6817b8d324f519b9137101cbac5f6" contextRef="c20201001to20201231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember" unitRef="U001" decimals="-5" scale="6" format="ixt:numdotdecimal">7.5</ix:nonFraction>&#xA0;<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">million milestone payment from Biogen when we advanced</span>&#xA0;<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">a </span>target under our 2018 strategic collaboration.<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> We added this payment to the transaction price and allocated it to our R&amp;D services performance obligation. We are recognizing revenue related to this milestone payment over our estimated period of performance</span>.</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. For example, in the third quarter of 2020, we recognized $<ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_e6b50824c73a4c4eb69b8382e1c56121" contextRef="c20200701to20200930_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">18</ix:nonFraction> million in milestone payments when Biogen initiated a Phase 1/2 trial for <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">ION464, our medicine in development targeting alpha-synuclein to treat patients with multiple system atrophy</span>. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We concluded that the milestone payments were not related to our R&amp;D services performance obligation. Therefore, we recognized the milestone payments in full in the third quarter of 2020.</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 generally recognize as revenue the total amount we determine to be the relative stand-alone selling price of a license when we deliver the license to our partner. This is because our partner has full use of the license and we do not have any additional performance obligations related to the license after delivery. For example, in the </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">fourth</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> quarter of </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">2020</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_252d579bed4a46b0bfef24e7b48677b2" contextRef="c20201001to20201231_ProductOrServiceAxis_Ion455Member_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJuly2015WithAstrazenecaMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">30</ix:nonFraction>&#xA0;<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">million license fee from AstraZeneca when AstraZeneca licensed ION</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">455</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, an investigational medicine in development to treat nonalcoholic steatohepatitis, or 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;"><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>For example, in the fourth quarter of 2020, we earned a $<ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_9aa225f0eeb44601a1c07a22cc707fd6" contextRef="c20201001to20201231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2004WithAlnylamPharmaceuticalsIncMember" unitRef="U001" decimals="-5" scale="6" format="ixt:numdotdecimal">41.2</ix:nonFraction> million sublicense fee from Alnylam Pharmaceuticals for its sublicense of our technology to Sanofi Genzyme.</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;">Amendments to Agreements</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; align: right; 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: 18pt; vertical-align: top; align: right; 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 at a stand-alone selling price.</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 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 adjustment.</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;">For example, in May 2015, we entered into an exclusive license agreement with Bayer to develop and commercialize IONIS-FXI</span><sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> for the prevention of thrombosis. As part of the agreement, Bayer paid us a $</span><ix:nonFraction name="ions:UpfrontPaymentReceived" id="Fact_0d6056e1b6644d9c9d653098b4049ca7" contextRef="c20150501to20150531_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMay2015WithBayerMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">100</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million upfront payment. At the onset of the agreement, we were responsible for completing a Phase 2 study of IONIS-FXI</span><sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> in people with end-stage renal disease on hemodialysis and for providing an initial supply of API. In February 2017, we amended our agreement with Bayer to advance IONIS-FXI</span><sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> and to initiate development of IONIS-FXI-L</span><sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, which Bayer licensed. As part of the 2017 amendment, Bayer paid us $</span><ix:nonFraction name="ions:UpfrontPaymentReceived" id="Fact_a9a1805954f64878a93a25b8bdc51336" contextRef="c20170201to20170228_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementAmendedInFebruary2017WithBayerMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">75</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million. We are also eligible to receive milestone payments and tiered royalties on gross margins of IONIS-FXI</span><sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> and IONIS-FXI-L</span><sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. Under the 2017 amendment, we concluded we had a new agreement with </span><ix:nonFraction name="ions:RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations" id="Fact_d7f40585d07e4c20b3f340621339c834" contextRef="c20170228_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementAmendedInFebruary2017WithBayerMember" unitRef="U005" decimals="INF" scale="0" format="ixt-sec:numwordsen">three</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> performance obligations. These performance obligations were to deliver the license of IONIS-FXI-L</span><sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, to provide R&amp;D services and to deliver API. We allocated the $</span><ix:nonFraction name="ions:RevenueFromContractWithCustomerTransactionPrice" id="Fact_b4cb5c3382b24bcaab84c7f899cd4bb0" contextRef="c20170228_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementAmendedInFebruary2017WithBayerMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">75</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million transaction price to these performance obligations. Refer to Note 6, </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Collaborative Arrangements and Licensing Agreements</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, </span>in our audited financial statements included in our Annual Report on Form 10-K for the year ended December 31, 2019 <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">for further discussion of the Bayer 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;">Multiple agreements</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; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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>
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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;">Whether the amount of consideration in one contract depends on the price or performance of the other agreement; or</div></td>
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    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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;">For example, in the second quarter of 2018, we entered into <ix:nonFraction name="ions:NumberOfAgreementsWithCollaborationPartner" id="Fact_2c7da156332f416f88550ff96ae19478" contextRef="c20180401to20180630_MajorCustomersAxis_BiogenIncMember" unitRef="U006" decimals="INF" scale="0" format="ixt-sec:numwordsen">two</ix:nonFraction> separate agreements with Biogen at the same time: <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">a new strategic neurology collaboration agreement and a stock purchase agreement, or SPA. We evaluated the Biogen agreements to determine whether we should treat the agreements separately or combine them. We considered that the agreements were negotiated concurrently and in contemplation of </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">one</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> another. Based on these facts and circumstances, we concluded that we should evaluate the provisions of the agreements on a combined basis</span><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;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Our contracts receivable balance represents the amounts we have billed our partners or customers and that are due to us unconditionally for goods we have delivered or services we have performed. When we bill our partners or customers with payment terms based on the passage of time, we consider the contracts receivable to be unconditional. We typically receive payment within one </span><span style="-sec-ix-hidden:Fact_e2c2673a057f412ebd5831ca8712546a">quarter</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> of billing our partner or customer</span>.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">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 on our consolidated balance sheet.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We are often entitled to bill our customers and receive payment from our customers in advance of our obligation to provide services or transfer goods to our partners. In these instances, we include the amounts in deferred revenue on our consolidated balance sheet.</span> During the years ended December 31, 2020 and 2019, we recognized $<ix:nonFraction name="us-gaap:ContractWithCustomerLiabilityRevenueRecognized" id="Fact_7a9ec3bea8ad464ca6e12c6aa16435cd" contextRef="c20200101to20201231" unitRef="U001" decimals="-5" scale="6" format="ixt:numdotdecimal">100.4</ix:nonFraction> million and $<ix:nonFraction name="us-gaap:ContractWithCustomerLiabilityRevenueRecognized" id="Fact_ced6b030f6d146bb91eabbce81e6f413" contextRef="c20190101to20191231" unitRef="U001" decimals="-5" scale="6" format="ixt:numdotdecimal">159.5</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 style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our cost of products sold includes 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 products sold. Prior to obtaining regulatory approval of TEGSEDI in July 2018 and WAYLIVRA in May 2019, we expensed as research and development expenses a significant portion of the costs we incurred to produce the initial commercial launch supply for each medicine.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our research and development expenses include wages, benefits, facilities, supplies, external services, clinical trial and manufacturing costs and other expenses that are directly related to our research and development operations. We expense research and development costs as we incur them. When we make payments for research and development services prior to the services being rendered, we record those amounts as prepaid assets on our consolidated balance sheet and we expense them as the services are provided. For the years ended December 31, 2020, 2019 and 2018, research and development expenses were $<ix:nonFraction name="us-gaap:ResearchAndDevelopmentExpense" id="Fact_d0c1565159a044b595630e050bb43a4e" contextRef="c20200101to20201231" unitRef="U001" decimals="-5" scale="6" format="ixt:numdotdecimal">531.0</ix:nonFraction> million, $<ix:nonFraction name="us-gaap:ResearchAndDevelopmentExpense" id="Fact_0114d1a3cfd445bbb2a6b5bc9fba079f" contextRef="c20190101to20191231" unitRef="U001" decimals="-5" scale="6" format="ixt:numdotdecimal">461.5</ix:nonFraction> million and $<ix:nonFraction name="us-gaap:ResearchAndDevelopmentExpense" id="Fact_203e9d3fa0b14eca9d0edbb437f4f325" contextRef="c20180101to20181231" unitRef="U001" decimals="-5" scale="6" format="ixt:numdotdecimal">411.9</ix:nonFraction> million, respectively. A portion of the costs included in research and development expenses are costs associated with our partner agreements. For the years ended December 31, 2020, 2019 and 2018, research and development costs of approximately $<ix:nonFraction name="us-gaap:ResearchAndDevelopmentExpense" id="Fact_802d7e1d88dd4400b573e6ee2246659a" contextRef="c20200101to20201231_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsMember" unitRef="U001" decimals="-5" scale="6" format="ixt:numdotdecimal">49.8</ix:nonFraction> million, $<ix:nonFraction name="us-gaap:ResearchAndDevelopmentExpense" id="Fact_216c3f8ce5e44d2c80d7b536e2b7febb" contextRef="c20190101to20191231_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsMember" unitRef="U001" decimals="-5" scale="6" format="ixt:numdotdecimal">83.2</ix:nonFraction> million and $<ix:nonFraction name="us-gaap:ResearchAndDevelopmentExpense" id="Fact_f19630c62fc04ac590d8f34e449d0135" contextRef="c20180101to20181231_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsMember" unitRef="U001" decimals="-5" scale="6" format="ixt:numdotdecimal">58.7</ix:nonFraction> million, respectively, were related to our partner agreements.</div>
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<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">F-<span>16</span></div>
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<div 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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</ix:continuation><ix:nonNumeric name="us-gaap:IntangibleAssetsFiniteLivedPolicy" id="Text_4ba9c595a228410fb80294db6e9e8808" contextRef="c20200101to20201231" escape="true" continuedAt="Text_4a8c4ff19350496195f5e54a3da68ea41"><ix:continuation id="Text_87be9d1f99044181a322729aef922491217" continuedAt="Text_87be9d1f99044181a322729aef922491218">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We capitalize costs consisting principally of outside legal costs and filing fees related to obtaining patents. We amortize patent costs over the useful life of the patent, beginning with the date the U.S. Patent and Trademark Office, or foreign equivalent, issues the patent. The weighted average remaining amortizable life of our issued patents was <ix:nonNumeric name="us-gaap:FiniteLivedIntangibleAssetUsefulLife" id="Fact_0743de364414479fa413c5d659ce3213" contextRef="c20200101to20201231_FiniteLivedIntangibleAssetsByMajorClassAxis_PatentsMember" format="ixt-sec:duryear">10.3</ix:nonNumeric> years at December 31, 2020.</div>
</ix:continuation></ix:nonNumeric><ix:continuation id="Text_4a8c4ff19350496195f5e54a3da68ea41" continuedAt="Text_4a8c4ff19350496195f5e54a3da68ea42"><ix:continuation id="Text_87be9d1f99044181a322729aef922491218" continuedAt="Text_87be9d1f99044181a322729aef922491219">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_4a8c4ff19350496195f5e54a3da68ea42" continuedAt="Text_4a8c4ff19350496195f5e54a3da68ea43"><ix:continuation id="Text_87be9d1f99044181a322729aef922491219" continuedAt="Text_87be9d1f99044181a322729aef922491220">
<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 cost of our patents capitalized on our consolidated balance sheet at December 31, 2020 and 2019 was $<ix:nonFraction name="us-gaap:FiniteLivedIntangibleAssetsGross" id="Fact_df1e6fe595054242bd56601d34e950e2" contextRef="c20201231_FiniteLivedIntangibleAssetsByMajorClassAxis_PatentsMember" unitRef="U001" decimals="-5" scale="6" format="ixt:numdotdecimal">37.0</ix:nonFraction> million and $<ix:nonFraction name="us-gaap:FiniteLivedIntangibleAssetsGross" id="Fact_421e79a98335467eb99a9cba6857377d" contextRef="c20191231_FiniteLivedIntangibleAssetsByMajorClassAxis_PatentsMember" unitRef="U001" decimals="-5" scale="6" format="ixt:numdotdecimal">34.0</ix:nonFraction> million, respectively. Accumulated amortization related to patents was $<ix:nonFraction name="us-gaap:FiniteLivedIntangibleAssetsAccumulatedAmortization" id="Fact_414dd9c96ebb45a28f493a17da9dec2e" contextRef="c20201231_FiniteLivedIntangibleAssetsByMajorClassAxis_PatentsMember" unitRef="U001" decimals="-5" scale="6" format="ixt:numdotdecimal">9.1</ix:nonFraction> million and $<ix:nonFraction name="us-gaap:FiniteLivedIntangibleAssetsAccumulatedAmortization" id="Fact_91380e7cfc944a1e8053aef43d6d897f" contextRef="c20191231_FiniteLivedIntangibleAssetsByMajorClassAxis_PatentsMember" unitRef="U001" decimals="-5" scale="6" format="ixt:numdotdecimal">8.3</ix:nonFraction> million at December 31, 2020 and 2019, respectively.</div>
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</ix:continuation></ix:continuation><ix:nonNumeric name="us-gaap:ScheduleofFiniteLivedIntangibleAssetsFutureAmortizationExpenseTableTextBlock" id="Text_94528c9584664d73b67412f9d345feef" contextRef="c20200101to20201231" escape="true" continuedAt="Text_6b22e78bb3a1458ab66cebc4d94f2b791"><ix:continuation id="Text_4a8c4ff19350496195f5e54a3da68ea44" continuedAt="Text_4a8c4ff19350496195f5e54a3da68ea45"><ix:continuation id="Text_87be9d1f99044181a322729aef922491221" continuedAt="Text_87be9d1f99044181a322729aef922491222">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Based on our existing patents, we estimate amortization expense related to patents in each of the next five years to be the following:</div>
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</ix:continuation></ix:continuation></ix:continuation><ix:continuation id="Text_6b22e78bb3a1458ab66cebc4d94f2b792"><ix:continuation id="Text_4a8c4ff19350496195f5e54a3da68ea46" continuedAt="Text_4a8c4ff19350496195f5e54a3da68ea47"><ix:continuation id="Text_87be9d1f99044181a322729aef922491223" continuedAt="Text_87be9d1f99044181a322729aef922491224">
<table cellpadding="0" cellspacing="0" id="z1566f0aad503425294fc597dc5e10f73" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Year Ending December 31,</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Amortization</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(in millions)</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#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;">2021</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:FiniteLivedIntangibleAssetsAmortizationExpenseNextTwelveMonths" id="Fact_8b4595506d5b46448ab97fdee1240d0f" contextRef="c20201231_FiniteLivedIntangibleAssetsByMajorClassAxis_PatentsMember" unitRef="U001" decimals="-5" scale="6" format="ixt:numdotdecimal">2.1</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#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;">2022</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:FiniteLivedIntangibleAssetsAmortizationExpenseYearTwo" id="Fact_e44494ea589f4fd6bf584443ca16bfcc" contextRef="c20201231_FiniteLivedIntangibleAssetsByMajorClassAxis_PatentsMember" unitRef="U001" decimals="-5" scale="6" format="ixt:numdotdecimal">2.0</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2023</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:FiniteLivedIntangibleAssetsAmortizationExpenseYearThree" id="Fact_5f35096f0bcf43fb92b147de0bf72462" contextRef="c20201231_FiniteLivedIntangibleAssetsByMajorClassAxis_PatentsMember" unitRef="U001" decimals="-5" scale="6" format="ixt:numdotdecimal">1.9</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#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;">2024</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:FiniteLivedIntangibleAssetsAmortizationExpenseYearFour" id="Fact_7b3245e6bc5b4426819c1fb6dc13148c" contextRef="c20201231_FiniteLivedIntangibleAssetsByMajorClassAxis_PatentsMember" unitRef="U001" decimals="-5" scale="6" format="ixt:numdotdecimal">1.7</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2025</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:FiniteLivedIntangibleAssetsAmortizationExpenseYearFive" id="Fact_f350bd894a8d412c8d2a916536e277ef" contextRef="c20201231_FiniteLivedIntangibleAssetsByMajorClassAxis_PatentsMember" unitRef="U001" decimals="-5" scale="6" format="ixt:numdotdecimal">1.6</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
</table>
</ix:continuation></ix:continuation></ix:continuation><ix:continuation id="Text_4a8c4ff19350496195f5e54a3da68ea47" continuedAt="Text_4a8c4ff19350496195f5e54a3da68ea48"><ix:continuation id="Text_87be9d1f99044181a322729aef922491224" continuedAt="Text_87be9d1f99044181a322729aef922491225">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_87be9d1f99044181a322729aef922491225" continuedAt="Text_87be9d1f99044181a322729aef922491226"><ix:continuation id="Text_4a8c4ff19350496195f5e54a3da68ea48">
<div 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 capitalized patent costs regularly to ensure that they include costs for patents and patent applications that have future value. When we identify patents and patent applications that we are not actively pursuing, we write off any associated costs. In 2020, 2019 and 2018, patent expenses were $<ix:nonFraction name="us-gaap:ResearchAndDevelopmentExpense" id="Fact_49b21994e36f479d8fb8491e6b0e2bec" contextRef="c20200101to20201231_FiniteLivedIntangibleAssetsByMajorClassAxis_PatentsMember" unitRef="U001" decimals="-5" scale="6" format="ixt:numdotdecimal">4.1</ix:nonFraction> million, $<ix:nonFraction name="us-gaap:ResearchAndDevelopmentExpense" id="Fact_9907ec92e4dd4419b5a9f4fb46f56330" contextRef="c20190101to20191231_FiniteLivedIntangibleAssetsByMajorClassAxis_PatentsMember" unitRef="U001" decimals="-5" scale="6" format="ixt:numdotdecimal">4.2</ix:nonFraction> million and $<ix:nonFraction name="us-gaap:ResearchAndDevelopmentExpense" id="Fact_3201b72effcf4c0c8e0d51523e32d64f" contextRef="c20180101to20181231_FiniteLivedIntangibleAssetsByMajorClassAxis_PatentsMember" unitRef="U001" decimals="-5" scale="6" format="ixt:numdotdecimal">2.6</ix:nonFraction> million, respectively, and included non-cash charges related to the write-down of our patent costs to their estimated net realizable values of $<ix:nonFraction name="us-gaap:ImpairmentOfIntangibleAssetsFinitelived" id="Fact_acdbb50a6f92446b87e379e817f900c3" contextRef="c20200101to20201231_FiniteLivedIntangibleAssetsByMajorClassAxis_PatentsMember" unitRef="U001" decimals="-5" scale="6" format="ixt:numdotdecimal">1.9</ix:nonFraction> million, $<ix:nonFraction name="us-gaap:ImpairmentOfIntangibleAssetsFinitelived" id="Fact_3029299725d54805be6165d35d2050b9" contextRef="c20190101to20191231_FiniteLivedIntangibleAssetsByMajorClassAxis_PatentsMember" unitRef="U001" decimals="-5" scale="6" format="ixt:numdotdecimal">2.2</ix:nonFraction> million and $<ix:nonFraction name="us-gaap:ImpairmentOfIntangibleAssetsFinitelived" id="Fact_1057b62f0867480b862004e4e8b9e9ed" contextRef="c20180101to20181231_FiniteLivedIntangibleAssetsByMajorClassAxis_PatentsMember" unitRef="U001" decimals="-5" scale="6" format="ixt:numdotdecimal">0.8</ix:nonFraction> million, respectively.</div>
</ix:continuation></ix:continuation><ix:continuation id="Text_87be9d1f99044181a322729aef922491226" continuedAt="Text_87be9d1f99044181a322729aef922491227">
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</ix:continuation><ix:continuation id="Text_87be9d1f99044181a322729aef922491227" continuedAt="Text_87be9d1f99044181a322729aef922491228">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Accrued Liabilities</div>
</ix:continuation><ix:continuation id="Text_87be9d1f99044181a322729aef922491228" continuedAt="Text_87be9d1f99044181a322729aef922491229">
<div><br /></div>
</ix:continuation><ix:nonNumeric name="us-gaap:ScheduleOfAccruedLiabilitiesTableTextBlock" id="Text_dee06e4770204682af8c0b46599d481a" contextRef="c20200101to20201231" escape="true" continuedAt="Text_6096512faf0c47eebffc2375951f50e71"><ix:continuation id="Text_87be9d1f99044181a322729aef922491229" continuedAt="Text_87be9d1f99044181a322729aef922491230">
<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:continuation></ix:nonNumeric><ix:continuation id="Text_6096512faf0c47eebffc2375951f50e71" continuedAt="Text_6096512faf0c47eebffc2375951f50e72"><ix:continuation id="Text_87be9d1f99044181a322729aef922491230" continuedAt="Text_87be9d1f99044181a322729aef922491231">
<div><br /></div>
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<table cellpadding="0" cellspacing="0" id="zc442150657ce4320af53f69853dbac04" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"></div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="6" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><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" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2020</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2019</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Noncontrolling Interest in Akcea Therapeutics, Inc.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Since Akcea&#8217;s IPO in July 2017 and prior to the Akcea Acquisition in October 2020, the shares of Akcea&#8217;s common stock third parties owned represented an interest in Akcea&#8217;s equity that we did not control. During this period our ownership ranged from </span><ix:nonFraction name="us-gaap:MinorityInterestOwnershipPercentageByParent" id="Fact_1097de361427408da42d756b10b489be" contextRef="c20201031_OwnershipAxis_AkceaTherapeuticsIncMember_RangeAxis_MinimumMember" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">68</ix:nonFraction> percent<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> to </span><ix:nonFraction name="us-gaap:MinorityInterestOwnershipPercentageByParent" id="Fact_5665dba820d74eba9e6f5307d4168e81" contextRef="c20201031_OwnershipAxis_AkceaTherapeuticsIncMember_RangeAxis_MaximumMember" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">77</ix:nonFraction> percent<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. However, as we maintained overall control of Akcea through our voting interest, we reflected the assets, liabilities and results of operations of Akcea in our consolidated financial statements. Since Akcea&#8217;s IPO in July 2017 and through the closing of the Akcea Acquisition, we reflected the noncontrolling interest attributable to other owners of Akcea&#8217;s common stock on a separate line on our statement of operations and a separate line within stockholders&#8217; equity in our consolidated balance sheet. In addition, through the closing of the Akcea Acquisition, we recorded a noncontrolling interest adjustment to account for the stock options Akcea granted, which if exercised, would have diluted our ownership in Akcea. This adjustment was a reclassification within stockholders&#8217; equity from additional paid-in capital to noncontrolling interest in Akcea equal to the amount of stock-based compensation expense Akcea had recognized. Additionally, w</span>e reflected changes in our ownership percentage in our financial statements as an adjustment to noncontrolling interest in the period the change occurred.</div>
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<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">F-<span>17</span></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 style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Cash, Cash Equivalents and Investments</div>
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<div 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 statement of operations. We use the specific identification method to determine the cost of securities sold.</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 have equity investments of less than 20 percent ownership in publicly and privately held biotechnology companies that we received as part of a technology license or partner agreement. At December 31, 2020, we held equity investments in <ix:nonFraction name="ions:NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment" id="Fact_b448547c88c7434cbc329f97a4b3ea28" contextRef="c20201231" unitRef="U007" decimals="INF" scale="0" format="ixt-sec:numwordsen">two</ix:nonFraction> publicly held companies, ProQR Therapeutics N.V., or ProQR, and Antisense Therapeutics Limited, or ATL. We also held equity investments in <ix:nonFraction name="ions:NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment" id="Fact_5091e6339b9e4e85943dd42b9d332383" contextRef="c20201231" unitRef="U007" decimals="INF" scale="0" format="ixt-sec:numwordsen">seven</ix:nonFraction> privately-held companies, Aro Biotherapeutics, Atlantic Pharmaceuticals Limited, Dynacure SAS, Empirico, Inc., Flamingo Therapeutics BV, Seventh Sense Biosystems and Suzhou-Ribo Life Science Co, Ltd.</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 required to measure and record our equity investments at fair value and to recognize the changes in fair value in our consolidated statement of operations. We account for our equity investments in privately held companies at their cost minus impairments, plus or minus changes resulting from observable price changes in orderly transactions for the identical or similar investment of the same issuer. For example, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">during the second and fourth quarters of 2020, we revalued our investments in </span><ix:nonFraction name="ions:NumberOfInvestmentsInPrivatelyHeldCompaniesThatWereRevalued" id="Fact_f7fa3e5a04194e26a2205eb8715ec05c" contextRef="c20200401to20201231" unitRef="U008" decimals="INF" scale="0" format="ixt-sec:numwordsen">three</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> privately held companies, Dynacure, Suzhou-Ribo and Aro Biotherapeutics because the companies sold additional equity securities that were similar to the equity we own. These observable price changes resulted in us recognizing a $</span><ix:nonFraction name="us-gaap:GainLossOnInvestments" id="Fact_cdc5aa89677e4989aa728a9bb2e0edf9" contextRef="c20200401to20200630_FinancialInstrumentAxis_DynacureSasMember" unitRef="U001" decimals="-5" scale="6" format="ixt:numdotdecimal">6.3</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million gain on our investment in Dynacure, a $</span><ix:nonFraction name="us-gaap:GainLossOnInvestments" id="Fact_47b16f5d19a84a8c9a09fbbe96174527" contextRef="c20201001to20201231_FinancialInstrumentAxis_SuzhouRiboLifeScienceCoLtdMember" unitRef="U001" decimals="-5" scale="6" format="ixt:numdotdecimal">3.0</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million gain on our investment in Suzhou-Ribo and a $</span><ix:nonFraction name="us-gaap:GainLossOnInvestments" id="Fact_cf49d586d5334999834bf4a673cb3dfa" contextRef="c20201001to20201231_FinancialInstrumentAxis_AroBiotherapeuticsMember" unitRef="U001" decimals="-5" scale="6" format="ixt:numdotdecimal">5.5</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million gain on our investment in Aro Biotherapeutics in our consolidated statement of operations during 2020 because the sales were at higher prices compared to our recorded value.</span></div>
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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Inventory Valuation</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We reflect our inventory on our consolidated balance sheet 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.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We obtained the first regulatory approval for TEGSEDI in July 2018 and for WAYLIVRA in May 2019. At December 31, 2020, our physical inventory for TEGSEDI and WAYLIVRA included API that we produced prior to when we obtained regulatory approval. As such, this API has no cost basis as we had previously expensed the costs as R&amp;D expenses.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We 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. We recorded an <span style="-sec-ix-hidden:Fact_b86d72920caa47448f2abd7be8e5c180"><span style="-sec-ix-hidden:Fact_1261d93c836d4d94bba4bd8c45f1e569">insignificant</span></span> amount of inventory write-offs during the years ended December 31, 2020 and 2019. We did <ix:nonFraction name="us-gaap:InventoryWriteDown" id="Fact_4bf69ae4679448c7a37b15f378b51ee0" contextRef="c20180101to20181231" unitRef="U001" decimals="-3" scale="3" format="ixt-sec:numwordsen">no</ix:nonFraction>t record any inventory write-offs for the year ended December 31, 2018.</div>
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<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">F-<span>18</span></div>
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<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 colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Property, Plant and Equipment</div>
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<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We carry our property, plant and equipment at cost and depreciate it on the straight-line method over its estimated useful life, which consists of the following (in thousands):</div>
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    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
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  <tr>
    <td valign="bottom" style="vertical-align: bottom; background-color: #CCEEFF;"><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>
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  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:PropertyPlantAndEquipmentGross" id="Fact_36283464a0474949b8398ef74fa87f78" contextRef="c20201231_PropertyPlantAndEquipmentByTypeAxis_BuildingAndBuildingImprovementsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">137,879</ix:nonFraction></div></td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom;">&#160;</td>
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  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonNumeric name="us-gaap:PropertyPlantAndEquipmentUsefulLife" id="Fact_c74c578c9a114415ba62e9a933b22bc1" contextRef="c20200101to20201231_PropertyPlantAndEquipmentByTypeAxis_LandImprovementsMember" format="ixt-sec:duryear">20</ix:nonNumeric></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:PropertyPlantAndEquipmentGross" id="Fact_9274143ded5b4f0ba33136edf1a5c107" contextRef="c20201231_PropertyPlantAndEquipmentByTypeAxis_LeaseholdImprovementsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">17,263</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>
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  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:PropertyPlantAndEquipmentGross" id="Fact_4cc9147a7cbc4ee49795347f0fb5a079" contextRef="c20201231_PropertyPlantAndEquipmentByTypeAxis_FurnitureAndFixturesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">12,871</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:PropertyPlantAndEquipmentGross" id="Fact_94b40916e0474421a05f751c4a6948c3" contextRef="c20191231_PropertyPlantAndEquipmentByTypeAxis_FurnitureAndFixturesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">7,354</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 64%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#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;">Less accumulated depreciation</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:PropertyPlantAndEquipmentNet" id="Fact_c1ac0d6f145b41659e8c734c98f6f1c8" contextRef="c20191231" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">153,651</ix:nonFraction></div></td>
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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 depreciate our leasehold improvements using the shorter of the estimated useful life or remaining lease term.</div>
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</ix:continuation><ix:nonNumeric name="us-gaap:FairValueOfFinancialInstrumentsPolicy" id="Text_1c1a3fa5b06c4f8eb0d08a8a2d8e1c26" contextRef="c20200101to20201231" escape="true" continuedAt="Text_a492c48c396f4de9b10e642fd64fd9901"><ix:continuation id="Text_87be9d1f99044181a322729aef922491269" continuedAt="Text_87be9d1f99044181a322729aef922491270">
<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Fair Value of Financial Instruments</div>
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<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> </span><br /></div>
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<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We have estimated the fair value of our financial instruments. The amounts reported for cash, accounts receivable, accounts payable and accrued expenses approximate the fair value because of their short maturities. We report our investment securities at their estimated fair value based on quoted market prices for identical or similar instruments.</div>
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<div><br /></div>
</ix:continuation><ix:nonNumeric name="us-gaap:LesseeLeasesPolicyTextBlock" id="Text_5a1cbe260fe343ccafe9ff400e9af2db" contextRef="c20200101to20201231" escape="true" continuedAt="Text_bcb1e8576535478f876e96e256fbdf691"><ix:continuation id="Text_87be9d1f99044181a322729aef922491273" continuedAt="Text_87be9d1f99044181a322729aef922491274">
<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><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 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 on our consolidated balance sheet 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;">&#xA0;</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 concluded we were reasonably certain that we will 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><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 our current leases do not provide an interest rate implicit in the lease, we used our incremental borrowing rate, based on the information available on the date we adopted Topic 842 (January 2019), 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. We recognize period expenses, such as common area maintenance expenses, in the period we incur the expense.</div>
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<div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">F-<span>19</span></div>
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</div>
<div><ix:nonNumeric name="us-gaap:ImpairmentOrDisposalOfLongLivedAssetsIncludingIntangibleAssetsPolicyPolicyTextBlock" id="Text_72f861d09ee741518162baaf74392e58" contextRef="c20200101to20201231" escape="true" continuedAt="Text_17002e49d5e04a15a0f17725ca88e8cb1"><ix:continuation id="Text_87be9d1f99044181a322729aef922491279" continuedAt="Text_87be9d1f99044181a322729aef922491280">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Long-Lived Assets</div>
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<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> </span><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_87be9d1f99044181a322729aef922491281" continuedAt="Text_87be9d1f99044181a322729aef922491282"><ix:continuation id="Text_17002e49d5e04a15a0f17725ca88e8cb2">
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We evaluate long-lived assets, which include property, plant and equipment and patent costs, 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. We recorded charges of $<ix:nonFraction name="us-gaap:ImpairmentOfIntangibleAssetsFinitelived" id="Fact_1f00325938654d8aaa92961967dd4fe1" contextRef="c20200101to20201231" unitRef="U001" decimals="-5" scale="6" format="ixt:numdotdecimal">1.9</ix:nonFraction> million, $<ix:nonFraction name="us-gaap:ImpairmentOfIntangibleAssetsFinitelived" id="Fact_d4bb9e72c83944a891eb6db91aae4474" contextRef="c20190101to20191231" unitRef="U001" decimals="-5" scale="6" format="ixt:numdotdecimal">2.2</ix:nonFraction> million and $<ix:nonFraction name="us-gaap:ImpairmentOfIntangibleAssetsFinitelived" id="Fact_42a5e2e524a746bebd539b59be5602e1" contextRef="c20180101to20181231" unitRef="U001" decimals="-5" scale="6" format="ixt:numdotdecimal">0.8</ix:nonFraction> million for the years ended December 31, 2020, 2019 and 2018, respectively, related to the write-down of patents.</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;">Use of Estimates</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The preparation of consolidated financial statements in conformity with accounting principles generally accepted in the U.S. requires management to make estimates and assumptions that affect the amounts reported in the consolidated financial statements and accompanying notes. Actual results could differ from those estimates.</div>
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<div><br /></div>
</ix:continuation><ix:nonNumeric name="us-gaap:ShareBasedCompensationOptionAndIncentivePlansPolicy" id="Text_ad082f24466d4b628f8d68f86e583d6f" contextRef="c20200101to20201231" escape="true" continuedAt="Text_ba7fbdb672b54ba2a0a7d27b7c7f9cc31"><ix:continuation id="Text_87be9d1f99044181a322729aef922491287" continuedAt="Text_87be9d1f99044181a322729aef922491288">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Stock-Based Compensation Expense</div>
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<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_ba7fbdb672b54ba2a0a7d27b7c7f9cc32" continuedAt="Text_ba7fbdb672b54ba2a0a7d27b7c7f9cc33"><ix:continuation id="Text_87be9d1f99044181a322729aef922491289" continuedAt="Text_87be9d1f99044181a322729aef922491290">
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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, and stock purchase rights under our ESPP based on the estimated fair value of the award on the date of grant. We recognize the value of the portion of the award that we ultimately expect to vest as stock-based compensation expense over the requisite service period in our consolidated statements of operations. We reduce stock-based compensation expense for estimated forfeitures at the time of grant and revise in subsequent periods if actual forfeitures differ from those estimates.</div>
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<div><br /></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. We estimate the expected term of options granted based on 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;">We recognize compensation expense for option awards and RSUs 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;">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 vest annually over a <ix:nonNumeric name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1" id="Fact_9c07a9a996a942cfa5196c4e73d65a5f" contextRef="c20200101to20201231_AwardTypeAxis_RestrictedStockUnitsRSUMember" format="ixt-sec:durwordsen">four-year</ix:nonNumeric> period. RSUs granted after June 2020 to our board of directors vest annually.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">See Note 4, <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: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Accumulated other comprehensive loss is comprised of unrealized gains and losses on investments, net of taxes and currency translation adjustments. The following table summarizes changes in accumulated other comprehensive loss for the years ended December 31, </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">2020</span><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;">2019</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> and </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">2018</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> (in thousands):</span></div>
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<div style="text-align: justify;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> </span><br /></div>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherComprehensiveIncomeLossNetOfTax" id="Fact_a2223b8bb7e44f6f89e44f7a99d65ec1" contextRef="c20190101to20191231" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">6,726</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:OtherComprehensiveIncomeLossNetOfTax" id="Fact_15d14efe39a949dabe720e0cc4f8a8d2" contextRef="c20180101to20181231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">257</ix:nonFraction></div></td>
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  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" id="Fact_47d26dc5eb544c51b35c31726e80cf7c" contextRef="c20201231_StatementEquityComponentsAxis_AociIncludingPortionAttributableToNoncontrollingInterestMember" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">21,071</ix:nonFraction></div></td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" id="Fact_92c6a81d4cc548c79c16aa702d293bfc" contextRef="c20191231_StatementEquityComponentsAxis_AociIncludingPortionAttributableToNoncontrollingInterestMember" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">25,290</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" id="Fact_d50f6f2316fb42a59ada44dcc1e3f6fc" contextRef="c20181231_StatementEquityComponentsAxis_AociIncludingPortionAttributableToNoncontrollingInterestMember" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">32,016</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
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<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="z9ecfa3f5cf504526a0786f25593849bf">
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    <td style="width: 18pt; vertical-align: top; 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; text-indent: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:footnote id="Foot_c173053f21eb48f2baac71e2bf36f606" footnoteRole="http://www.xbrl.org/2003/role/footnote" xml:lang="en-US" continuedAt="Foot_f579fd2f872540de8ec1b9de052c5d4f1">We did <ix:nonFraction name="us-gaap:OtherComprehensiveIncomeLossTax" id="Fact_51731348898e477f98ddd1af36189c22" contextRef="c20200101to20201231" unitRef="U001" decimals="-6" scale="6" format="ixt-sec:numwordsen">no</ix:nonFraction></ix:footnote><ix:continuation id="Foot_f579fd2f872540de8ec1b9de052c5d4f1" continuedAt="Foot_f579fd2f872540de8ec1b9de052c5d4f2">t have tax expense included in our other comprehensive loss for the year ended December 31, 2020. For the years ended December 31, 2019</ix:continuation><ix:continuation id="Foot_f579fd2f872540de8ec1b9de052c5d4f2" continuedAt="Foot_f579fd2f872540de8ec1b9de052c5d4f3"> and 2018</ix:continuation><ix:continuation id="Foot_f579fd2f872540de8ec1b9de052c5d4f3" continuedAt="Foot_f579fd2f872540de8ec1b9de052c5d4f4">, we had a tax benefit $<ix:nonFraction name="us-gaap:OtherComprehensiveIncomeLossTax" id="Fact_b4c227fd58254a14b4a1aab9ae5a2738" contextRef="c20190101to20191231" unitRef="U001" decimals="-5" scale="6" sign="-" format="ixt:numdotdecimal">1.4</ix:nonFraction></ix:continuation><ix:continuation id="Foot_f579fd2f872540de8ec1b9de052c5d4f4" continuedAt="Foot_f579fd2f872540de8ec1b9de052c5d4f5"> million and $<ix:nonFraction name="us-gaap:OtherComprehensiveIncomeLossTax" id="Fact_5760e35e9cbb4b309eabc1063cb761ae" contextRef="c20180101to20181231" unitRef="U001" decimals="-5" scale="6" sign="-" format="ixt:numdotdecimal">0.3</ix:nonFraction></ix:continuation><ix:continuation id="Foot_f579fd2f872540de8ec1b9de052c5d4f5"> million included in other comprehensive loss respectively.</ix:continuation>&#xA0;</div></td>
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<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">F-<span>20</span></div>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Convertible Debt</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">At issuance, we accounted for our convertible debt instruments, including our <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_9dac22281bdf451a940008eda1d7a823" contextRef="c20201231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:numdotdecimal">0.125</ix:nonFraction> percent senior convertible notes, or <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_21cdbefcddab46039805db2aaa0c4339" contextRef="c20201231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:numdotdecimal">0.125</ix:nonFraction>% Notes, and <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_d2044d977d4a415c9cadeaa7e187ed54" contextRef="c20201231_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">1</ix:nonFraction> percent senior convertible notes, or <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_b10b14bf0679415f909b7c584e5b9db5" contextRef="c20201231_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">1</ix:nonFraction>% Notes, that may be settled in cash upon conversion (including partial cash settlement) by separating the liability and equity components of the instruments in a manner that reflects our nonconvertible debt borrowing rate on the date the notes were issued. In reviewing debt issuances, we were not able to identify any comparable companies that issued non-convertible debt instruments at the time of the issuance of the convertible notes. Therefore, we estimated the fair value of the liability component of our notes by using assumptions that market participants would use in pricing a debt instrument, including market interest rates, credit standing, yield curves and volatilities.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We assigned a value to the debt component of our convertible notes equal to the estimated fair value of similar debt instruments without the conversion feature, which resulted in us recording our debt at a discount. We are amortizing our debt issuance costs and debt discount over the life of the convertible notes as additional non-cash interest expense utilizing the effective interest method. For additional information, see Note 3, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Long-Term Obligations and Commitments</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 <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_05115194168e46d093b42c51cd859209" contextRef="c20201231_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">1</ix:nonFraction>% Notes mature in November 2021. Therefore, as of December 31, 2020, we classified the liability component of the <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_1c29e084ec014e05bd5b43e43093e149" contextRef="c20201231_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">1</ix:nonFraction>% Notes as a current liability on our consolidated balance sheet.</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 2020, the FASB issued guidance simplifying the accounting for convertible debt instruments. See the section titled &#8220;Impact of Recently Issued Accounting Standards&#8221; below for details.</div>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Call Spread</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In conjunction with the issuance of our <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_c7389f24076f455d9829308572fe948e" contextRef="c20201231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:numdotdecimal">0.125</ix:nonFraction>% Notes, we entered into a call spread transaction, which was 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 Derivatives and Hedging &#8211; Contracts in Entity&#8217;s Own Equity 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 sheet. We reassess our ability to continue to classify the note hedges and warrants in shareholders&#8217; equity at each reporting period.</div>
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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Segment Information</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Through 2020, we had <ix:nonFraction name="us-gaap:NumberOfOperatingSegments" id="Fact_419f6aaf7f954198a58ab39bfb5080c8" contextRef="c20200101to20201231" unitRef="U009" decimals="INF" scale="0" format="ixt-sec:numwordsen">two</ix:nonFraction> operating segments, our Ionis Core segment and Akcea Therapeutics. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Akcea was focused on developing and commercializing medicines to treat patients with serious and rare diseases. We have provided segment financial information and results for our Ionis Core segment and our Akcea Therapeutics segment based on the segregation of revenues and expenses that our chief decision maker reviewed to assess operating performance and to make operating decisions through 2020. We allocated a portion of Ionis&#8217; development, R&amp;D support and general and administrative expenses to Akcea for work Ionis performed on behalf of Akcea and we billed Akcea for these expenses.</span></div>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Fair Value Measurements</div>
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<div style="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 held 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 style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">F-<span>21</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 following tables present the major security types we held at December 31, 2020 and 2019&#xA0;<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">that we regularly measure and carry at fair value</span>. At December 31, 2019, our ProQR investment was <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">subject to trading restrictions until the fourth quarter of 2020, as a result we</span> included a lack of marketability discount in valuing this investment, which is a Level 3 input. As of December 31, 2020, our ProQR investment was no longer subject to trading restrictions. As of December 31, 2020, we did not have any investments which we valued using Level 3 inputs. The following tables segregate each security type by the level within the fair value hierarchy of the valuation techniques we utilized to determine the respective securities&#8217; fair value (in thousands):</div>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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  <tr>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
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  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#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 (4)</div></div></td>
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<div><br /></div>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
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  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by states of the U.S. and political subdivisions of the states (4)</div></td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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  <tr>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:EquitySecuritiesFvNi" id="Fact_cd8848724d3a4b7c8f698a98cfad6ef8" contextRef="c20191231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember" unitRef="U001" decimals="-3" scale="3" format="ixt:zerodash">&#8212;</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:EquitySecuritiesFvNi" id="Fact_51a776a3c3724c5da2107bd7882086d5" contextRef="c20191231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember" unitRef="U001" decimals="-3" scale="3" format="ixt:zerodash">&#8212;</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:EquitySecuritiesFvNi" id="Fact_0e5d97a4f5634458a86e73a8df42af50" contextRef="c20191231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel3Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">4,506</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
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    <td valign="bottom" style="vertical-align: bottom; width: 52%; 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>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AssetsFairValueDisclosure" id="Fact_dc11b10a350e43f09509ec7adfbe3fb1" contextRef="c20191231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">1,472,379</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AssetsFairValueDisclosure" id="Fact_efc7bd319e6048baa4c12bac36ead8a2" contextRef="c20191231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel3Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">4,506</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
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</ix:continuation></ix:continuation></ix:continuation><ix:continuation id="Text_253b34bbe91742448d332de149b0e98b5" continuedAt="Text_253b34bbe91742448d332de149b0e98b6"><ix:continuation id="Text_750018c4c23d46de889e5cdd45b638f79" continuedAt="Text_750018c4c23d46de889e5cdd45b638f710"><ix:continuation id="Text_87be9d1f99044181a322729aef922491334" continuedAt="Text_87be9d1f99044181a322729aef922491335">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">________________</div>
</ix:continuation></ix:continuation></ix:continuation><ix:continuation id="Text_253b34bbe91742448d332de149b0e98b6" continuedAt="Text_253b34bbe91742448d332de149b0e98b7"><ix:continuation id="Text_750018c4c23d46de889e5cdd45b638f710" continuedAt="Text_750018c4c23d46de889e5cdd45b638f711"><ix:continuation id="Text_87be9d1f99044181a322729aef922491335" continuedAt="Text_87be9d1f99044181a322729aef922491336">
<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="z791574a09f2444c599172d57b45fe997">
  <tr>
    <td style="width: 36pt; vertical-align: top; align: right; 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 on our consolidated balance sheet.</ix:footnote></div></td>
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</ix:continuation></ix:continuation></ix:continuation><ix:continuation id="Text_253b34bbe91742448d332de149b0e98b7" continuedAt="Text_253b34bbe91742448d332de149b0e98b8"><ix:continuation id="Text_750018c4c23d46de889e5cdd45b638f711" continuedAt="Text_750018c4c23d46de889e5cdd45b638f712"><ix:continuation id="Text_87be9d1f99044181a322729aef922491336" continuedAt="Text_87be9d1f99044181a322729aef922491337">
<div><br /></div>
</ix:continuation></ix:continuation></ix:continuation><ix:continuation id="Text_253b34bbe91742448d332de149b0e98b8" continuedAt="Text_253b34bbe91742448d332de149b0e98b9"><ix:continuation id="Text_750018c4c23d46de889e5cdd45b638f712" continuedAt="Text_750018c4c23d46de889e5cdd45b638f713"><ix:continuation id="Text_87be9d1f99044181a322729aef922491337" continuedAt="Text_87be9d1f99044181a322729aef922491338">
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  <tr>
    <td style="width: 36pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(2)</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:footnote id="Foot_77eb85d4142a44a68a7c6b25a7169d1c" footnoteRole="http://www.xbrl.org/2003/role/footnote" xml:lang="en-US" continuedAt="Foot_360b32d83bdb462eb3566da2b69f8fb01">$<ix:nonFraction name="us-gaap:AvailableForSaleSecurities" id="Fact_ce470ce0da684fc0965a0abdbc5bdb8f" contextRef="c20201231_BalanceSheetLocationAxis_CashAndCashEquivalentsMember_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U001" decimals="-5" scale="6" format="ixt:numdotdecimal">10.0</ix:nonFraction></ix:footnote><ix:continuation id="Foot_360b32d83bdb462eb3566da2b69f8fb01"> million included in cash and cash equivalents on our consolidated balance sheet, with the difference included in short-term investments on our consolidated balance sheet.</ix:continuation></div></td>
  </tr>
</table>
</ix:continuation></ix:continuation></ix:continuation><ix:continuation id="Text_253b34bbe91742448d332de149b0e98b9" continuedAt="Text_253b34bbe91742448d332de149b0e98b10"><ix:continuation id="Text_750018c4c23d46de889e5cdd45b638f713" continuedAt="Text_750018c4c23d46de889e5cdd45b638f714"><ix:continuation id="Text_87be9d1f99044181a322729aef922491338" continuedAt="Text_87be9d1f99044181a322729aef922491339">
<div><br /></div>
</ix:continuation></ix:continuation></ix:continuation><ix:continuation id="Text_253b34bbe91742448d332de149b0e98b10" continuedAt="Text_253b34bbe91742448d332de149b0e98b11"><ix:continuation id="Text_750018c4c23d46de889e5cdd45b638f714" continuedAt="Text_750018c4c23d46de889e5cdd45b638f715"><ix:continuation id="Text_87be9d1f99044181a322729aef922491339" continuedAt="Text_87be9d1f99044181a322729aef922491340">
<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="z148638abbe4544afb1bfb13a3a3df99e">
  <tr>
    <td style="width: 36pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(3)</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:footnote id="Foot_cc6012bb3041434399bdb287399a913a" footnoteRole="http://www.xbrl.org/2003/role/footnote" xml:lang="en-US" continuedAt="Foot_ffa53056ad6b41b798f15f8e418412721">$<ix:nonFraction name="us-gaap:AvailableForSaleSecurities" id="Fact_94f64bff77254ab4850b08f2bbbd1572" contextRef="c20201231_BalanceSheetLocationAxis_CashAndCashEquivalentsMember_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U001" decimals="-5" scale="6" format="ixt:numdotdecimal">17.5</ix:nonFraction></ix:footnote><ix:continuation id="Foot_ffa53056ad6b41b798f15f8e418412721"> million included in cash and cash equivalents on our consolidated balance sheet, with the difference included in short-term investments on our consolidated balance sheet.</ix:continuation></div></td>
  </tr>
</table>
</ix:continuation></ix:continuation></ix:continuation><ix:continuation id="Text_253b34bbe91742448d332de149b0e98b11" continuedAt="Text_253b34bbe91742448d332de149b0e98b12"><ix:continuation id="Text_750018c4c23d46de889e5cdd45b638f715" continuedAt="Text_750018c4c23d46de889e5cdd45b638f716"><ix:continuation id="Text_87be9d1f99044181a322729aef922491340" continuedAt="Text_87be9d1f99044181a322729aef922491341">
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</ix:continuation></ix:continuation></ix:continuation><ix:continuation id="Text_253b34bbe91742448d332de149b0e98b12" continuedAt="Text_253b34bbe91742448d332de149b0e98b13"><ix:continuation id="Text_750018c4c23d46de889e5cdd45b638f716" continuedAt="Text_750018c4c23d46de889e5cdd45b638f717"><ix:continuation id="Text_87be9d1f99044181a322729aef922491341" continuedAt="Text_87be9d1f99044181a322729aef922491342">
<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="zfe5f26749b614dbcb042f4c2f2ba5a12">
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    <td style="width: 36pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(4)</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:footnote id="Foot_f0e1d58ea08e4b55a4c7703dd1e397d3" footnoteRole="http://www.xbrl.org/2003/role/footnote" xml:lang="en-US">Included in short-term investments.</ix:footnote></div></td>
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</ix:continuation></ix:continuation></ix:continuation><ix:continuation id="Text_253b34bbe91742448d332de149b0e98b14" continuedAt="Text_253b34bbe91742448d332de149b0e98b15"><ix:continuation id="Text_750018c4c23d46de889e5cdd45b638f718" continuedAt="Text_750018c4c23d46de889e5cdd45b638f719"><ix:continuation id="Text_87be9d1f99044181a322729aef922491343" continuedAt="Text_87be9d1f99044181a322729aef922491344">
<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="z7c2aa671a6d84170836be6a95eff7f0e">
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    <td style="width: 36pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(5)</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:footnote id="Foot_c498c367d1f949d4a789172bf48c4121" footnoteRole="http://www.xbrl.org/2003/role/footnote" xml:lang="en-US">Included in other current assets on our consolidated balance sheet.</ix:footnote></div></td>
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</ix:continuation></ix:continuation></ix:continuation><ix:continuation id="Text_253b34bbe91742448d332de149b0e98b15" continuedAt="Text_253b34bbe91742448d332de149b0e98b16"><ix:continuation id="Text_750018c4c23d46de889e5cdd45b638f719" continuedAt="Text_750018c4c23d46de889e5cdd45b638f720"><ix:continuation id="Text_87be9d1f99044181a322729aef922491344" continuedAt="Text_87be9d1f99044181a322729aef922491345">
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</ix:continuation></ix:continuation></ix:continuation><ix:continuation id="Text_253b34bbe91742448d332de149b0e98b16" continuedAt="Text_253b34bbe91742448d332de149b0e98b17"><ix:continuation id="Text_750018c4c23d46de889e5cdd45b638f720" continuedAt="Text_750018c4c23d46de889e5cdd45b638f721"><ix:continuation id="Text_87be9d1f99044181a322729aef922491345" continuedAt="Text_87be9d1f99044181a322729aef922491346">
<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="zae152b0de27346b784a63d2fad55dc16">
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    <td style="width: 36pt; vertical-align: top; align: right; 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_7f9ebb5194d04d4294eb3dd811ff49fa" footnoteRole="http://www.xbrl.org/2003/role/footnote" xml:lang="en-US" continuedAt="Foot_e125e6e83aa542fcba2274a63ab88f681">$<ix:nonFraction name="us-gaap:AvailableForSaleSecurities" id="Fact_901bc85a32f541369ef5a8de46f7eb74" contextRef="c20191231_BalanceSheetLocationAxis_CashAndCashEquivalentsMember_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U001" decimals="-5" scale="6" format="ixt:numdotdecimal">19.0</ix:nonFraction></ix:footnote><ix:continuation id="Foot_e125e6e83aa542fcba2274a63ab88f681"> million included in cash and cash equivalents on our consolidated balance sheet, with the difference included in short-term investments on our consolidated balance sheet.</ix:continuation></div></td>
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</ix:continuation></ix:continuation></ix:continuation><ix:continuation id="Text_253b34bbe91742448d332de149b0e98b17" continuedAt="Text_253b34bbe91742448d332de149b0e98b18"><ix:continuation id="Text_750018c4c23d46de889e5cdd45b638f721" continuedAt="Text_750018c4c23d46de889e5cdd45b638f722"><ix:continuation id="Text_87be9d1f99044181a322729aef922491346" continuedAt="Text_87be9d1f99044181a322729aef922491347">
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<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="z13ffd34009fd4d8ea5be9d956bd94c78">
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    <td style="width: 36pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(7)</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_e11deb538669403f9b23668e7ec77e3b" footnoteRole="http://www.xbrl.org/2003/role/footnote" xml:lang="en-US" continuedAt="Foot_f3622db4efe7461383c4214fd68ab65c1">$<ix:nonFraction name="us-gaap:AvailableForSaleSecurities" id="Fact_0be87ae2076b4d75a7c41aba90d2f514" contextRef="c20191231_BalanceSheetLocationAxis_CashAndCashEquivalentsMember_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U001" decimals="-5" scale="6">0.8</ix:nonFraction></ix:footnote><ix:continuation id="Foot_f3622db4efe7461383c4214fd68ab65c1"> million included in cash and cash equivalents on our consolidated balance sheet, with the difference included in short-term investments on our consolidated balance sheet.</ix:continuation>&#160; </div></td>
  </tr>
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<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">F-<span>22</span></div>
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<div><ix:nonNumeric name="us-gaap:IncomeTaxPolicyTextBlock" id="Text_ea1db2e5fbf346468e0ca231e0179de4" contextRef="c20200101to20201231" escape="true" continuedAt="Text_909ff91b54ed4ef788ee9479e35436cd1"><ix:continuation id="Text_87be9d1f99044181a322729aef922491349" continuedAt="Text_87be9d1f99044181a322729aef922491350">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Income Taxes</div>
</ix:continuation></ix:nonNumeric><ix:continuation id="Text_909ff91b54ed4ef788ee9479e35436cd1" continuedAt="Text_909ff91b54ed4ef788ee9479e35436cd2"><ix:continuation id="Text_87be9d1f99044181a322729aef922491350" continuedAt="Text_87be9d1f99044181a322729aef922491351">
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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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<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_909ff91b54ed4ef788ee9479e35436cd4" continuedAt="Text_909ff91b54ed4ef788ee9479e35436cd5"><ix:continuation id="Text_87be9d1f99044181a322729aef922491353" continuedAt="Text_87be9d1f99044181a322729aef922491354">
<div 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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<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, no assurance can be given that the final tax outcome of these matters will not be different from that which is 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 such determination is made.</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 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.<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> 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.</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 do not provide for a U.S. income tax liability and foreign withholding taxes on undistributed foreign earnings of our foreign subsidiaries.</div>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Impact of Recently Issued Accounting Standards</div>
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<div><br /></div>
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<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In June 2016, the FASB issued guidance that changes the measurement of credit losses for most financial assets and certain other instruments. If we have credit losses, this updated guidance requires us to record allowances for these instruments under a new expected credit loss model. This model requires us to estimate the expected credit loss of an instrument over its lifetime, which represents the portion of the amortized cost basis we do not expect to collect. The new guidance requires us to remeasure our allowance in each reporting period we have credit losses. We adopted this new guidance on January 1, 2020. This guidance did not have an impact on our consolidated financial statements.</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 2018, the FASB issued clarifying guidance on how to account for implementation costs related to cloud-servicing arrangements. The guidance states that if these fees qualify to be capitalized and amortized over the service period, they need to be expensed in the same line item as the service expense and recognized in the same balance sheet category. The update can be applied either retrospectively or prospectively to all implementation costs incurred after the date of adoption. We adopted this guidance on January 1, 2020 on a prospective basis. This guidance did not have an impact on our consolidated financial statements.</div>
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<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">F-<span>23</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 November 2018, the FASB issued clarifying guidance of the interaction between the collaboration accounting guidance and the new revenue recognition guidance we adopted on January 1, 2018 (Topic 606). Below is the clarifying guidance and how we implemented it (in italics):</div>
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    <td style="width: 18pt; vertical-align: top; align: right; 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;">When a participant is considered a customer in a collaborative arrangement, all of the associated accounting under Topic 606 should be applied.</div></td>
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    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">&#9679;</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;">We are applying all of the associated accounting under Topic 606 when we determine a participant in a collaborative arrangement is a customer.</div></td>
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    <td style="width: 18pt; vertical-align: top; align: right; 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;">Adds &#8220;unit of account&#8221; concept to collaboration accounting guidance to align with Topic 606. The &#8220;unit of account&#8221; concept is used to determine if revenue is recognized or if a contra expense is recognized from consideration received under a collaboration.</div></td>
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    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">&#9679;</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;">We use the &#8220;unit of account&#8221; concept when we receive consideration under a collaborative arrangement to determine when we recognize revenue or a contra expense.</div></td>
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    <td style="width: 18pt; vertical-align: top; align: right; 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;">The clarifying guidance precludes us from recognizing revenue under Topic 606 when we determine a transaction with a collaborative partner is not a customer and is not directly related to the sales to third parties.</div></td>
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    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">&#9679;</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;">When we conclude a collaboration partner is not a customer and is not directly related to the sales to third parties, we do not recognize revenue for the transaction.</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 adopted this new guidance on January 1, 2020. This guidance did not have any impact on our consolidated financial statements.</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 August 2020, the FASB issued guidance </span>which simplifies the accounting for convertible instruments<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, amends the guidance on derivative scope exceptions for contracts in an entity&#8217;s own equity, and modifies the guidance on diluted earnings per share calculations as a result of these changes. Under our current outstanding convertible debt arrangements, we anticipate the following impacts:</span></div>
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<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="zcbb885b9cab547a1b31cd283712248a2">
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    <td style="width: 36pt; vertical-align: top; align: right; 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;">We will no longer separate our existing convertible debt into liability and equity components. Therefore, we will no longer recognize a debt discount for the value of the conversion option, instead we will record the face value of the convertible debt as a liability on our consolidated balance sheet;</div></td>
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<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="z66fb90d1a5be4351bc55d49e62d382d6">
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    <td style="width: 18pt; vertical-align: top; align: right; 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;">We will record cash interest expense plus amortization of debt issuance costs to interest expense. Since we will not recognize a debt discount, we will no longer record the amortization of a debt discount to interest expense; and</div></td>
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<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="ze1e1f5e6552b4bfc822ec7f94c42c685">
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    <td style="width: 18pt; vertical-align: top; align: right; 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;">We do not expect our EPS calculation to not change under this update. We plan to continue to use the if-converted method to calculate diluted earnings per share.</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 plan to adopt this guidance in the first quarter of 2021 under the full retrospective approach, meaning we will apply the guidance to all periods presented beginning in the first quarter of 2021.</div>
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<div><ix:nonNumeric name="us-gaap:InvestmentTextBlock" id="Text_9571e0c61df44815a452af9dc71349ef" contextRef="c20200101to20201231" escape="true" continuedAt="Text_b9c7b283940c4cd6a2a40792997c39f61">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2. Investments</div>
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<div 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, 2020:</div>
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<table cellpadding="0" cellspacing="0" id="zb8b331d548474cfd89ae511966ada4d1" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <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;"><ix:nonNumeric name="ions:MaximumContractMaturityPeriodRange1" id="Fact_a0389bbbc04d444aa9945a16f2f77b47" contextRef="c20200101to20201231" format="ixt-sec:durwordsen">One year</ix:nonNumeric> or less</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage" id="Fact_e1a84f7ba1234915827448c633c10e96" contextRef="c20201231" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">73</ix:nonFraction></div></td>
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    <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 <ix:nonNumeric name="ions:MaximumContractMaturityPeriodRange1" id="Fact_a9a809b245674eb5912c14df728dc0f0" contextRef="c20200101to20201231" format="ixt-sec:durwordsen">one year</ix:nonNumeric> but within <ix:nonNumeric name="ions:MaximumContractMaturityPeriodRange2" id="Fact_d1dd3aa1c3444cc8babea1f02c42cb74" contextRef="c20200101to20201231" format="ixt-sec:durwordsen">two years</ix:nonNumeric></div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage" id="Fact_54f16a3082454b16a1368f8660393627" contextRef="c20201231" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">18</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
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    <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 <ix:nonNumeric name="ions:MaximumContractMaturityPeriodRange2" id="Fact_649df9025a904bcfad6dc6ab6bd4c304" contextRef="c20200101to20201231" format="ixt-sec:durwordsen">two years</ix:nonNumeric> but within <span style="-sec-ix-hidden:Fact_5b50da2d62974df399b2ebfcfccf0c30">three and a half years</span></div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeAndOneHalfYearsPercentage" id="Fact_d60e9c8e586b428c886b9d9653ac0f6e" contextRef="c20201231" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">9</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
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    <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 colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage" id="Fact_298fc5ad20a2442399af2cd8e8215ece" contextRef="c20201231" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">100</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br /></div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">As illustrated above, at December 31, 2020, <ix:nonFraction name="ions:AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage" id="Fact_971b070bcf6846b8970847cdbaef1457" contextRef="c20201231" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">91</ix:nonFraction> percent of our available-for-sale securities had a maturity of less than <ix:nonNumeric name="ions:MaximumContractMaturityPeriodRange2" id="Fact_e4aa3be8fcd040d0bcd0def824af337d" contextRef="c20200101to20201231" format="ixt-sec:durwordsen">two years</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;">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>
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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, 2020, we had an ownership interest of less than 20 percent <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">in </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><ix:nonFraction name="ions:NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment" id="Fact_c487d989afb240aaae9be0536d4b8656" contextRef="c20201231" unitRef="U007" decimals="INF" scale="0" format="ixt-sec:numwordsen">seven</ix:nonFraction></span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> private companies and </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><ix:nonFraction name="ions:NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment" id="Fact_cc8fa179d30548a7b52fcdc75fe7eeee" contextRef="c20201231" unitRef="U007" decimals="INF" scale="0" format="ixt-sec:numwordsen">two</ix:nonFraction></span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> public companies with which we conduct business. The privately-held companies are </span>Aro Biotherapeutics, Atlantic Pharmaceuticals Limited, Dynacure SAS, Empirico, Inc., Flamingo Therapeutics BV, Seventh Sense Biosystems and Suzhou Ribo Life Science Co, Ltd. The publicly traded companies are ATL and ProQR.</div>
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<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">F-<span>24</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 following is a summary of our investments (in thousands):</div>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>
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    <td colspan="2" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#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 (2)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis" id="Fact_f00bcd75b4b842ec98fdc045c48c2576" contextRef="c20201231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_USTreasurySecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">307,576</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax" id="Fact_d6b1880a34fc425f848f593694e21d3b" contextRef="c20201231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_USTreasurySecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">233</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax" id="Fact_52ee12eba4604cd6beb6d916ef074d49" contextRef="c20201231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_USTreasurySecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">9</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#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>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
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  </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 colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis" id="Fact_688e35bb2cf942a2a74c8b48050fabc7" contextRef="c20201231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_OtherDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">5,191</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax" id="Fact_2b0a5f7590f047e8bfcb254acbc3e8c3" contextRef="c20201231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_OtherDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:zerodash">&#8212;</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax" id="Fact_8357f27e3ca9408597cf57745fe674c1" contextRef="c20201231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_OtherDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">7</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_a8e32eee3e094e80bb188937441c5088" contextRef="c20201231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_OtherDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">5,184</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total securities with a maturity of one year or less</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis" id="Fact_06b37f3d76b24645b428aed40ef7519d" contextRef="c20201231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_DebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">1,025,454</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax" id="Fact_868aecd154b3411fad39ee7f067ae085" contextRef="c20201231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_DebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">2,977</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax" id="Fact_27ce74de3a8d48ed86f8ce84429f7f33" contextRef="c20201231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_DebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">71</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_7cbbbf68a23c4d05acea3eb703650eb7" contextRef="c20201231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_DebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">1,028,360</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#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</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis" id="Fact_68c90e44ae7142faa5c935422fe6ca01" contextRef="c20201231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_CorporateDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">325,079</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax" id="Fact_0ecb6c8cead3473f9be6b9fc2b15d79f" contextRef="c20201231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_CorporateDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">4,941</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax" id="Fact_4f2e99491c92483882c5013894e5a3b4" contextRef="c20201231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_CorporateDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">40</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_8078467ba1d947589f274b1470ccc8c7" contextRef="c20201231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_CorporateDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">329,980</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#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 colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis" id="Fact_e4c79d28e0dd438c896e0c5148cdbae0" contextRef="c20201231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">80,099</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax" id="Fact_c3fb53b35b5e4f0a801fb17377bbe452" contextRef="c20201231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">185</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax" id="Fact_f20247b6d2f84ccbbb1dbab68b9cd3d6" contextRef="c20201231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">9</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_a656c02b450b4ae39000dbd1d10a2d67" contextRef="c20201231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">80,275</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#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 colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis" id="Fact_160b2612c5ff403daa0b23ecdd2866db" contextRef="c20201231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_USTreasurySecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">50,318</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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  <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>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax" id="Fact_fee237831c094d6db8d66deaea062f6b" contextRef="c20201231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">91</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#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 colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis" id="Fact_6c8222f000a7424c8a7ed0bf8d85cff3" contextRef="c20201231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_OtherDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">1,041</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax" id="Fact_0062d9c59fee4f9ba9d6eb036a4bdb3d" contextRef="c20201231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_OtherDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:zerodash">&#8212;</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax" id="Fact_44ec9429331b405ea2219868b2cfdb87" contextRef="c20201231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_OtherDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:zerodash">&#8212;</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_f56250cd9b734053925cfd136e9435fa" contextRef="c20201231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_OtherDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">1,041</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total securities with a maturity of more than one year</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis" id="Fact_b71803caad4d4886ad41f6bbc5e209f5" contextRef="c20201231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_DebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">488,316</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax" id="Fact_8a0a49d9cc1e4c129249d0be27e415f2" contextRef="c20201231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_DebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">5,600</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax" id="Fact_0ca92b9c73b2492aadcfbe4f82a50cb4" contextRef="c20201231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_DebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">69</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_91167061047b48f4b8610c1a21447584" contextRef="c20201231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_DebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">493,847</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total available-for-sale securities</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis" id="Fact_a5e37551797746d7832fc5653898ad64" contextRef="c20201231_InvestmentTypeAxis_DebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">1,513,770</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax" id="Fact_5784263002924b25aff1cb14f626bf7f" contextRef="c20201231_InvestmentTypeAxis_DebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">8,577</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax" id="Fact_7654b51ce0a5448fa1c5723b77e4a3cd" contextRef="c20201231_InvestmentTypeAxis_DebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">140</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_fb3ebfc0325446129501360d15bf62ff" contextRef="c20201231_InvestmentTypeAxis_DebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">1,522,207</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#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 colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total equity securities included in deposits and other assets (4)</div></td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:EquitySecuritiesFvNi" id="Fact_acab1218ec2e41199e1b320128741143" contextRef="c20201231_InvestmentTypeAxis_EquitySecuritiesPrivateCompaniesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">31,000</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
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  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total equity securities</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:EquitySecuritiesFvNiCost" id="Fact_1f62fdc7a62342f68a33d50b3bde0a58" contextRef="c20201231_InvestmentTypeAxis_EquitySecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">19,774</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:EquitySecuritiesFvNiUnrealizedGain" id="Fact_c2b1f14b00d941b6b317ee97742c8d96" contextRef="c20200101to20201231_InvestmentTypeAxis_EquitySecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">15,938</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:EquitySecuritiesFvNiUnrealizedLoss" id="Fact_9d1928afc7224324b66d25fddff38253" contextRef="c20200101to20201231_InvestmentTypeAxis_EquitySecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">2,681</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:EquitySecuritiesFvNi" id="Fact_594521b1bd6241bea5eaec95f58271c0" contextRef="c20201231_InvestmentTypeAxis_EquitySecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">33,031</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
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  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 4px; background-color: #FFFFFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total available-for-sale and equity securities</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiCost" id="Fact_afee4ce7ef954363a1010e810f1ae960" contextRef="c20201231" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">1,533,544</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedGain" id="Fact_a346c4f456874316909407a757ecc1b7" contextRef="c20201231" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">24,515</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedLoss" id="Fact_0bd6c064edff43c09905fc28e289473e" contextRef="c20201231" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">2,821</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNi" id="Fact_f35d561e61484f2295cadeeb2d03bdbd" contextRef="c20201231" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">1,555,238</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
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</ix:continuation></ix:continuation><ix:continuation id="Text_e353871cf1c24ed8975d519479a1a5113" continuedAt="Text_e353871cf1c24ed8975d519479a1a5114"><ix:continuation id="Text_b9c7b283940c4cd6a2a40792997c39f615" continuedAt="Text_b9c7b283940c4cd6a2a40792997c39f616">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_e353871cf1c24ed8975d519479a1a5114" continuedAt="Text_e353871cf1c24ed8975d519479a1a5115"><ix:continuation id="Text_b9c7b283940c4cd6a2a40792997c39f616" continuedAt="Text_b9c7b283940c4cd6a2a40792997c39f617">
<table cellpadding="0" cellspacing="0" id="za103de634c4d4cc69d2c374dfbfb01cd" 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" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
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  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Losses</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Fair Value</div></td>
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  </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>
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    <td colspan="2" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#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 (2)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis" id="Fact_8ea119980dc64034994a6b7ad86f848c" contextRef="c20191231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_CorporateDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">669,665</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax" id="Fact_6df2fbe2752e4bd0bb77abf8abe0ae29" contextRef="c20191231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_CorporateDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">1,451</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax" id="Fact_73421ff544c5487b9e733e95b060b569" contextRef="c20191231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_CorporateDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">43</ix:nonFraction></div></td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_c85091a5a55a45a881f09b4c8c70a29c" contextRef="c20191231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_CorporateDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">671,073</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#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 colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis" id="Fact_da1b311c89004135b55ecee7befa549d" contextRef="c20191231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">188,216</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_ba83c8acf52443779871f0f7f21e0f69" contextRef="c20191231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">188,476</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#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 (2)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis" id="Fact_267f46317f0b40caa2f037611c038a1e" contextRef="c20191231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_USTreasurySecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">327,670</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax" id="Fact_2d25c6a792494377addd272a5b8dded6" contextRef="c20191231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_USTreasurySecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">232</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax" id="Fact_f56cc4d0d90d4e7fbb8f72585969858c" contextRef="c20191231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_USTreasurySecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">27</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_0c7a5d61dae34de8a30b14b8802b8785" contextRef="c20191231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_USTreasurySecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">327,875</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#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 colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis" id="Fact_2665cd241db44217ad8643b9ae2a63da" contextRef="c20191231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">21,065</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax" id="Fact_5244a18f7849464e8277366dd5790037" contextRef="c20191231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">26</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax" id="Fact_703babc31466440681b56330914ed672" contextRef="c20191231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">5</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_8732df0d6eac436fa8da11aab067289a" contextRef="c20191231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">21,086</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total securities with a maturity of one year or less</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis" id="Fact_f91f4bf7895e4255b6fb1606547e04c4" contextRef="c20191231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_DebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">1,206,616</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax" id="Fact_58f014330e0d46f68ac56681d9bcc775" contextRef="c20191231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_DebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">2,012</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax" id="Fact_4d687e924d2549c292e3b98c471a8b1c" contextRef="c20191231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_DebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">118</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_5b653caa5875494f883c075c43b1bf5c" contextRef="c20191231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_DebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">1,208,510</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#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 colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis" id="Fact_90b66da8071a4a14ae79ae20e35a4725" contextRef="c20191231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_CorporateDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">428,627</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
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  </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 colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_01ade62c43ae4d1d9d121b813ab06110" contextRef="c20191231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">140,928</ix:nonFraction></div></td>
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  </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 colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis" id="Fact_1a4e37f7b16f498caa99b193ac3977d1" contextRef="c20191231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_USTreasurySecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">35,822</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax" id="Fact_9e774f36b3824b5da1f596ef542f70e8" contextRef="c20191231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_USTreasurySecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">9</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax" id="Fact_fcf3826f90e44039b289f8286697222d" contextRef="c20191231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_USTreasurySecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">12</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_3834f60c806146fdb57604df4ca44d5f" contextRef="c20191231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_USTreasurySecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">35,819</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#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 colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis" id="Fact_3b50fc36268c472c83543a498f74c6a3" contextRef="c20191231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">19,309</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax" id="Fact_3cc6fe9c6c684eabbb359b5b57a83381" contextRef="c20191231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">18</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax" id="Fact_f9f79be238454b459039ee2cf29f6635" contextRef="c20191231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">6</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_285a93f311de42a8b8b01192c7d0cee6" contextRef="c20191231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">19,321</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total securities with a maturity of more than one year</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis" id="Fact_be05404e83c643348777fa91b0e1b9ba" contextRef="c20191231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_DebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">624,746</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax" id="Fact_80c5acbabb8c4f0bb30f07636779a6ef" contextRef="c20191231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_DebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">2,995</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax" id="Fact_2d2b1cb797c643148d37d334e933eeb2" contextRef="c20191231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_DebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">178</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_2bbc29a667a94cb99ff6c9f040ebeea6" contextRef="c20191231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_DebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">627,563</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total available-for-sale securities</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis" id="Fact_8caafd476a3541b9aef7c098cc041e94" contextRef="c20191231_InvestmentTypeAxis_DebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">1,831,362</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax" id="Fact_609132a66d2f4130b140a88c2fb0c89d" contextRef="c20191231_InvestmentTypeAxis_DebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">5,007</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_4de7d9b3be6d447db4b3c3fe0b8f036b" contextRef="c20191231_InvestmentTypeAxis_DebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">1,836,073</ix:nonFraction></div></td>
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  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Equity securities:</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
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  <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;">Total equity securities included in other current assets (3)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:EquitySecuritiesFvNiCost" id="Fact_ddb646a5d0f1447b92caf9f07a627fcd" contextRef="c20191231_InvestmentTypeAxis_EquitySecuritiesPubliclyTradedCompaniesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">4,712</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:EquitySecuritiesFvNiUnrealizedGain" id="Fact_88ed4a2745c54e14a622755a003ef7d5" contextRef="c20190101to20191231_InvestmentTypeAxis_EquitySecuritiesPubliclyTradedCompaniesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:zerodash">&#8212;</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:EquitySecuritiesFvNiUnrealizedLoss" id="Fact_b4cdd38512ef47d9b5d3df0de25143e1" contextRef="c20190101to20191231_InvestmentTypeAxis_EquitySecuritiesPubliclyTradedCompaniesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">870</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:EquitySecuritiesFvNi" id="Fact_c71d4b805e374b9696b1907d0c3b8708" contextRef="c20191231_InvestmentTypeAxis_EquitySecuritiesPubliclyTradedCompaniesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">3,842</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total equity securities included in deposits and other assets (4)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:EquitySecuritiesFvNiCost" id="Fact_fd07a2a1606f48d78bc5fb285d90a137" contextRef="c20191231_InvestmentTypeAxis_EquitySecuritiesPrivateCompaniesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">10,000</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:EquitySecuritiesFvNiUnrealizedGain" id="Fact_f166a5e138d3457b82d04bfee0b2aaa8" contextRef="c20190101to20191231_InvestmentTypeAxis_EquitySecuritiesPrivateCompaniesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:zerodash">&#8212;</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:EquitySecuritiesFvNiUnrealizedLoss" id="Fact_377148fd543d4bcd9b069e1883f63342" contextRef="c20190101to20191231_InvestmentTypeAxis_EquitySecuritiesPrivateCompaniesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:zerodash">&#8212;</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:EquitySecuritiesFvNi" id="Fact_250e88ec455a48818d6c542e743f1801" contextRef="c20191231_InvestmentTypeAxis_EquitySecuritiesPrivateCompaniesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">10,000</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total equity securities</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:EquitySecuritiesFvNiCost" id="Fact_8cbb173fbf424d2cae5761cfe86aa386" contextRef="c20191231_InvestmentTypeAxis_EquitySecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">14,712</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:EquitySecuritiesFvNiUnrealizedGain" id="Fact_c7bf32577ac44c999892ccbf176d194e" contextRef="c20190101to20191231_InvestmentTypeAxis_EquitySecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:zerodash">&#8212;</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:EquitySecuritiesFvNiUnrealizedLoss" id="Fact_7050ac2adf394b31b986c11c8b0618f6" contextRef="c20190101to20191231_InvestmentTypeAxis_EquitySecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">870</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:EquitySecuritiesFvNi" id="Fact_b3f9adef6e924b3c91c0bc0573208fed" contextRef="c20191231_InvestmentTypeAxis_EquitySecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">13,842</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 4px; background-color: #FFFFFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total available-for-sale and equity securities</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiCost" id="Fact_c31aca2dbed748588049458efeea09a7" contextRef="c20191231" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">1,846,074</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedGain" id="Fact_c255d1502e344319b6e94f49f85ceeb8" contextRef="c20191231" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">5,007</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedLoss" id="Fact_442681fd5f144b86afca5af925fffb02" contextRef="c20191231" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">1,166</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNi" id="Fact_59bf550c30564d83b459e349c7ec3c12" contextRef="c20191231" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">1,849,915</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
</table>
</ix:continuation></ix:continuation><ix:continuation id="Text_e353871cf1c24ed8975d519479a1a5115" continuedAt="Text_e353871cf1c24ed8975d519479a1a5116"><ix:continuation id="Text_b9c7b283940c4cd6a2a40792997c39f617" continuedAt="Text_b9c7b283940c4cd6a2a40792997c39f618">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">________________</div>
</ix:continuation></ix:continuation><ix:continuation id="Text_e353871cf1c24ed8975d519479a1a5116" continuedAt="Text_e353871cf1c24ed8975d519479a1a5117"><ix:continuation id="Text_b9c7b283940c4cd6a2a40792997c39f618" continuedAt="Text_b9c7b283940c4cd6a2a40792997c39f619">
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  <tr>
    <td style="width: 36pt; vertical-align: top; align: right; 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_41dc381daf5c41bb92e06d06481bf7a5" footnoteRole="http://www.xbrl.org/2003/role/footnote" xml:lang="en-US">We hold our available-for-sale securities at amortized cost.</ix:footnote></div></td>
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    <td style="width: 36pt; vertical-align: top; align: right; 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_88fe67a8cca841eaa8660167eec626fe" footnoteRole="http://www.xbrl.org/2003/role/footnote" xml:lang="en-US">Includes investments classified as cash equivalents on our consolidated balance sheet.</ix:footnote></div></td>
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</ix:continuation></ix:continuation><ix:continuation id="Text_e353871cf1c24ed8975d519479a1a51110" continuedAt="Text_e353871cf1c24ed8975d519479a1a51111"><ix:continuation id="Text_b9c7b283940c4cd6a2a40792997c39f622" continuedAt="Text_b9c7b283940c4cd6a2a40792997c39f623">
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    <td style="width: 36pt; vertical-align: top; align: right; 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_33f87045331d4d29a03153170558d0a1" footnoteRole="http://www.xbrl.org/2003/role/footnote" xml:lang="en-US">Our equity securities included in other current assets consisted of our investments in publicly traded companies. We recognize publicly traded equity securities at fair value.</ix:footnote></div></td>
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    <td style="width: 36pt; vertical-align: top; align: right; 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;"><ix:footnote id="Foot_92f3ab0ee45a44b9baf44a6e4c6792b4" footnoteRole="http://www.xbrl.org/2003/role/footnote" xml:lang="en-US" continuedAt="Foot_4e0febe4c84f422f9af27b26e14d70161">Our equity securities included in deposits and other assets consisted of our investments in privately held companies. We recognize our private company equity securities at</ix:footnote></span><ix:continuation id="Foot_4e0febe4c84f422f9af27b26e14d70161" continuedAt="Foot_4e0febe4c84f422f9af27b26e14d70162"> 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</ix:continuation><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><ix:continuation id="Foot_4e0febe4c84f422f9af27b26e14d70162"> on our consolidated balance sheet.</ix:continuation></span></div></td>
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<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">F-<span>25</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;">The </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">following is a summary of our investments we considered to be temporarily impaired at</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#xA0;</span>December 31, 2020<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#xA0;</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(in thousands). All of these investments have less than 12 months of temporary impairment. </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We believe that the decline in value of these securities is temporary and is primarily related to the change in market interest rates since purchase. We believe it is more likely than not that we will be able to hold our debt securities to maturity. Therefore, we anticipate full recovery of our debt securities&#8217; amortized cost basis at maturity.</span></div>
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  <tr>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Other municipal debt securities</div></td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss" id="Fact_251f3241197c4358963f5bbb05ed251a" contextRef="c20201231_InvestmentTypeAxis_OtherDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">7</ix:nonFraction></div></td>
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  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThanTwelveMonthsFairValue" id="Fact_79754104b6c64388ae4f4c5345eb981e" contextRef="c20201231" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">284,148</ix:nonFraction></div></td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>
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  </tr>
</table>
</ix:continuation></ix:continuation></div>
<div style="text-align: left;"><br /></div>
<div><ix:nonNumeric name="us-gaap:DebtAndCapitalLeasesDisclosuresTextBlock" id="Text_1f7799e29d9c4fd5ac2c30d64ad9a625" contextRef="c20200101to20201231" escape="true" continuedAt="Text_4833ac4fc9564ba5934d82d9e5f77e431">
<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">3. Long-Term Obligations and Commitments</div>
</ix:nonNumeric><ix:continuation id="Text_4833ac4fc9564ba5934d82d9e5f77e431" continuedAt="Text_4833ac4fc9564ba5934d82d9e5f77e432">
<div><br /></div>
</ix:continuation><ix:nonNumeric name="us-gaap:ScheduleOfDebtInstrumentsTextBlock" id="Text_487975f5bd5542cbb02179bbd1a60f54" contextRef="c20200101to20201231" escape="true" continuedAt="Text_24f6cb308d7444f8ad815eb2468e19c01"><ix:continuation id="Text_4833ac4fc9564ba5934d82d9e5f77e432" continuedAt="Text_4833ac4fc9564ba5934d82d9e5f77e433">
<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:continuation></ix:nonNumeric><ix:continuation id="Text_24f6cb308d7444f8ad815eb2468e19c01" continuedAt="Text_24f6cb308d7444f8ad815eb2468e19c02"><ix:continuation id="Text_4833ac4fc9564ba5934d82d9e5f77e433" continuedAt="Text_4833ac4fc9564ba5934d82d9e5f77e434">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_24f6cb308d7444f8ad815eb2468e19c02" continuedAt="Text_24f6cb308d7444f8ad815eb2468e19c03"><ix:continuation id="Text_4833ac4fc9564ba5934d82d9e5f77e434" continuedAt="Text_4833ac4fc9564ba5934d82d9e5f77e435">
<table cellpadding="0" cellspacing="0" id="z491d0b86fdec4ab1bf93c193d82169f5" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"></div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="6" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><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" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2020</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2019</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ConvertibleDebt" id="Fact_cc24fb43c0744f1c98325749d3d1c0eb" contextRef="c20201231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">455,719</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ConvertibleDebt" id="Fact_65be5fa6a2434040beb0d9ae2a2ca4aa" contextRef="c20191231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">434,711</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
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  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ConvertibleDebt" id="Fact_cab8c72e622844b2bff548c7151f9645" contextRef="c20201231_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">293,161</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ConvertibleDebt" id="Fact_263762c2879f49e19df48df907a46cf1" contextRef="c20191231_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">275,333</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Long-term mortgage debt</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:LoansPayableToBank" id="Fact_7526ddee5b884532b24be01e4d495612" contextRef="c20201231" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">59,984</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:LoansPayableToBank" id="Fact_1a31cb06bce14608b6b4bc53c537a2e8" contextRef="c20191231" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">59,913</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#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;">Leases and other obligations</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:LeasesAndOtherObligations" id="Fact_4f4ce1cf534445a182bc4dc79c4da3ed" contextRef="c20201231" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">30,710</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:LeasesAndOtherObligations" id="Fact_14ee837947184542bf24c811e63d710b" contextRef="c20191231" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">17,569</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtAndCapitalLeaseObligations" id="Fact_67f1e8de33db4b3ba71a251d6969a0e4" contextRef="c20201231" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">839,574</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtAndCapitalLeaseObligations" id="Fact_0db6c0acf39c4704b8b7fb0682124be0" contextRef="c20191231" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">787,526</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#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;">Less: current portion (1)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:LongTermDebtAndCapitalLeaseObligationsCurrent" id="Fact_66f728e151b74fe99d367269b42506b7" contextRef="c20201231" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">300,462</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:LongTermDebtAndCapitalLeaseObligationsCurrent" id="Fact_6b303576d07b435ebdc0b94cf229a5a7" contextRef="c20191231" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">2,026</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:LongTermDebtAndCapitalLeaseObligations" id="Fact_85488b1118b143d68b8dce7fa49d282e" contextRef="c20191231" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">785,500</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</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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<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="za3bbe36629904c01b690cbe109c76d9b">
  <tr>
    <td style="width: 36pt; vertical-align: top; align: right; 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_9a970986ba874d05b3ae45569fb070a7" footnoteRole="http://www.xbrl.org/2003/role/footnote" xml:lang="en-US" continuedAt="Foot_5debec2967b94797baa5bbf2ae4fff7a1">We classified the carrying value of our <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_86c5cefc4d6e48cd81189a7e61f827c7" contextRef="c20201231_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">1</ix:nonFraction></ix:footnote><ix:continuation id="Foot_5debec2967b94797baa5bbf2ae4fff7a1">% Notes as a current liability on our consolidated balance sheet at December 31, 2020 because it matures in November 2021.</ix:continuation></div></td>
  </tr>
</table>
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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;">Convertible Notes and Call Spread</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;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_4bea2f4a817c43a9a04ad1e23ed64460" contextRef="c20201231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:numdotdecimal">0.125</ix:nonFraction> Percent</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#xA0;</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Convertible Senior Notes</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 December 2019, we entered into privately negotiated exchange and/or subscription agreements with certain new investors and certain holders of our existing <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_1870776015794dfc8ef5f8b1e447336c" contextRef="c20201231_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">1</ix:nonFraction>%</span> Notes to exchange $<ix:nonFraction name="us-gaap:DebtInstrumentRepurchasedFaceAmount" id="Fact_c20e03a6b29c48f297e64a4679fa9c5f" contextRef="c20191231_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember" unitRef="U001" decimals="-5" scale="6" format="ixt:numdotdecimal">375.6</ix:nonFraction> million of our <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_b16e24609ee743c7bc4f5ff336547c52" contextRef="c20201231_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">1</ix:nonFraction>%</span> Notes for $<ix:nonFraction name="us-gaap:DebtInstrumentFaceAmount" id="Fact_712a7e9c20e2446687234da15c55574b" contextRef="c20191231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentIssuedInExchangeFor1PercentNotesMember" unitRef="U001" decimals="-5" scale="6" format="ixt:numdotdecimal">439.3</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#xA0;</span>million of our <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_ee88310c4297461c9e36d233141d8e6d" contextRef="c20201231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:numdotdecimal">0.125</ix:nonFraction>% Notes, and to issue $<ix:nonFraction name="us-gaap:DebtInstrumentFaceAmount" id="Fact_4fb2d114d9054ec1ab34d5bc942df800" contextRef="c20191231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentIssuedUnderSubscriptionAgreementsMember" unitRef="U001" decimals="-5" scale="6" format="ixt:numdotdecimal">109.5</ix:nonFraction> million of our <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_91e74186c76c4d6f9f3b0792c25a8126" contextRef="c20201231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:numdotdecimal">0.125</ix:nonFraction>% Notes. We completed this exchange to reduce our cash interest payments, increase our conversion price and extend our maturity for a large portion of our debt. Additionally, i<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">n conjunction with the December 2019 exchange, 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_b678b3b287184ce883f541de9b3318b0" contextRef="c20201231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:numdotdecimal">0.125</ix:nonFraction>% Notes<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> by increasing the effective conversion price even further.</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;">Interest is payable semi-annually on June 15 and December 15 of each year for the <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_243b14e84d1842d5a1561cbadfdc7501" contextRef="c20201231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:numdotdecimal">0.125</ix:nonFraction>%</span> Notes. The <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_aca37e6592634dfea9eef91832500545" contextRef="c20201231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:numdotdecimal">0.125</ix:nonFraction>%</span> Notes are convertible at the option of the note holders prior to August 1, 2024 only under certain conditions. On or after August 1, 2024, the <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_93e447d776f44e03b6def90e87589945" contextRef="c20201231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:numdotdecimal">0.125</ix:nonFraction>%</span> Notes are initially convertible into approximately <ix:nonFraction name="us-gaap:DebtInstrumentConvertibleNumberOfEquityInstruments" id="Fact_bdb0f6e71c464c07a7fcbc83441b7a3d" contextRef="c20200101to20201231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">6.6</ix:nonFraction> million shares of common stock at a conversion price of approximately $<ix:nonFraction name="us-gaap:DebtInstrumentConvertibleConversionPrice1" id="Fact_11e47b80c0ea4c0b84c2b33098b7b371" contextRef="c20201231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U004" decimals="2" scale="0" format="ixt:numdotdecimal">83.28</ix:nonFraction> per share. We will 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 <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_1853ce4f8b7b48fd95ac8e504bc98be7" contextRef="c20201231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:numdotdecimal">0.125</ix:nonFraction>%</span> Notes prior to maturity, and no sinking fund is provided for them. If we undergo a fundamental change, holders may require us to purchase for cash all or any portion of their <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_dfcecee6bd19487eaf70edea7c8f81ca" contextRef="c20201231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:numdotdecimal">0.125</ix:nonFraction>%</span> Notes at a purchase price equal to <ix:nonFraction name="ions:DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange" id="Fact_c714ec93e83942c5ab6d1b22a0ca3d32" contextRef="c20200101to20201231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">100</ix:nonFraction> percent of the principal amount of the notes to be purchased, plus accrued and unpaid interest to, but excluding, the fundamental change purchase date.</div>
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<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">F-<span>26</span></div>
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</ix:continuation><ix:nonNumeric name="us-gaap:ConvertibleDebtTableTextBlock" id="Text_599676c995b8459d807f45a7ee7d2f44" contextRef="c20200101to20201231" escape="true" continuedAt="Text_8fc9cff15648424dbd3d980886e600c31"><ix:continuation id="Text_4833ac4fc9564ba5934d82d9e5f77e4316" continuedAt="Text_4833ac4fc9564ba5934d82d9e5f77e4317">
<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, 2020, we had the following <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_0e5fc93e472946cc9732114aaf09fe86" contextRef="c20201231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:numdotdecimal">0.125</ix:nonFraction>%</span> Notes outstanding (amounts in millions except price per share data):</div>
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<div><br /></div>
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<table cellpadding="0" cellspacing="0" id="zd6b190b45e7940aebc9709e23b39ca57" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
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  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtInstrumentCarryingAmount" id="Fact_57777fe91a8e4f29a6ef267206ee9a82" contextRef="c20201231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U001" decimals="-5" scale="6" format="ixt:numdotdecimal">548.8</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
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  <tr>
    <td valign="bottom" style="vertical-align: top; white-space: nowrap;"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Maturity date</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; white-space: nowrap;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: top;"><div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonNumeric name="us-gaap:DebtInstrumentMaturityDate" id="Fact_717eebd3862f421ca0587a6d283178c9" contextRef="c20200101to20201231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" format="ixt:datemonthdayyearen">December 15, 2024</ix:nonNumeric></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: top; width: 88%; background-color: #CCEEFF; white-space: nowrap;"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Interest rate</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_f57c2bf3954e4b06bdb6e73d241258c0" contextRef="c20201231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:numdotdecimal">0.125</ix:nonFraction></div></td>
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  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: top; width: 88%; white-space: nowrap;"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Conversion price per share</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: top; width: 88%; background-color: #CCEEFF; white-space: nowrap;"><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" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtInstrumentConvertibleNumberOfEquityInstruments" id="Fact_a8446d3306204ee4841e3d9e1f0b0e88" contextRef="c20200101to20201231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">6.6</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#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;">The following table summarizes information about the equity and liability components of our outstanding </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_6b7a3e820d8b4273b11b894d2ba67007" contextRef="c20201231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:numdotdecimal">0.125</ix:nonFraction>%</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> Notes (in millions). We measured the fair values of the convertible notes outstanding based on quoted market prices, which is a Level 2 measurement at December 31, </span>2020<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> and </span>2019<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">:</span></div>
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  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Carrying value of equity component</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#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-style: italic;">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;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Additionally, i</span>n conjunction with the December 2019 exchange, 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 style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_1eb86644c97d419d93743b0512053bf1" contextRef="c20201231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:numdotdecimal">0.125</ix:nonFraction>%</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> Notes</span> by increasing the conversion price even further. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">The call spread cost us $</span><ix:nonFraction name="ions:CallSpread" id="Fact_e9d4aad460e644458ec285d77482089c" contextRef="c20191201to20191231" unitRef="U001" decimals="-5" scale="6" format="ixt:numdotdecimal">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_0994e1dc04004d2382a34c5e13628fa1" contextRef="c20191201to20191231" unitRef="U001" decimals="-5" scale="6" format="ixt:numdotdecimal">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_129b374a00b44cc89defdbe6353d570e" contextRef="c20191201to20191231" unitRef="U001" decimals="-5" scale="6" format="ixt:numdotdecimal">56.1</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million we received for selling the warrants. We increased our effective conversion price to $</span><ix:nonFraction name="ions:DebtInstrumentConvertibleConversionPriceIncludingCallSpread" id="Fact_47a59f154aa241e092e3cb2ff63ce803" contextRef="c20191231" unitRef="U004" decimals="2" scale="0" format="ixt:numdotdecimal">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><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_d2c7414fb1da467f803bda3bed07ee1b" contextRef="c20201231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:numdotdecimal">0.125</ix:nonFraction>%</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> Notes</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. </span>We accounted for our call spread transactions using the Derivatives and Hedging &#8211; Contracts in Entity&#8217;s Own Equity accounting guidance contained in Topic 815. We determined that the call spread transactions meet the definition of a derivative, are indexed to our stock and meet the criteria to be classified in shareholders&#8217; equity.</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;">Similar to our </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_7b8ba4a02a954d6599d6024b18243e28" contextRef="c20201231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:numdotdecimal">0.125</ix:nonFraction>%</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> Notes</span><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><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_7a8ce4e67bd54f9a987fa4ed687d2240" contextRef="c20201231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:numdotdecimal">0.125</ix:nonFraction>%</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> Notes</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. The note hedges will expire upon maturity of </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_3d6dde904f90445d93305af76cf6eda2" contextRef="c20201231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:numdotdecimal">0.125</ix:nonFraction>%</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> Notes</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, or December 2024. The note hedges and warrants are separate transactions and are not part of the terms of our </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_9bb8ca84262b41cdb2763e3d9fb4239f" contextRef="c20201231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:numdotdecimal">0.125</ix:nonFraction>%</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> Notes</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. The holders of the </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_4451c7a7d9d84d2780c91b575f56d194" contextRef="c20201231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:numdotdecimal">0.125</ix:nonFraction>%</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> Notes</span><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;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We recorded the aggregate amount paid for the note hedges and the aggregate amount received for the warrants in additional paid-in capital in our consolidated balance sheet. </span>We reassess our ability to continue to classify the note hedges and warrants in shareholders&#8217; equity at each reporting period. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We excluded shares under the note hedges from our calculation of diluted earnings per share as they were antidilutive. We will include the shares issuable under the 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.</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;"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_a138942c9a354318adbd51f712f26e3a" contextRef="c20201231_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">1</ix:nonFraction> Percent Convertible Senior Notes</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In November 2014, we completed a $<ix:nonFraction name="us-gaap:DebtInstrumentFaceAmount" id="Fact_ae69fb3096d04ec386cf18bda382f2ac" contextRef="c20141130_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">500</ix:nonFraction> million offering of convertible senior notes, which mature in 2021 and bear interest at <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_5aa11ec0f17e45ff8bae60179009c497" contextRef="c20201231_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">1</ix:nonFraction> percent. We used a substantial portion of the net proceeds from the issuance of the <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_eb07200e0d7e47e8980856189249c81b" contextRef="c20201231_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">1</ix:nonFraction>% Notes to repurchase $<ix:nonFraction name="us-gaap:DebtInstrumentRepurchasedFaceAmount" id="Fact_a7cfea2321f84b2196ac4f1c44ae3c68" contextRef="c20141130_DebtInstrumentAxis_ConvertibleSeniorNotes275PercentMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">140</ix:nonFraction> million in principal of our <span style="-sec-ix-hidden:Fact_5720e35e625f4851a419d661f07222c0">2&#190; percent</span> convertible senior notes, or <span style="-sec-ix-hidden:Fact_aab0fa84211849a9a9227eb0f2f81996">2&#190;%</span>% Notes. In December 2016, we issued an additional $<ix:nonFraction name="us-gaap:DebtInstrumentFaceAmount" id="Fact_40b369e59fd54938a3c76d88c97539ee" contextRef="c20161231_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember" unitRef="U001" decimals="-5" scale="6" format="ixt:numdotdecimal">185.5</ix:nonFraction> million of <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_8ed18eaff8004156b3c13189a20eab93" contextRef="c20201231_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">1</ix:nonFraction>% Notes in exchange for the redemption of $<ix:nonFraction name="us-gaap:DebtInstrumentRepurchasedFaceAmount" id="Fact_c377503f2bbe44b488a9c42e68e820e1" contextRef="c20161231_DebtInstrumentAxis_ConvertibleSeniorNotes275PercentMember" unitRef="U001" decimals="-5" scale="6" format="ixt:numdotdecimal">61.1</ix:nonFraction> million of our <span style="-sec-ix-hidden:Fact_1a854ab02ffa46d48ab09b0a92e8e673">2&#190;%</span>% Notes. In December 2019, we exchanged a portion of our <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_72efeb8706804393b794e69da1859ca9" contextRef="c20201231_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">1</ix:nonFraction>% Notes for <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_52a80f2cfee04eb587e3582cda96ceb8" contextRef="c20201231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:numdotdecimal">0.125</ix:nonFraction>%</span> Notes. As a result, the principal balance of <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_7f4517d888a848e8aa549382b1f663fa" contextRef="c20201231_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">1</ix:nonFraction>% Notes was $<ix:nonFraction name="us-gaap:DebtInstrumentCarryingAmount" id="Fact_73cc83fd51084b739e29305c9bcf6432" contextRef="c20201231_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember" unitRef="U001" decimals="-5" scale="6" format="ixt:numdotdecimal">309.9</ix:nonFraction> million. Additionally, we recorded a $<ix:nonFraction name="us-gaap:GainsLossesOnExtinguishmentOfDebt" id="Fact_e56c4f7d46164e5682b05b11e5a76ff0" contextRef="c20191201to20191231_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember" unitRef="U001" decimals="-5" scale="6" sign="-" format="ixt:numdotdecimal">21.9</ix:nonFraction> million non-cash loss on early retirement of debt, reflecting the early retirement of a significant portion of our <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_21ae763200804eda89d695f565a9b421" contextRef="c20201231_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">1</ix:nonFraction>% Notes in December 2019.</div>
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<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">F-<span>27</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 December 31, 2020, we had the following <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_351f7a4cc22d4c609a76582f7cafaced" contextRef="c20201231_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">1</ix:nonFraction>% Notes outstanding (amounts in millions except price per share data):</div>
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<table cellpadding="0" cellspacing="0" id="z7c00b82b222848c08f211e04a12df732" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
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    <td valign="bottom" style="vertical-align: top; width: 88%; background-color: #CCEEFF; white-space: nowrap;"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Outstanding principal balance</div></td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
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    <td valign="bottom" style="vertical-align: top; white-space: nowrap;"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Maturity date</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; white-space: nowrap;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>
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    <td valign="bottom" style="vertical-align: top; background-color: #CCEEFF; white-space: nowrap;"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Interest rate</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: top; background-color: #CCEEFF;"><div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_3e00958972ef4dd78ced0398e546c3e7" contextRef="c20201231_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">1</ix:nonFraction> percent</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
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    <td valign="bottom" style="vertical-align: top; width: 88%; white-space: nowrap;"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Conversion price per share</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtInstrumentConvertibleConversionPrice1" id="Fact_95d9dc164aba4bc4906d223af6cce4cd" contextRef="c20201231_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember" unitRef="U004" decimals="2" scale="0" format="ixt:numdotdecimal">66.81</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
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    <td valign="bottom" style="vertical-align: top; width: 88%; background-color: #CCEEFF; white-space: nowrap;"><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" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtInstrumentConvertibleNumberOfEquityInstruments" id="Fact_c84bb6217a084a41ad136652cc09e03d" contextRef="c20200101to20201231_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">4.6</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Interest is payable semi-annually in arrears on May 15 and November 15 of each year for the <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_f0bd4c0c0e7f4e15a243cf31a30d5fe3" contextRef="c20201231_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">1</ix:nonFraction>% Notes. The <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_5195a53072b24193b8693cceb851285c" contextRef="c20201231_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">1</ix:nonFraction>% Notes are convertible at the option of the note holders prior to July 1, 2021 only under certain conditions. On or after July 1, 2021, the <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_599a6c650ba949af823e3721d1dcc7ab" contextRef="c20201231_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">1</ix:nonFraction>% Notes are initially convertible into approximately <ix:nonFraction name="us-gaap:DebtInstrumentConvertibleNumberOfEquityInstruments" id="Fact_c3b8a56b35774f09a683069e7da23a49" contextRef="c20200101to20201231_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">4.6</ix:nonFraction> million shares of common stock at a conversion price of approximately $<ix:nonFraction name="us-gaap:DebtInstrumentConvertibleConversionPrice1" id="Fact_1e3f531b50ce45a78f352059a2aabe03" contextRef="c20201231_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember" unitRef="U004" decimals="2" scale="0" format="ixt:numdotdecimal">66.81</ix:nonFraction> per share. We will 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 <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_fef53aa8a8f64806813c1c9401c10e7c" contextRef="c20201231_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">1</ix:nonFraction>% Notes prior to maturity, and no sinking fund is provided for them. If we undergo a fundamental change, holders may require us to purchase for cash all or any portion of their <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_8147e405f341494fba590f9fd7e1adbe" contextRef="c20201231_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">1</ix:nonFraction>% Notes at a purchase price equal to <ix:nonFraction name="ions:DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange" id="Fact_fdfc68a3935a465f936cbb5325d0f693" contextRef="c20200101to20201231_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">100</ix:nonFraction> percent of the principal amount of the notes to be purchased, plus accrued and unpaid interest to, but excluding, the fundamental change purchase date.</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;">The following table summarizes information about the equity and liability components of our outstanding </span><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_6957f3faaf5447e0a8c23e16d21eb4cd" contextRef="c20201231_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">1</ix:nonFraction>%<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> Notes (in millions). We measured the fair values of the convertible notes outstanding based on quoted market prices, which is a Level 2 measurement at December 31, </span>2020<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> and </span>2019<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">:</span></div>
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<table cellpadding="0" cellspacing="0" id="z6aaac47fd8de480782bc6ae69dceb20c" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
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    <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;"></div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="6" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><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" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
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  <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;">Carrying value of equity component</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtInstrumentConvertibleCarryingAmountOfTheEquityComponent" id="Fact_615b424156904461b65ab8fba56baf57" contextRef="c20201231_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember" unitRef="U001" decimals="-5" scale="6" format="ixt:numdotdecimal">33.5</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><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;">We account for our convertible notes using an accounting standard that requires us to assign a value to our convertible debt equal to the estimated fair value of similar debt instruments without the conversion feature and to record the remaining portion in equity. As a result, we recorded our convertible notes at a discount, which we are amortizing as additional non-cash interest expense over the expected life of the respective debt. We determined our nonconvertible debt borrowing rate using a combination of the present value of the debt&#8217;s cash flows and a Black-Scholes valuation model. The following table summarizes the nonconvertible borrowing rate, effective interest rate and amortization period of our debt discount for our convertible notes:</div>
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<table cellpadding="0" cellspacing="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" id="z2fe2c231c3944d6a8692011908bb0bdd">
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    <td style="width: 2.25%; vertical-align: bottom;">&#160;</td>
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    <td style="width: 1.39%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 28%; vertical-align: bottom; background-color: #CCEEFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtInstrumentMeasurementInput" id="Fact_596bdc839a504047b97a479e25a26ff8" contextRef="c20201231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember_MeasurementInputTypeAxis_MeasurementInputDiscountRateMember" unitRef="U003" decimals="3" scale="-2" format="ixt:numdotdecimal">4.4</ix:nonFraction> percent</div></td>
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    <td style="width: 1.39%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
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  <tr>
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    <td style="width: 2.25%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 28.82%; 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:DebtInstrumentConvertibleRemainingDiscountAmortizationPeriod1" id="Fact_5e9b605d305346328ae877fed8602d67" contextRef="c20200101to20201231_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember" format="ixt-sec:durwordsen">7 years</ix:nonNumeric></div></td>
    <td style="width: 1.39%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">________________</div>
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<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="zfe3e4e94d24b42be98cc86e80ead96fa">
  <tr>
    <td style="width: 36pt; vertical-align: top; align: right; 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_94c9e35c930540ad8f4b6bdd98cbf740" footnoteRole="http://www.xbrl.org/2003/role/footnote" xml:lang="en-US" continuedAt="Foot_cee2484b3700440aa88d4e1bc4a7eed91">For our <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_e30378472c6741629087ed2375181d83" contextRef="c20201231_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">1</ix:nonFraction></ix:footnote><ix:continuation id="Foot_cee2484b3700440aa88d4e1bc4a7eed91">% Notes, our effective interest rate represents our effective interest rate after our December 2019 debt exchange.</ix:continuation></div></td>
  </tr>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our total interest expense for our outstanding senior convertible notes for the years ended December 31, 2020, 2019 and 2018 included $<ix:nonFraction name="us-gaap:AmortizationOfFinancingCostsAndDiscounts" id="Fact_9c53099ee180469b94aa9696977d2880" contextRef="c20200101to20201231" unitRef="U001" decimals="-5" scale="6" format="ixt:numdotdecimal">38.7</ix:nonFraction> million, $<ix:nonFraction name="us-gaap:AmortizationOfFinancingCostsAndDiscounts" id="Fact_bdbef3ccc85649118ae89b354a641e27" contextRef="c20190101to20191231" unitRef="U001" decimals="-5" scale="6" format="ixt:numdotdecimal">39.3</ix:nonFraction> million and $<ix:nonFraction name="us-gaap:AmortizationOfFinancingCostsAndDiscounts" id="Fact_08ed41e893e1431f80a65f44ee96fab5" contextRef="c20180101to20181231" unitRef="U001" decimals="-5" scale="6" format="ixt:numdotdecimal">35.2</ix:nonFraction> million, respectively, of non-cash interest expense related to the amortization of the debt discount and 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; font-weight: bold;">Line of Credit Arrangement</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In June 2015, we entered into a <ix:nonNumeric name="us-gaap:DebtInstrumentTerm" id="Fact_a08d8b007c144c47ba522cd66c16754b" contextRef="c20200101to20201231_CreditFacilityAxis_RevolvingCreditFacilityMember_LineOfCreditFacilityAxis_MorganStanleyPrivateBankNationalAssociationMember" format="ixt-sec:durwordsen">five-year</ix:nonNumeric> revolving line of credit agreement with Morgan Stanley Private Bank, National Association, or Morgan Stanley, which we amended in February 2016. Under the amended credit agreement, Morgan Stanley provided a maximum of $<ix:nonFraction name="us-gaap:LineOfCreditFacilityMaximumBorrowingCapacity" id="Fact_89fd661deb0b4c3fa02f86026008098b" contextRef="c20201231_CreditFacilityAxis_RevolvingCreditFacilityMember_LineOfCreditFacilityAxis_MorganStanleyPrivateBankNationalAssociationMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">30</ix:nonFraction> million of revolving credit for general working capital purposes. During the third quarter of 2019, we paid off our total outstanding borrowings of $<ix:nonFraction name="us-gaap:RepaymentsOfLongTermLinesOfCredit" id="Fact_df1b80118efc4ee18a12e9720dbc121d" contextRef="c20190701to20190930_DebtInstrumentAxis_FixedRateNoteWithMorganStanleyMember" unitRef="U001" decimals="-5" scale="6" format="ixt:numdotdecimal">12.5</ix:nonFraction> million under the agreement and subsequently terminated the agreement.</div>
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<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">F-<span>28</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;">Research and Development and Manufacturing 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 July 2017, we purchased the building that houses our primary R&amp;D facility for $<ix:nonFraction name="us-gaap:PaymentsToAcquireBuildings" id="Fact_4a0c024b965c4f51b897f9cf5bc80424" contextRef="c20170701to20170731_PropertyPlantAndEquipmentByTypeAxis_PrimaryResearchAndDevelopmentFacilityMember" unitRef="U001" decimals="-5" scale="6" format="ixt:numdotdecimal">79.4</ix:nonFraction> million and our manufacturing facility for $<ix:nonFraction name="us-gaap:PaymentsToAcquireBuildings" id="Fact_06974c574f644e5baacbd3f8e2c599a6" contextRef="c20170701to20170731_PropertyPlantAndEquipmentByTypeAxis_ManufacturingFacilityMember" unitRef="U001" decimals="-5" scale="6" format="ixt:numdotdecimal">14.0</ix:nonFraction> million. We financed the purchase of these <ix:nonFraction name="ions:NumberOfPurchasedFacilitiesFinancedWithMortgageDebt" id="Fact_802514d6121f4f3ca8efa9133eb869cd" contextRef="c20150701to20150731" unitRef="U010" decimals="INF" scale="0" format="ixt-sec:numwordsen">two</ix:nonFraction> facilities with mortgage debt of $<ix:nonFraction name="us-gaap:DebtInstrumentFaceAmount" id="Fact_1c1b0d341f0d4a39b8dd7164eab2e39d" contextRef="c20170731_DebtInstrumentAxis_LongTermMortgageDebtMember" unitRef="U001" decimals="-5" scale="6" format="ixt:numdotdecimal">60.4</ix:nonFraction> million in total. Our primary R&amp;D facility mortgage has an interest rate of <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_2e21e0a6347e447a8991607c0227050a" contextRef="c20170731_PropertyPlantAndEquipmentByTypeAxis_PrimaryResearchAndDevelopmentFacilityMember" unitRef="U003" decimals="4" scale="-2" format="ixt:numdotdecimal">3.88</ix:nonFraction> percent. Our manufacturing facility mortgage has an interest rate of <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_b8df62c274f14f0499a84c79aa3dd4f9" contextRef="c20170731_PropertyPlantAndEquipmentByTypeAxis_ManufacturingFacilityMember" unitRef="U003" decimals="4" scale="-2" format="ixt:numdotdecimal">4.20</ix:nonFraction> percent. During the first <ix:nonNumeric name="ions:PeriodToMakeInterestOnlyPaymentsOnMortgageLoan" id="Fact_cec9dfdd051e4462bf766547d85be9b4" contextRef="c20200101to20201231_PropertyPlantAndEquipmentByTypeAxis_ManufacturingFacilityMember" format="ixt-sec:durwordsen"><ix:nonNumeric name="ions:PeriodToMakeInterestOnlyPaymentsOnMortgageLoan" id="Fact_885a5330a5d64c1ca25849873c2df457" contextRef="c20200101to20201231_PropertyPlantAndEquipmentByTypeAxis_PrimaryResearchAndDevelopmentFacilityMember" format="ixt-sec:durwordsen">five years</ix:nonNumeric></ix:nonNumeric> of both mortgages, we are only required to make interest payments. Both mortgages mature in August 2027.</div>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Maturity Schedules</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Annual debt and other obligation maturities, including fixed and determinable interest, at December 31, 2020 are as follows (in thousands):</div>
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<table cellpadding="0" cellspacing="0" id="z4c8baa70053148028f3836d3d205e2fe" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <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;">2021</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ContractualObligationDueInNextTwelveMonths" id="Fact_d2eb54062a6d4f188ef1dbae3b8653d3" contextRef="c20201231" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">329,189</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#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;">2022</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ContractualObligationDueInSecondYear" id="Fact_c42e928b65cd45aa923675e567769ac7" contextRef="c20201231" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">3,495</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#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;">2023</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ContractualObligationDueInThirdYear" id="Fact_6b7eb3455bef4825bec5934f0ca8a9f2" contextRef="c20201231" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">4,180</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#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;">2024</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ContractualObligationDueInFourthYear" id="Fact_5163088d8dfb4bd8afb6a945c3e15b83" contextRef="c20201231" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">553,006</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#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;">2025</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ContractualObligationDueInFifthYear" id="Fact_04194527fb664e52a3ac79595e34b654" contextRef="c20201231" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">3,494</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#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 colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ContractualObligationDueAfterFifthYear" id="Fact_74f3f2a83bb64af5b0b4b21df7d35ef0" contextRef="c20201231" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">60,933</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#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;">Subtotal</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ContractualObligation" id="Fact_41f58f8c96774a38af7b7c1cc41eabb9" contextRef="c20201231" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">954,297</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#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</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:LongTermDebtAndCapitalLeaseObligationsCurrent" id="Fact_6f4d80245c92479cb52c2337f5f2441b" contextRef="c20201231" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">300,462</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;"><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: 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 colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:InterestPayableCurrentAndNoncurrent" id="Fact_53dcce35c24c453fbe6ca8ac55743624" contextRef="c20201231" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">21,758</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;"><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%;"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Less: unamortized portion of debt discount</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:DebtInstrumentUnamortizedDiscount" id="Fact_dd49b690e0844ab6ae886462d160f033" contextRef="c20201231" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">101,820</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;"><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: debt issuance costs</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:DeferredFinanceCostsNet" id="Fact_5d2685dc1c244e588fcf3a22780fcf87" contextRef="c20201231" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">8,455</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;"><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;">Plus: lease liabilities</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DeferredRentCredit" id="Fact_59ceb438da8a4afa9f9b8d13af3dfa2f" contextRef="c20201231" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">17,310</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 88%; padding-bottom: 4px; background-color: #CCEEFF;"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total long-term debt</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:LongTermDebtAndCapitalLeaseObligations" id="Fact_e4222f3c3fbf48189f3454e1d53ce42c" contextRef="c20201231" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">539,112</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
</table>
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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Operating Leases</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Carlsbad Leases</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We lease a facility adjacent to our manufacturing facility that has laboratory and office space that we use to support our manufacturing facility. We lease this space under a non-cancelable operating lease. In May 2020, we exercised our option to extend our lease, extending our lease term from June 2021 to August 2026. We have <ix:nonFraction name="ions:LesseeLeasingArrangementsOperatingLeasesNumberOfOptionsToExtendLease" id="Fact_6447ecbf2d3b4dde91a4dfca391e39c1" contextRef="c20200101to20201231_GeographicDistributionAxis_CarlsbadFacilityMember" unitRef="U011" 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_3fa1c2318c4d4b2f8088992fbf02bb6d" contextRef="c20201231_GeographicDistributionAxis_CarlsbadFacilityMember" format="ixt-sec:durwordsen">five-year</ix:nonNumeric> period.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We also lease additional office spaces in Carlsbad. We lease these spaces under non-cancelable operating leases with initial terms ending in 2023 with options to extend each of the leases for <ix:nonFraction name="ions:LesseeLeasingArrangementsOperatingLeasesNumberOfOptionsToExtendLease" id="Fact_cb77855b95994f0488becac7637cd2b1" contextRef="c20200101to20201231_GeographicDistributionAxis_CarlsbadOfficeSpacesMember" unitRef="U011" decimals="INF" scale="0" format="ixt-sec:numwordsen">one</ix:nonFraction>&#xA0;<ix:nonNumeric name="us-gaap:LesseeOperatingLeaseRenewalTerm" id="Fact_5cb70db62bdc4486992b4feba32be9c4" contextRef="c20201231_GeographicDistributionAxis_CarlsbadOfficeSpacesMember" 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; font-style: italic;">Boston Lease</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 in the second quarter of 2018. The lease commencement date was in August 2018 and we took occupancy in September 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="c20201231_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember_GeographicDistributionAxis_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_a817cf4e10ab4fdc88a9eaaa0d2f61a5" contextRef="c20201231_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember_GeographicDistributionAxis_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="c20200101to20201231_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember_GeographicDistributionAxis_BostonOfficeSpaceMember" format="ixt-sec:durwordsen">three-month</ix:nonNumeric> free rent period, which commenced on August 15, 2018, and a tenant improvement allowance up to $<ix:nonFraction name="ions:LesseeOperatingLeaseAllowanceForTenantImprovements" id="Fact_4d5ed2a157b248b29eab88a7bb6399b9" contextRef="c20201231_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember_GeographicDistributionAxis_BostonOfficeSpaceMember" unitRef="U001" decimals="-5" scale="6" format="ixt:numdotdecimal">3.8</ix:nonFraction> million. We provided the lessor with a letter of credit to secure its obligations under the lease in the initial amount of $<ix:nonFraction name="ions:LesseeOperatingLeaseInitialLetterOfCreditToSecureLeaseObligation" id="Fact_4ea76f481ee94befba9ffed4fb541c89" contextRef="c20201231_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember_GeographicDistributionAxis_BostonOfficeSpaceMember" unitRef="U001" decimals="-5" scale="6" format="ixt:numdotdecimal">2.4</ix:nonFraction> million, to be reduced to $<ix:nonFraction name="ions:LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnThirdAnniversaryOfRentCommencementDate" id="Fact_5cd8770ef41646968466e8170f8df26c" contextRef="c20201231_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember_GeographicDistributionAxis_BostonOfficeSpaceMember" unitRef="U001" decimals="-5" scale="6" format="ixt:numdotdecimal">1.8</ix:nonFraction> million on the third anniversary of the rent commencement date and to $<ix:nonFraction name="ions:LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnFifthAnniversaryOfRentCommencementDate" id="Fact_1ff3895264114d1abecd3d9873549a39" contextRef="c20201231_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember_GeographicDistributionAxis_BostonOfficeSpaceMember" unitRef="U001" decimals="-5" scale="6" format="ixt:numdotdecimal">1.2</ix:nonFraction> million on the fifth anniversary of the rent commencement date if we meet certain conditions set forth in the lease at each such time.</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.</div>
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<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">F-<span>29</span></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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<table cellpadding="0" cellspacing="0" id="z0a8a9123d7d24adcb53d3ae530505e1b" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <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;"></div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">At December 31, 2020</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#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;">Right-of-use operating lease assets (1)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OperatingLeaseRightOfUseAsset" id="Fact_23749203f9514c17a3eb9047effcbc3f" contextRef="c20201231" unitRef="U001" decimals="-5" scale="6" format="ixt:numdotdecimal">13.1</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
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    <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;">Operating lease liabilities (2)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OperatingLeaseLiability" id="Fact_0bcc1def02bf4a9fae57dfb5f4021412" contextRef="c20201231" unitRef="U001" decimals="-5" scale="6" format="ixt:numdotdecimal">17.3</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
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    <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 colspan="1" valign="bottom" style="vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; background-color: #CCEEFF;"><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="c20201231" format="ixt-sec:duryear">7.2</ix:nonNumeric> years</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
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    <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 colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OperatingLeaseWeightedAverageDiscountRatePercent" id="Fact_0f6726aa9c174130a3010b4dad4799ef" contextRef="c20201231" unitRef="U003" decimals="3" scale="-2" format="ixt:numdotdecimal">7.0</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
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<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="z73aea46a179a456ab91ef0c8e323ab62">
  <tr>
    <td style="width: 36pt; vertical-align: top; align: right; 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_15f376e9d49947e4aed1aef14d199172" footnoteRole="http://www.xbrl.org/2003/role/footnote" xml:lang="en-US" continuedAt="Foot_bd5a3aefa9c94ed090f8085b9573c9351">Included in <span style="-sec-ix-hidden:Fact_f81ca57385a04657b8ecd0f06d505159">deposits and other assets</span></ix:footnote><ix:continuation id="Foot_bd5a3aefa9c94ed090f8085b9573c9351"> on our consolidated balance sheet.</ix:continuation></div></td>
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<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="zd0fe2a08d108427ab40244fed97b9a07">
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    <td style="width: 36pt; vertical-align: top; align: right; 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_e2e8d94790c647a9a64e7b8a949e611c" footnoteRole="http://www.xbrl.org/2003/role/footnote" xml:lang="en-US" continuedAt="Foot_b6beee0df78b493f880cb00af95e5efa1">Current portion of $<ix:nonFraction name="us-gaap:OperatingLeaseLiabilityCurrent" id="Fact_9b0c762d64a740078d7920512d9fd9e9" contextRef="c20201231" unitRef="U001" decimals="-5" scale="6" format="ixt:numdotdecimal">2.0</ix:nonFraction></ix:footnote><ix:continuation id="Foot_b6beee0df78b493f880cb00af95e5efa1" continuedAt="Foot_b6beee0df78b493f880cb00af95e5efa2"> million was included in <span style="-sec-ix-hidden:Fact_530181678e9244af8b37885d3ba85980">current portion of long-term obligations</span></ix:continuation><ix:continuation id="Foot_b6beee0df78b493f880cb00af95e5efa2" continuedAt="Foot_b6beee0df78b493f880cb00af95e5efa3"> on our consolidated balance sheet, with the difference included in <span style="-sec-ix-hidden:Fact_9c37cb3853f74a4f821bbe4ed37a06ba">long-term obligations</span></ix:continuation><ix:continuation id="Foot_b6beee0df78b493f880cb00af95e5efa3">.</ix:continuation></div></td>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">During the years ended December 31, 2020, 2019, and 2018 we paid $<ix:nonFraction name="us-gaap:OperatingLeasePayments" id="Fact_826cead5743b4e90a9d8b807e97fe422" contextRef="c20200101to20201231" unitRef="U001" decimals="-5" scale="6" format="ixt:numdotdecimal">3.8</ix:nonFraction> million, $<ix:nonFraction name="us-gaap:OperatingLeasePayments" id="Fact_297fcce7f2e44b348fe63e7be360cf7c" contextRef="c20190101to20191231" unitRef="U001" decimals="-5" scale="6" format="ixt:numdotdecimal">3.9</ix:nonFraction> million and $<ix:nonFraction name="us-gaap:OperatingLeasePayments" id="Fact_50e928616e964a8c94f28d1e4409995c" contextRef="c20180101to20181231" unitRef="U001" decimals="-5" scale="6" format="ixt:numdotdecimal">1.7</ix:nonFraction> million of lease payments, which were included in operating activities in our consolidated statement of cash flows.</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, 2020, the future payments for our operating lease liabilities are as follows (in thousands):</div>
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    <td valign="bottom" style="vertical-align: bottom; width: 88%;"><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>
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  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Less:</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 88%; padding-bottom: 2px;"><div style="text-align: left; margin-left: 18.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Imputed interest</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
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  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 88%; padding-bottom: 4px; background-color: #CCEEFF;"><div style="text-align: left; margin-left: 36.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total operating lease liabilities</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
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<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="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_c4dae47efc26426db76344c3495d0867" contextRef="c20200101to20201231" unitRef="U001" decimals="-5" scale="6" format="ixt:numdotdecimal">3.7</ix:nonFraction> million, $<ix:nonFraction name="us-gaap:OperatingLeaseExpense" id="Fact_3fece8ea1f464d25a5ccc06fa0fb6da2" contextRef="c20190101to20191231" unitRef="U001" decimals="-5" scale="6" format="ixt:numdotdecimal">3.6</ix:nonFraction> million and $<ix:nonFraction name="us-gaap:OperatingLeaseExpense" id="Fact_aa216fc8e41f4f6586b6e1b074494d8d" contextRef="c20180101to20181231" unitRef="U001" decimals="-5" scale="6" format="ixt:numdotdecimal">2.6</ix:nonFraction> million for the years ended December 31, 2020, 2019 and 2018, respectively. </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;">4. 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="c20201231_StatementClassOfStockAxis_PreferredStockMember" unitRef="U002" decimals="-6" scale="6" format="ixt:numdotdecimal">15</ix:nonFraction> million shares of &#8220;blank check&#8221; Preferred Stock. As of December 31, 2020, there were <ix:nonFraction name="us-gaap:PreferredStockSharesOutstanding" id="Fact_9e3c83d35b1a4ad9bb5804db20a70950" contextRef="c20201231_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="c20201231_StatementClassOfStockAxis_SeriesCPreferredStockMember" unitRef="U002" decimals="INF" scale="0" format="ixt-sec:numwordsen"><ix:nonFraction name="us-gaap:PreferredStockSharesIssued" id="Fact_5fe1b66991274e8cbc8b7286eae05354" contextRef="c20201231_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, 2020.</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><br /></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, 2020 and 2019, we had <ix:nonFraction name="us-gaap:CommonStockSharesAuthorized" id="Fact_292edcba897f40209ed42c14feed0f2e" contextRef="c20191231_StatementClassOfStockAxis_CommonStockMember" unitRef="U002" decimals="-6" scale="6" format="ixt:numdotdecimal"><ix:nonFraction name="us-gaap:CommonStockSharesAuthorized" id="Fact_10c668f50b664401a30c1bb6a51edb5a" contextRef="c20201231_StatementClassOfStockAxis_CommonStockMember" unitRef="U002" decimals="-6" scale="6" format="ixt:numdotdecimal">300</ix:nonFraction></ix:nonFraction> million shares of common stock authorized, of which <ix:nonFraction name="us-gaap:CommonStockSharesOutstanding" id="Fact_6d69412111c94f649e3bc6185a645456" contextRef="c20201231_StatementClassOfStockAxis_CommonStockMember" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal"><ix:nonFraction name="us-gaap:CommonStockSharesIssued" id="Fact_5f23b4a620974ffa9ac1338867c08a09" contextRef="c20201231_StatementClassOfStockAxis_CommonStockMember" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">140.4</ix:nonFraction></ix:nonFraction> million and <ix:nonFraction name="us-gaap:CommonStockSharesOutstanding" id="Fact_eba69077d17e4204b64b00ee384f8ab0" contextRef="c20191231_StatementClassOfStockAxis_CommonStockMember" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal"><ix:nonFraction name="us-gaap:CommonStockSharesIssued" id="Fact_7461dbbf5e58485bbd613618075e0ee5" contextRef="c20191231_StatementClassOfStockAxis_CommonStockMember" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">140.3</ix:nonFraction></ix:nonFraction> million were issued and outstanding, respectively. As of December 31, 2020, total common shares reserved for future issuance were <ix:nonFraction name="us-gaap:CommonStockCapitalSharesReservedForFutureIssuance" id="Fact_47e88bfdb1664c48a2b1ff64f80389f5" contextRef="c20201231_StatementClassOfStockAxis_CommonStockMember" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">26.1</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, 2020, 2019 and 2018, we issued <ix:nonFraction name="us-gaap:StockIssuedDuringPeriodSharesShareBasedCompensationGross" id="Fact_0ee4b00a77834001bc604428d95159c5" contextRef="c20200101to20201231_StatementClassOfStockAxis_CommonStockMember" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">1.7</ix:nonFraction> million, <ix:nonFraction name="us-gaap:StockIssuedDuringPeriodSharesShareBasedCompensationGross" id="Fact_6d8eb059ce834187b603ca07d5abb207" contextRef="c20190101to20191231_StatementClassOfStockAxis_CommonStockMember" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">3.1</ix:nonFraction> million and <ix:nonFraction name="us-gaap:StockIssuedDuringPeriodSharesShareBasedCompensationGross" id="Fact_edd10ce23a74492e8176afb94a7abdb0" contextRef="c20180101to20181231_StatementClassOfStockAxis_CommonStockMember" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">1.5</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="c20200101to20201231_StatementClassOfStockAxis_CommonStockMember" unitRef="U001" decimals="-5" scale="6" format="ixt:numdotdecimal">52.0</ix:nonFraction> million, $<ix:nonFraction name="us-gaap:ProceedsFromIssuanceOfSharesUnderIncentiveAndShareBasedCompensationPlansIncludingStockOptions" id="Fact_5fbad294b6304ae4a8a72a7d07384a09" contextRef="c20190101to20191231_StatementClassOfStockAxis_CommonStockMember" unitRef="U001" decimals="-5" scale="6" format="ixt:numdotdecimal">119.7</ix:nonFraction> million and $<ix:nonFraction name="us-gaap:ProceedsFromIssuanceOfSharesUnderIncentiveAndShareBasedCompensationPlansIncludingStockOptions" id="Fact_4af5fbc849034e59b7d2901adc45af29" contextRef="c20180101to20181231_StatementClassOfStockAxis_CommonStockMember" unitRef="U001" decimals="-5" scale="6" format="ixt:numdotdecimal">27.9</ix:nonFraction> million in 2020, 2019 and 2018, respectively.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In September 2019, our board of directors approved a share repurchase program of up to $<ix:nonFraction name="us-gaap:StockRepurchaseProgramAuthorizedAmount1" id="Fact_44310671d1664bfca3445b963a157027" contextRef="c20190930" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">125</ix:nonFraction> million of our common stock. In 2019, we repurchased <ix:nonFraction name="us-gaap:StockRepurchasedDuringPeriodShares" id="Fact_a0ec8c80989241c28567434e9da68f95" contextRef="c20190101to20191231" unitRef="U002" decimals="0" scale="0" format="ixt:numdotdecimal">535,000</ix:nonFraction> shares for $<ix:nonFraction name="us-gaap:PaymentsForRepurchaseOfCommonStock" id="Fact_b3c70b4e95ca4205b78bd5e2e50aeeab" contextRef="c20190101to20191231" unitRef="U001" decimals="-5" scale="6" format="ixt:numdotdecimal">34.4</ix:nonFraction> million. In the first quarter of 2020, we repurchased an additional <ix:nonFraction name="us-gaap:StockRepurchasedDuringPeriodShares" id="Fact_e459a3912815439c8077106b57fb5880" contextRef="c20200101to20200331" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">1.5</ix:nonFraction> million shares for $<ix:nonFraction name="us-gaap:PaymentsForRepurchaseOfCommonStock" id="Fact_2b769cf5ebe543ef91ba7139fec3a4d2" contextRef="c20200101to20200331" unitRef="U001" decimals="-5" scale="6" format="ixt:numdotdecimal">90.5</ix:nonFraction> million.</div>
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<div style="text-align: justify; 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 June 1989, our Board of Directors adopted, and the stockholders subsequently approved, a stock option plan that, as amended, provides for the issuance of non-qualified and incentive stock options for the purchase of up to <ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAuthorized" id="Fact_2a82263b39a7474ba2b3298ff2f3a349" contextRef="c20201231_PlanNameAxis_StockOptionPlan1989Member" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">20.0</ix:nonFraction> million shares of common stock to our employees, directors, and consultants. The plan expires in January 2024. The 1989 Plan does not allow us to grant stock bonuses or restricted stock awards and prohibits us from repricing any options outstanding under the plan unless our stockholders approve the repricing. Options vest over a <ix:nonNumeric name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1" id="Fact_300b6e73bf984f4ba7b411e09fd8ac0a" contextRef="c20200101to20201231_AwardTypeAxis_StockOptionMember_PlanNameAxis_StockOptionPlan1989Member" format="ixt-sec:durwordsen">four-year</ix:nonNumeric> period, with <ix:nonFraction name="us-gaap:SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage" id="Fact_f9de77fe0ed4406e89bc6cca403c951f" contextRef="c20200101to20201231_AwardTypeAxis_StockOptionMember_PlanNameAxis_StockOptionPlan1989Member_VestingAxis_ShareBasedCompensationAwardTrancheOneMember" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">25</ix:nonFraction>percent exercisable at the end of <ix:nonNumeric name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardRequisiteServicePeriod1" id="Fact_8c42e3e31eb04afc9a1a6d089d774313" contextRef="c20200101to20201231_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="c20200101to20201231_AwardTypeAxis_StockOptionMember_PlanNameAxis_StockOptionPlan1989Member" format="ixt-sec:durwordsen">seven years</ix:nonNumeric>. At December 31, 2020, a total of <ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber" id="Fact_add8de5b32ae49bb87473e4eddedffb6" contextRef="c20201231_PlanNameAxis_StockOptionPlan1989Member" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">30</ix:nonFraction> thousand options were outstanding, of which options to purchase <ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisableNumber" id="Fact_803cbfb1dea74d34930f47cade7a9b19" contextRef="c20201231_PlanNameAxis_StockOptionPlan1989Member" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">30</ix:nonFraction> thousand shares were exercisable, and <ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAvailableForGrant" id="Fact_8c931ba74e0d4e5c8d57ed4b294c4a22" contextRef="c20201231_PlanNameAxis_StockOptionPlan1989Member" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">50</ix:nonFraction> thousand shares were available for future grant under the 1989 Plan.</div>
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<div style="text-align: justify; text-indent: -18pt; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">2011 Equity Incentive Plan</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In March 2011, our Board of Directors adopted, and the stockholders subsequently approved, a stock option plan that provides for the issuance of stock options, stock appreciation rights, restricted stock awards, restricted stock unit awards, and performance cash awards to our employees, directors, and consultants. In June 2015, May 2017 and June 2019, after receiving approval from our stockholders, we amended our 2011 Equity Incentive Plan 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:numdotdecimal">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:numdotdecimal">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:numdotdecimal">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:numdotdecimal">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:numdotdecimal">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:numdotdecimal">23.0</ix:nonFraction> million in June 2019. 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 options and restricted stock unit awards to our employees, directors and consultants. 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="c20200101to20201231_AwardTypeAxis_RestrictedStockUnitsRSUMember_PlanNameAxis_EquityIncentivePlan2011Member" format="ixt-sec:durwordsen">four-year</ix:nonNumeric> period. At December 31, 2020, a total of <ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber" id="Fact_f6eb4ef69d9549b79f43b5ca7f3d3f65" contextRef="c20201231_PlanNameAxis_EquityIncentivePlan2011Member" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">11.4</ix:nonFraction> million options were outstanding, of which <ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisableNumber" id="Fact_c37dd0f781d649a5bc97d2c87bbaeacf" contextRef="c20201231_PlanNameAxis_EquityIncentivePlan2011Member" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">6.7</ix:nonFraction> million were exercisable, <ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardNonOptionEquityInstrumentsOutstandingNumber" id="Fact_f19dff70c85e4b53ab5b44f7e4b872f2" contextRef="c20201231_AwardTypeAxis_RestrictedStockUnitsRSUMember_PlanNameAxis_EquityIncentivePlan2011Member" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">2.2</ix:nonFraction> million restricted stock unit awards were outstanding, and <ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAvailableForGrant" id="Fact_f121d278af9942b4ba6d23912dbef6db" contextRef="c20201231_PlanNameAxis_EquityIncentivePlan2011Member" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">4.3</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. The stock options and restricted stock unit awards we issued to Dr. Stanley T. Crooke in his former role as chief executive officer and certain stock options and restricted stock unit awards we issued to B. Lynne Parshall in her former role as chief operating officer will accelerate upon a change of control, as defined in the 2011 Plan. 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. If we terminate <ix:nonFraction name="ions:NumberOfExecutiveOfficersTerminatedBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers" id="Fact_8f959a059fb340fc9f6dfdc4cbdfc6d9" contextRef="c20200101to20201231_PlanNameAxis_EquityIncentivePlan2011Member" unitRef="U012" decimals="INF" scale="0" format="ixt-sec:numwordsen">one</ix:nonFraction> of our executive officers or if an executive officer resigns for good reason during the period that begins <ix:nonNumeric name="ions:PeriodBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers" id="Fact_5cf8f8a57af249d4a6cce115597f8861" contextRef="c20200101to20201231_PlanNameAxis_EquityIncentivePlan2011Member" format="ixt-sec:durwordsen">three months</ix:nonNumeric> before and ends <ix:nonNumeric name="ions:PeriodAfterChangeInControlWhenVestingWillAccelerateForExecutiveOfficers" id="Fact_4b4db5c64d7f42eca6f341535cd62db4" contextRef="c20200101to20201231_PlanNameAxis_EquityIncentivePlan2011Member" format="ixt-sec:durwordsen">twelve months</ix:nonNumeric> following a change in control of the company, the impacted executive officers&#8217; 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: 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 Acquisition in October 2020, we assumed the unallocated portion of the available share reserve under the Akcea 2015 Equity Incentive Plan. In December 2020, we amended and restated the Akcea 2015 equity plan, including renaming the plan as the Ionis Pharmaceuticals, Inc. 2020 Equity Incentive Plan, or 2020 Plan. The 2020 Plan provided for the issuance of up to </span><ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAuthorized" id="Fact_c2fdd0b5f17c4a559deafa59528e79eb" contextRef="c20201231_PlanNameAxis_EquityIncentivePlan2020Member" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">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 Acquisition.</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 options and restricted stock unit awards to our eligible employees, directors and consultants. We have granted stock options to our employees under the 2020 Plan which vest annually over a <ix:nonNumeric name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1" id="Fact_f1c93af494b04abea846be47da9b6f21" contextRef="c20200101to20201231_AwardTypeAxis_StockOptionMember_PlanNameAxis_EquityIncentivePlan2020Member" format="ixt-sec:durwordsen">four-year</ix:nonNumeric> period. At December 31, 2020, a total of <ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber" id="Fact_7b23f3391b8648699d7f9d9bdfc98ad2" contextRef="c20201231_PlanNameAxis_EquityIncentivePlan2020Member" unitRef="U002" decimals="-4" scale="6" format="ixt:numdotdecimal">0.01</ix:nonFraction> million options were outstanding, of which <ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisableNumber" id="Fact_4795c74284de4082b785b01a78026eb7" contextRef="c20201231_PlanNameAxis_EquityIncentivePlan2020Member" unitRef="U002" decimals="INF" scale="0" format="ixt-sec:numwordsen">none</ix:nonFraction> were exercisable, and <ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAvailableForGrant" id="Fact_445e0eb67023409bac8ed8d6e705c2d6" contextRef="c20201231_PlanNameAxis_EquityIncentivePlan2020Member" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">2.6</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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    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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>
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<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="z5ac0a33cd456453795b7a6dee28dcaac">
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    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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>
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    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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>
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<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="z52630d9833314cd2b584bf1e2514e71e">
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    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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>
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    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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>
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    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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>
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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;">2002 Non-Employee Directors&#8217; Stock Option Plan</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In September 2001, our Board of Directors adopted, and the stockholders subsequently approved, an amendment and restatement of the 1992 Non-Employee Directors&#8217; Stock Option Plan, which provides for the issuance of non-qualified stock options and restricted stock units to our non-employee directors. The name of the resulting plan is the 2002 Non-Employee Directors&#8217; Stock Option Plan, or the 2002 Plan. In June 2015, after receiving approval from our stockholders, we amended our 2002 Plan to increase the total number of shares reserved for issuance from <ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAuthorized" id="Fact_0e9dea3a9bb44f258d4a6a1eeffbb1b0" contextRef="c20150531_PlanNameAxis_NonemployeeDirectorsStockOptionPlan2002Member" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">1.2</ix:nonFraction> million to <ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAuthorized" id="Fact_e55c20e37dc6464eb74bde99a3d220dc" contextRef="c20150630_PlanNameAxis_NonemployeeDirectorsStockOptionPlan2002Member" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">2.0</ix:nonFraction> million. In June 2020, after receiving approval from our stockholders, we further amended our 2002 Plan. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">The amendments included:</span></div>
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<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="z5e4f865f85114d45a89e7bb61564e0e0">
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    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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 </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">increase to the total number of shares reserved for issuance under the plan from </span><ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAuthorized" id="Fact_fda3670487384cb49c8eb41d6d8f4665" contextRef="c20150630_PlanNameAxis_NonemployeeDirectorsStockOptionPlan2002Member" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">2.0</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million to </span><ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAuthorized" id="Fact_8b16c9fcbd8a4de6a3ff40e97438a3a8" contextRef="c20200630_PlanNameAxis_NonemployeeDirectorsStockOptionPlan2002Member" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">2.8</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million shares;</span></div></td>
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<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="z920b1672958340049e91b73e544ffb88">
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    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">A reduction to the amount of the automatic awards under the plan;</div></td>
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<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="z9dc5c7c10f39451a90ae42ff5d29e107">
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    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">A revision to the vesting schedule of new awards granted; and</div></td>
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<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="z2ecc905910434dea959a202548f8b597">
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    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">An extension of the term of the plan.</div></td>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Options under this plan expire <ix:nonNumeric name="us-gaap:SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod" id="Fact_e6b00753880241348e596a82fa22bab2" contextRef="c20200101to20201231_AwardTypeAxis_StockOptionMember_PlanNameAxis_NonemployeeDirectorsStockOptionPlan2002Member" format="ixt-sec:durwordsen">10 years</ix:nonNumeric> from the date of grant. At December 31, 2020, a total of <ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber" id="Fact_28beff5bd3d14e0c9936c3a0e4bfd184" contextRef="c20201231_PlanNameAxis_NonemployeeDirectorsStockOptionPlan2002Member" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">1.0</ix:nonFraction> million options were outstanding, of which <ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisableNumber" id="Fact_5c3c554e640546a481c2968b37014870" contextRef="c20201231_PlanNameAxis_NonemployeeDirectorsStockOptionPlan2002Member" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">0.6</ix:nonFraction> million were exercisable, <ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardNonOptionEquityInstrumentsOutstandingNumber" id="Fact_d025b834777346cfa313dfb503dafd03" contextRef="c20201231_AwardTypeAxis_RestrictedStockUnitsRSUMember_PlanNameAxis_NonemployeeDirectorsStockOptionPlan2002Member" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">0.1</ix:nonFraction> million restricted stock unit awards were outstanding, and <ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAvailableForGrant" id="Fact_03da27efb55141628520731fb9e70ab8" contextRef="c20201231_PlanNameAxis_NonemployeeDirectorsStockOptionPlan2002Member" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">0.8</ix:nonFraction> million shares were available for future grant under the 2002 Plan.</div>
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<div style="text-align: justify; text-indent: -18pt; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Employee Stock Purchase Plan</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In June 2009, our Board of Directors adopted, and the stockholders subsequently approved, the amendment and restatement of the ESPP and we reserved an additional <ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfAdditionalSharesAuthorized" id="Fact_3b40f4cda8e040fdba6be624573711c9" contextRef="c20090601to20090630_PlanNameAxis_EmployeeStockPurchasePlanMember" unitRef="U002" decimals="0" scale="0" format="ixt:numdotdecimal">150,000</ix:nonFraction> shares of common stock for issuance thereunder. In each of the subsequent years until 2019, we reserved an additional <ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfAdditionalSharesAuthorized" id="Fact_627f300828104f14b873bf05eda50f67" contextRef="c20200101to20201231_PlanNameAxis_EmployeeStockPurchasePlanMember" unitRef="U002" decimals="0" scale="0" format="ixt:numdotdecimal">150,000</ix:nonFraction> shares of common stock for the ESPP resulting in a total of <ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAuthorized" id="Fact_e19efe7ddb5143df982e961a832ee9c5" contextRef="c20201231_PlanNameAxis_EmployeeStockPurchasePlanMember" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">3.2</ix:nonFraction> million shares authorized under the plan as of December 31, 2020. The ESPP permits full-time employees to purchase common stock through payroll deductions (which cannot exceed <ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardMaximumEmployeeSubscriptionRate" id="Fact_ad7d5d970b7445cb891d0cfb579417b5" contextRef="c20201231_PlanNameAxis_EmployeeStockPurchasePlanMember" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">10</ix:nonFraction>percent of each employee&#8217;s compensation) at the lower of <ix:nonFraction name="us-gaap:SharebasedCompensationArrangementBySharebasedPaymentAwardPurchasePriceOfCommonStockPercent" id="Fact_f1124fb149ea4ba28036505d69fad8f3" contextRef="c20200101to20201231_PlanNameAxis_EmployeeStockPurchasePlanMember" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">85</ix:nonFraction>percent of fair market value at the beginning of the purchase period or the end of each purchase period. Under the amended and restated ESPP, employees must hold the stock they purchase for a minimum of <ix:nonNumeric name="ions:ShareBasedCompensationArrangementByShareBasedPaymentAwardHoldingPeriod" id="Fact_f085e44a32534bbd8486ce10fc828657" contextRef="c20200101to20201231_PlanNameAxis_EmployeeStockPurchasePlanMember" format="ixt-sec:durwordsen">six months</ix:nonNumeric> from the date of purchase. During 2020, employees purchased and we issued to employees <ix:nonFraction name="us-gaap:StockIssuedDuringPeriodSharesEmployeeStockPurchasePlans" id="Fact_36267c2abcb644b69eb45aceda22f69b" contextRef="c20200101to20201231_PlanNameAxis_EmployeeStockPurchasePlanMember" unitRef="U002" decimals="-4" scale="6" format="ixt:numdotdecimal">0.06</ix:nonFraction> million shares under the ESPP at a weighted average price of $<ix:nonFraction name="ions:EmployeeStockPurchasePlanWeightedAverageSalesPriceOfSharesPurchased" id="Fact_2c284719dc094a59851d962ad33aacae" contextRef="c20200101to20201231_PlanNameAxis_EmployeeStockPurchasePlanMember" unitRef="U004" decimals="2" scale="0" format="ixt:numdotdecimal">43.65</ix:nonFraction> per share. At December 31, 2020, there were <ix:nonFraction name="ions:EmployeeStockPurchasePlanSharesAvailableForPurchase" id="Fact_9bcf03b844ab41c1a8fbd64333e01f0e" contextRef="c20201231_PlanNameAxis_EmployeeStockPurchasePlanMember" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">0.7</ix:nonFraction> million shares available for purchase under the ESPP.</div>
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<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">F-<span>32</span></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="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, 2020 (in thousands, except per share and contractual life data):</div>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#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;">The weighted-average estimated fair values of options granted were $<ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue" id="Fact_bd436c790ccc47e68cd7e2153d0e63dd" contextRef="c20200101to20201231_AwardTypeAxis_StockOptionMember" unitRef="U004" decimals="2" scale="0" format="ixt:numdotdecimal">29.43</ix:nonFraction>, $<ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue" id="Fact_4dd2a593ab554175bbb0a93d55390a88" contextRef="c20190101to20191231_AwardTypeAxis_StockOptionMember" unitRef="U004" decimals="2" scale="0" format="ixt:numdotdecimal">28.76</ix:nonFraction> and $<ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue" id="Fact_a3befa246b7c4d03aced2b483085120f" contextRef="c20180101to20181231_AwardTypeAxis_StockOptionMember" unitRef="U004" decimals="2" scale="0" format="ixt:numdotdecimal">25.49</ix:nonFraction> for the years ended December 31, 2020, 2019 and 2018, respectively. The total intrinsic value of options exercised during the years ended December 31, 2020, 2019 and 2018 were $<ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisesInPeriodTotalIntrinsicValue" id="Fact_1218d40eea68418bb4f00f1ad78f4cff" contextRef="c20200101to20201231_AwardTypeAxis_StockOptionMember" unitRef="U001" decimals="-5" scale="6" format="ixt:numdotdecimal">15.5</ix:nonFraction> million, $<ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisesInPeriodTotalIntrinsicValue" id="Fact_bde2c92764604d8497b0668d13fb888b" contextRef="c20190101to20191231_AwardTypeAxis_StockOptionMember" unitRef="U001" decimals="-5" scale="6" format="ixt:numdotdecimal">83.8</ix:nonFraction> million and $<ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisesInPeriodTotalIntrinsicValue" id="Fact_8cc0e16daa8e4b2382fc554cc98ddf99" contextRef="c20180101to20181231_AwardTypeAxis_StockOptionMember" unitRef="U001" decimals="-5" scale="6" format="ixt:numdotdecimal">34.8</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="c20200101to20201231_AwardTypeAxis_StockOptionMember" unitRef="U001" decimals="-5" scale="6" format="ixt:numdotdecimal">43.7</ix:nonFraction> million, $<ix:nonFraction name="us-gaap:ProceedsFromStockOptionsExercised" id="Fact_9199ba163c904e0aaa3d539cccdda650" contextRef="c20190101to20191231_AwardTypeAxis_StockOptionMember" unitRef="U001" decimals="-5" scale="6" format="ixt:numdotdecimal">105.9</ix:nonFraction> million and $<ix:nonFraction name="us-gaap:ProceedsFromStockOptionsExercised" id="Fact_6cc972e2025849d8a6820145ab793c87" contextRef="c20180101to20181231_AwardTypeAxis_StockOptionMember" unitRef="U001" decimals="-5" scale="6" format="ixt:numdotdecimal">18.9</ix:nonFraction> million for the years ended December 31, 2020, 2019 and 2018, respectively. For the year ended December 31, 2020, the weighted-average fair value of options exercised was $<ix:nonFraction name="ions:ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisesInPeriodWeightedAverageFairValue" id="Fact_2b17593a26f3421991429bedce8b1c41" contextRef="c20200101to20201231_AwardTypeAxis_StockOptionMember" unitRef="U004" decimals="2" scale="0" format="ixt:numdotdecimal">55.33</ix:nonFraction>. As of December 31, 2020, total unrecognized compensation cost related to non-vested stock options was $<ix:nonFraction name="us-gaap:EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedStockOptions" id="Fact_72c37b7b47114b45a9abf8d6722faa52" contextRef="c20201231_AwardTypeAxis_StockOptionMember" unitRef="U001" decimals="-5" scale="6" format="ixt:numdotdecimal">54.1</ix:nonFraction> million. We expect to recognize this cost over a weighted average period of <ix:nonNumeric name="us-gaap:EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1" id="Fact_b3913cf410e541fe90a6f1003271ba18" contextRef="c20200101to20201231_AwardTypeAxis_StockOptionMember" format="ixt-sec:duryear">1.1</ix:nonNumeric> years. We will adjust the total unrecognized compensation cost for future changes in estimated forfeitures.</div>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Restricted Stock Unit Activity</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following table summarizes the RSU activity for the year ended December 31, 2020 (in thousands, except per share data):</div>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></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 /></div>
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<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">For the years ended December 31, 2020, 2019 and 2018, the weighted-average grant date fair value of RSUs granted was $<ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriodWeightedAverageGrantDateFairValue" id="Fact_6c1a06db93094900a762b6eb164c546f" contextRef="c20200101to20201231_AwardTypeAxis_RestrictedStockUnitsRSUMember" unitRef="U004" decimals="2">60.86</ix:nonFraction>, $<ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriodWeightedAverageGrantDateFairValue" id="Fact_43f43b5a78cc4be1918b46bdde39a8d8" contextRef="c20190101to20191231_AwardTypeAxis_RestrictedStockUnitsRSUMember" unitRef="U004" decimals="2" scale="0" format="ixt:numdotdecimal">60.23</ix:nonFraction> and $<ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriodWeightedAverageGrantDateFairValue" id="Fact_57cca4b8f1044664988a96c292d978d1" contextRef="c20180101to20181231_AwardTypeAxis_RestrictedStockUnitsRSUMember" unitRef="U004" decimals="2" scale="0" format="ixt:numdotdecimal">51.06</ix:nonFraction> per RSU, respectively. As of December 31, 2020, total unrecognized compensation cost related to RSUs was $<ix:nonFraction name="us-gaap:EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions" id="Fact_87ca3f2ec59f473aaf7df5ff01d27232" contextRef="c20201231_AwardTypeAxis_RestrictedStockUnitsRSUMember" unitRef="U001" decimals="-5" scale="6" format="ixt:numdotdecimal">55.3</ix:nonFraction> million. We expect to recognize this cost over a weighted average period of <ix:nonNumeric name="us-gaap:EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1" id="Fact_18e1a1c706d54df78d64da3820fb50b9" contextRef="c20200101to20201231_AwardTypeAxis_RestrictedStockUnitsRSUMember" format="ixt-sec:duryear">1.3</ix:nonNumeric> years. We will adjust the total unrecognized compensation cost for future changes in estimated forfeitures.</div>
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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Stock-based Compensation Expense and Valuation Information</div>
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<div 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, 2020, 2019 and 2018 (in thousands):</div>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;"><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-<span>33</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;">Our non-cash stock-based compensation expense included </span>$<ix:nonFraction name="us-gaap:AllocatedShareBasedCompensationExpense" id="Fact_f10b8b42e6244f988aaf4fd5de10cafc" contextRef="c20200101to20201231_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember" unitRef="U001" decimals="-5" scale="6" format="ixt:numdotdecimal">94.8</ix:nonFraction> million, $<ix:nonFraction name="us-gaap:AllocatedShareBasedCompensationExpense" id="Fact_1f1c1f94efad47beb6afa69146eccaa6" contextRef="c20190101to20191231_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember" unitRef="U001" decimals="-5" scale="6" format="ixt:numdotdecimal">37.1</ix:nonFraction> million and $<ix:nonFraction name="us-gaap:AllocatedShareBasedCompensationExpense" id="Fact_afb09cb91b5c4c60ac3218bdcff80a83" contextRef="c20180101to20181231_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember" unitRef="U001" decimals="-5" scale="6">44.3</ix:nonFraction> million <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">of stock-based compensation expense for Akcea employees for the years ended December 31, 2020, 2019 and 2018, respectively.</span></div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In October 2020, as part of the Akcea Acquisition, Akcea&#8217;s outstanding equity awards vested under Akcea&#8217;s Plan. As a result, in the fourth quarter of 2020, we recognized all unrecognized stock-based compensation ($<ix:nonFraction name="us-gaap:EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions" id="Fact_d16c0cc8629a4c07b114768b69b0edb5" contextRef="c20201031_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember" unitRef="U001" decimals="-5" scale="6" format="ixt:numdotdecimal">59.3</ix:nonFraction> million) under Akcea&#8217;s Plan. See Note 7, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Akcea Acquisition</span>, in the Notes to the Consolidated Financial Statements for further details.</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 the third quarter of 2019, </span><ix:nonFraction name="ions:NumberOfExecutiveOfficersTerminatingEmployment" id="Fact_5ae968a2633a430684e974cc63021deb" contextRef="c20190701to20190930_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember" unitRef="U012" decimals="INF" scale="0" format="ixt-sec:numwordsen">three</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> Akcea executive officers terminated their employment and entered into separation agreements with Akcea. As a result, in the third quarter of 2019, Akcea reversed $</span><ix:nonFraction name="us-gaap:AllocatedShareBasedCompensationExpense" id="Fact_911c01da068b45da87f911f97ac956aa" contextRef="c20190701to20190930_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember" unitRef="U001" decimals="-5" scale="6" sign="-" format="ixt:numdotdecimal">19.1</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million of stock-based compensation expense it had previously recognized related to the executive officers&#8217; stock options and RSUs that were no longer going to vest.</span></div>
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<div style="text-align: justify; text-indent: -18pt; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Determining Fair Value</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;">Valuation.</span> We measure stock-based compensation expense for equity-classified awards, principally related to stock options, RSUs, and stock purchase rights under the ESPP at the grant date, based on the estimated fair value of the award and we recognize the expense over the employee&#8217;s requisite service period. We value RSUs based on the market price of our common stock on the date of grant.</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. The expected term of stock options granted represents the period of time that we expect them to be outstanding. We estimate the expected term of options granted based on actual and projected exercise patterns. We recognize compensation expense for stock options granted, RSUs, 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;">For the years ended December 31, 2020, 2019 and 2018, we used the following weighted-average assumptions in our Black-Scholes calculations:</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;">Ionis Employee Stock Options:</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;">Ionis Board of Director Stock Options:</div>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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  <tr>
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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;">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>
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<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">F-<span>34</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;">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>
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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;">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>
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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;">Expected Life. </span>The expected term of stock options we have granted represents the period of time that we expect them to be outstanding. We estimated the expected term of options we have granted based on actual and projected 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;"><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>
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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 stock plans, Akcea had its own stock plan prior to the Akcea Acquisition, referred to as the Akcea 2015 Equity Incentive Plan, or Akcea Plan. Under the Akcea Plan, Akcea granted options and RSUs.</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, 2020, 2019 and 2018, we used the following weighted-average assumptions in our Black-Scholes calculations for the Akcea Plan:</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;">Akcea Employee Stock Options:</div>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom;">&#160;</td>
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<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="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following summarizes the Black-Scholes input methodology for Akcea options that differs from the methodology we use for Ionis options:</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;">Volatility.</span> Since Akcea did not have sufficient history to estimate the volatility of its common stock, Akcea calculated its expected volatility based on a blend of its historical volatility and reported data from selected publicly traded peer companies for which historical information was available.</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;">Expected Life. </span>Since Akcea did not have sufficient historical information, it used the simplified method for estimating its expected term. Under the simplified method Akcea calculated its expected term as the average time-to-vesting and the contractual life of the options.</div>
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<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">F-<span>35</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;">Akcea 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 was based on the market price of Akcea&#8217;s common stock on the date of grant. Akcea granted RSUs with various vesting terms between <ix:nonNumeric name="us-gaap:SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod" id="Fact_020993f8d1d346f49c1b4085faa28961" contextRef="c20200101to20201231_AwardTypeAxis_RestrictedStockUnitsRSUMember_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember_RangeAxis_MinimumMember" format="ixt-sec:durwordsen">six months</ix:nonNumeric> and <ix:nonNumeric name="us-gaap:SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod" id="Fact_b603680403634dd08c3d116f8a9d593d" contextRef="c20200101to20201231_AwardTypeAxis_RestrictedStockUnitsRSUMember_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember_RangeAxis_MaximumMember" format="ixt-sec:durwordsen">four years</ix:nonNumeric>. The weighted-average grant date fair value of RSUs granted to employees for years ended December 31, 2020 and 2019 was $<ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriodWeightedAverageGrantDateFairValue" id="Fact_198157585b724acab82dae20ccbe9a3b" contextRef="c20200101to20201231_AwardTypeAxis_RestrictedStockUnitsRSUMember_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember" unitRef="U004" decimals="2" scale="0" format="ixt:numdotdecimal">15.57</ix:nonFraction> and $<ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriodWeightedAverageGrantDateFairValue" id="Fact_21aa6c0c467147b8bf66d9330aae9c5b" contextRef="c20190101to20191231_AwardTypeAxis_RestrictedStockUnitsRSUMember_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember" unitRef="U004" decimals="2" scale="0" format="ixt:numdotdecimal">21.95</ix:nonFraction> per share, respectively.</div>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">5. Income Taxes</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Income (loss) before income taxes is comprised of (in thousands):</div>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
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    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2019</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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  <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>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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</ix:continuation></ix:continuation><ix:continuation id="Text_bf9a9759d58b4bcb96c70042a7a861e95" continuedAt="Text_bf9a9759d58b4bcb96c70042a7a861e96">
<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;">Our income tax expense (benefit) was as follows (in thousands):</div>
</ix:continuation></ix:nonNumeric><ix:continuation id="Text_ecf4df12593845859d91b16ab3033a911" continuedAt="Text_ecf4df12593845859d91b16ab3033a912"><ix:continuation id="Text_bf9a9759d58b4bcb96c70042a7a861e97" continuedAt="Text_bf9a9759d58b4bcb96c70042a7a861e98">
<div><br /></div>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="10" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><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 colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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  <tr>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
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  </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>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;">&#160;</td>
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  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DeferredStateAndLocalIncomeTaxExpenseBenefit" id="Fact_989cd3ae4b8346399913987c81866608" contextRef="c20190101to20191231" unitRef="U001" decimals="-3" scale="3" format="ixt:zerodash">&#8212;</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DeferredStateAndLocalIncomeTaxExpenseBenefit" id="Fact_d254df8f11b14f8594ca47e6a7f95134" contextRef="c20180101to20181231" unitRef="U001" decimals="-3" scale="3" format="ixt:zerodash">&#8212;</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
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  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total deferred income tax benefit</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DeferredIncomeTaxExpenseBenefit" id="Fact_be2ed18e2072458bba8c88d0a45981b5" contextRef="c20200101to20201231" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">313,271</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:DeferredIncomeTaxExpenseBenefit" id="Fact_499db25413694d1996ce63465160cf19" contextRef="c20190101to20191231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">7,096</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:DeferredIncomeTaxExpenseBenefit" id="Fact_b02665644bb848b5b79ed1b9b7aba937" contextRef="c20180101to20181231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">290,511</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;"><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%; 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 colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:IncomeTaxExpenseBenefit" id="Fact_39aa3556afa54b90a94840a97eb5b995" contextRef="c20200101to20201231" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">316,734</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
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</ix:continuation></ix:continuation><ix:continuation id="Text_bf9a9759d58b4bcb96c70042a7a861e99" continuedAt="Text_bf9a9759d58b4bcb96c70042a7a861e910">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br /></div>
</ix:continuation><ix:nonNumeric name="us-gaap:ScheduleOfEffectiveIncomeTaxRateReconciliationTableTextBlock" id="Text_51a6178b5d104096a200807a70958787" contextRef="c20200101to20201231" escape="true" continuedAt="Text_479f523be0134f5d8d15fa71d967c2e61"><ix:continuation id="Text_bf9a9759d58b4bcb96c70042a7a861e910" continuedAt="Text_bf9a9759d58b4bcb96c70042a7a861e911">
<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 expense (benefit) for income taxes differs from the amount computed by applying the U.S. federal statutory rate to income (loss) before taxes. The sources and tax effects of the differences are as follows (in thousands):</div>
</ix:continuation></ix:nonNumeric><ix:continuation id="Text_479f523be0134f5d8d15fa71d967c2e61" continuedAt="Text_479f523be0134f5d8d15fa71d967c2e62"><ix:continuation id="Text_bf9a9759d58b4bcb96c70042a7a861e911" continuedAt="Text_bf9a9759d58b4bcb96c70042a7a861e912">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_479f523be0134f5d8d15fa71d967c2e62"><ix:continuation id="Text_bf9a9759d58b4bcb96c70042a7a861e912" continuedAt="Text_bf9a9759d58b4bcb96c70042a7a861e913">
<table cellpadding="0" cellspacing="0" id="zcb2d6ab6c48e4c278e66d61bd2c81d98" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"></div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="22" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><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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  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="6" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2020</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="6" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2019</div></td>
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    <td colspan="6" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2018</div></td>
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  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:IncomeLossFromContinuingOperationsBeforeIncomeTaxesMinorityInterestAndIncomeLossFromEquityMethodInvestments" id="Fact_82f7c2373f9d4876bd0497532436a6c4" contextRef="c20180101to20181231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">76,156</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom;">&#160;</td>
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  <tr>
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  <tr>
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  <tr>
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  <tr>
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  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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  <tr>
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  </tr>
  <tr>
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  </tr>
  <tr>
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  </tr>
  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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  </tr>
  <tr>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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  </tr>
  <tr>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
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  </tr>
  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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  </tr>
  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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  </tr>
  <tr>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
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  </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;">Effective rate</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:EffectiveIncomeTaxRateContinuingOperations" id="Fact_f0cc7188c05e4808b694a7a38a1291cc" contextRef="c20190101to20191231" unitRef="U003" decimals="3" scale="-2" format="ixt:numdotdecimal">12.6</ix:nonFraction></div></td>
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</table>
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<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br /></div>
</ix:continuation></div>
<div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
<div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">F-<span>36</span></div>
</div>
<div style="page-break-after:always;"><hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>
<div></div>
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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>
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<div><br /></div>
</ix:continuation><ix:nonNumeric name="us-gaap:ScheduleOfDeferredTaxAssetsAndLiabilitiesTableTextBlock" id="Text_bc622eca11e84c0c8cebdfd099e985df" contextRef="c20200101to20201231" escape="true" continuedAt="Text_1edf0fa2617d47778479aca50af8d2a81"><ix:continuation id="Text_bf9a9759d58b4bcb96c70042a7a861e916" continuedAt="Text_bf9a9759d58b4bcb96c70042a7a861e917">
<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, 2020 and 2019 are as follows (in thousands):</div>
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<div><br /></div>
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    <td colspan="2" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DeferredTaxAssetsOperatingLossCarryforwards" id="Fact_f6113dec90244be7a15feeec0e7f99b3" contextRef="c20201231" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">83,681</ix:nonFraction></div></td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DeferredTaxAssetsOperatingLossCarryforwards" id="Fact_de531fc8054a467eb0d8ebe192e75809" contextRef="c20191231" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">20,191</ix:nonFraction></div></td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DeferredTaxAssetsTaxCreditCarryforwards" id="Fact_6e4434c808b24cdd8e98c8c527eccd87" contextRef="c20201231" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">245,746</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DeferredTaxAssetsTaxCreditCarryforwards" id="Fact_8cae73daf0c14e699722d8495d504e3f" contextRef="c20191231" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">210,455</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
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  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Deferred revenue</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DeferredTaxAssetsDeferredIncome" id="Fact_3161a0571c2d40cfa484d6df3f0587b3" contextRef="c20201231" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">124,452</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DeferredTaxAssetsDeferredIncome" id="Fact_8e7b04eb5d41408cb9a2aae8c76b704c" contextRef="c20191231" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">127,763</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#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;">Stock-based compensation</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DeferredTaxAssetsTaxDeferredExpenseCompensationAndBenefitsShareBasedCompensationCost" id="Fact_cf4d0af63f314ebebc4008a2387ff7ba" contextRef="c20201231" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">80,055</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DeferredTaxAssetsTaxDeferredExpenseCompensationAndBenefitsShareBasedCompensationCost" id="Fact_616f9b6b59aa4b9b83a42abbfc396399" contextRef="c20191231" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">65,703</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#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 colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DeferredTaxAssetsGoodwillAndIntangibleAssets" id="Fact_1eb4e0ee7798484c84a06c938cd4969a" contextRef="c20201231" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">98,443</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DeferredTaxAssetsGoodwillAndIntangibleAssets" id="Fact_5dbb3a06f1ce4e86bcf8b0b23175d4c6" contextRef="c20191231" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">77,861</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DeferredTaxAssetsOther" id="Fact_68255c3bd980428f8ac1596cf0f40278" contextRef="c20201231" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">13,402</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DeferredTaxAssetsOther" id="Fact_8fd4dba767ea4fb1ad2e077d22dd1144" contextRef="c20191231" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">12,510</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#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 colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DeferredTaxAssetsGross" id="Fact_db490d6be6234997ab204f135fae4219" contextRef="c20201231" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">645,779</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
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  <tr>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
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  <tr>
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  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;"><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" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:DeferredTaxLiabilitiesOther" id="Fact_1b5703c2c4764515a3e8ad2afeea59cf" contextRef="c20201231" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">5,808</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:DeferredTaxLiabilitiesOther" id="Fact_1b2f279a0c764ac6861cf53127c15459" contextRef="c20191231" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">3,884</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;"><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: 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 colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DeferredTaxAssetsLiabilitiesNetBeforeValuationAllowance" id="Fact_2aed2e8242ea4d2a953befcd5fd869ee" contextRef="c20201231" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">633,440</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DeferredTaxAssetsLiabilitiesNetBeforeValuationAllowance" id="Fact_079ce9450c7a4660ba7391c5cb7a50dc" contextRef="c20191231" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">502,531</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#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 colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:DeferredTaxAssetsValuationAllowance" id="Fact_972868dc5873412980ceca72fd836c11" contextRef="c20201231" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">633,440</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:DeferredTaxAssetsValuationAllowance" id="Fact_2c9b12b4481545a7ba60367cdb421919" contextRef="c20191231" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">196,974</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;"><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: 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 colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DeferredTaxAssetsLiabilitiesNet" id="Fact_57658da53796431d95347a5ae91df615" contextRef="c20201231" unitRef="U001" decimals="-3" scale="3" format="ixt:zerodash">&#8212;</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DeferredTaxAssetsLiabilitiesNet" id="Fact_b0ad9b5a1bcf4171839877e1f6c48962" contextRef="c20191231" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">305,557</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
</table>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">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;">Ionis and Akcea have filed separate U.S. federal income tax returns since Akcea&#8217;s IPO in 2017. Accordingly, we were required to assess our Ionis stand-alone and Akcea&#8217;s valuation allowances separately even though we consolidate Akcea&#8217;s financial results in our consolidated financial statements. However, as a result of the Akcea acquisition, Ionis and Akcea will file a consolidated U.S. federal income tax return beginning in the fourth quarter of 2020, and we therefore assessed our U.S. federal valuation allowance requirements on a consolidated basis as of that period. We continue to assess the state portion of our valuation allowance on a consolidated basis.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We assessed our valuation allowance requirements and recorded a valuation allowance of $<ix:nonFraction name="us-gaap:ValuationAllowancesAndReservesPeriodIncreaseDecrease" id="Fact_4c21c7d56e8b4725a58885f2600b452a" contextRef="c20201001to20201231" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">313</ix:nonFraction> million against all of Ionis&#8217; U.S. federal net deferred tax assets in the fourth quarter of 2020, due to uncertainties related to our ability to realize the tax benefits associated with these assets. This determination is based largely on Akcea rejoining the Ionis U.S. consolidated federal tax group in the fourth quarter of 2020. Due to Akcea&#8217;s historical and projected financial statement losses, and the negative impact this is expected to have on Ionis&#8217; consolidated taxable income, there is uncertainty of generating sufficient consolidated pre-tax income in future periods to realize the Ionis deferred tax benefits. It is also expected that Ionis&#8217; pre-tax income in future periods may be lower due to increased research and development expenses associated with our pipeline of wholly owned medicines. We now maintain a valuation allowance against all our consolidated U.S. federal and state net 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="c20200101to20201231" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">436</ix:nonFraction> million from December 31, 2019 to December 31, 2020. $<ix:nonFraction name="us-gaap:ValuationAllowancesAndReservesPeriodIncreaseDecrease" id="Fact_762996b749e147d68523d1e501f5e354" contextRef="c20201001to20201231" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">313</ix:nonFraction> million of the increase related to the valuation allowance established against our beginning of the year balance of Ionis&#8217; U.S. federal net deferred tax assets as discussed above, which resulted in us recognizing income tax expense during 2020. The remaining increase in our valuation allowance related to current year changes in our net 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;">At December 31, 2020, we had federal and state, primarily California, tax net operating loss carryforwards of $<ix:nonFraction name="us-gaap:OperatingLossCarryforwards" id="Fact_d9f8be4484bf4eb29dfdbd375c201523" contextRef="c20201231_IncomeTaxAuthorityNameAxis_InternalRevenueServiceIRSMember" unitRef="U001" decimals="-5" scale="6" format="ixt:numdotdecimal">243.3</ix:nonFraction> million and $<ix:nonFraction name="us-gaap:OperatingLossCarryforwards" id="Fact_ad3cae48e06445f7aefbd80a218590f4" contextRef="c20201231_IncomeTaxAuthorityNameAxis_CaliforniaFranchiseTaxBoardMember" unitRef="U001" decimals="-5" scale="6" format="ixt:numdotdecimal">346.3</ix:nonFraction> million, respectively. Our federal tax loss carryforwards are available indefinitely. Our California tax loss carryforwards will begin to expire in 2031. At December 31, 2020, we also had federal and California research and development tax credit carryforwards of $<ix:nonFraction name="us-gaap:TaxCreditCarryforwardAmount" id="Fact_895e697c597d405a96e760deb75e2c01" contextRef="c20201231_IncomeTaxAuthorityNameAxis_InternalRevenueServiceIRSMember_TaxCreditCarryforwardAxis_ResearchMember" unitRef="U001" decimals="-5" scale="6" format="ixt:numdotdecimal">210.5</ix:nonFraction> million and $<ix:nonFraction name="us-gaap:TaxCreditCarryforwardAmount" id="Fact_8191e961253a4f2faaff06f7920ca14f" contextRef="c20201231_IncomeTaxAuthorityNameAxis_CaliforniaFranchiseTaxBoardMember_TaxCreditCarryforwardAxis_ResearchMember" unitRef="U001" decimals="-5" scale="6" format="ixt:numdotdecimal">87.4</ix:nonFraction> million, respectively. Our Federal research and development tax credit carryforwards will begin to expire in 2034. Our California research and development tax credit carryforwards are available indefinitely.</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 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 (in thousands):</div>
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    <td colspan="10" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><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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  <tr>
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    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2019</div></td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Increase for prior period tax positions</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:UnrecognizedTaxBenefitsIncreasesResultingFromPriorPeriodTaxPositions" id="Fact_7d0ea3f6a325421b85ab3cbb04eb12fa" contextRef="c20180101to20181231" unitRef="U001" decimals="-3" scale="3" format="ixt:zerodash">&#8212;</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 64%; padding-bottom: 2px;"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Increase for current period tax positions</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 64%; padding-bottom: 4px; background-color: #CCEEFF;"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Ending balance of unrecognized tax benefits</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:UnrecognizedTaxBenefits" id="Fact_c2747640a25a483791181f56caf8bc45" contextRef="c20201231" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">54,163</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:UnrecognizedTaxBenefits" id="Fact_58382ea6463045ef8f7cefb3fdbf3dd7" contextRef="c20191231" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">69,784</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:UnrecognizedTaxBenefits" id="Fact_ed1574437d194d92b955e24fdec9efce" contextRef="c20181231" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">68,301</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
</table>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Included in the balance of unrecognized tax benefits at December 31, 2020 and 2019 was $<ix:nonFraction name="us-gaap:UnrecognizedTaxBenefitsThatWouldImpactEffectiveTaxRate" id="Fact_552285171ef248dfab36d0ee9948271e" contextRef="c20201231" unitRef="U001" decimals="-5" scale="6" format="ixt:numdotdecimal">6.4</ix:nonFraction> million and $<ix:nonFraction name="us-gaap:UnrecognizedTaxBenefitsThatWouldImpactEffectiveTaxRate" id="Fact_609bbfafde0b4ea9bce0bad6399c9eb6" contextRef="c20191231" unitRef="U001" decimals="-5" scale="6" format="ixt:numdotdecimal">0.4</ix:nonFraction> million respectively, that if we recognized, could impact our effective tax rate, subject to our remaining valuation allowance. <ix:nonFraction name="us-gaap:UnrecognizedTaxBenefitsThatWouldImpactEffectiveTaxRate" id="Fact_5bbe89a94abb40a2b89740ddee067f6b" contextRef="c20181231" unitRef="U001" decimals="-6" scale="6" format="ixt-sec:numwordsen">None</ix:nonFraction> of our unrecognized tax benefits recorded at December 31, 2018 would impact our effective tax rate, if we recognized them.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We do not foresee any material changes to our gross unrecognized tax benefits within the next twelve months.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We recognize interest and/or penalties related to income tax matters in income tax expense. During the year ended December 31, </span>2020<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, we recognized $</span><ix:nonFraction name="us-gaap:UnrecognizedTaxBenefitsIncomeTaxPenaltiesAndInterestExpense" id="Fact_5d817f0050924f7f82257fc7b70a23d7" contextRef="c20200101to20201231" unitRef="U001" decimals="-5" scale="6" format="ixt:numdotdecimal">0.3</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million of accrued interest and penalties related to gross unrecognized tax benefits</span>. We did <ix:nonFraction name="us-gaap:UnrecognizedTaxBenefitsIncomeTaxPenaltiesAndInterestExpense" id="Fact_3995dfebbafe49dc864f5ed1bb53c415" contextRef="c20180101to20181231" unitRef="U001" decimals="-6" scale="6" format="ixt-sec:numwordsen"><ix:nonFraction name="us-gaap:UnrecognizedTaxBenefitsIncomeTaxPenaltiesAndInterestExpense" id="Fact_2bc21e2e58634e2ca176d285cb453ec6" contextRef="c20190101to20191231" unitRef="U001" decimals="-6" scale="6" format="ixt-sec:numwordsen">no</ix:nonFraction></ix:nonFraction>t record any accrued interest and penalties for the years ended December 31, 2019 and 2018.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We are subject to taxation in the U.S. and various state and foreign jurisdictions. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Our tax years for 1999 through 2019 are subject to examination by the U.S. federal, state and foreign tax authorities.</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 do not provide for a U.S. income tax liability and foreign withholding taxes on undistributed foreign earnings of our foreign subsidiaries as we consider those earnings to be permanently reinvested. It is not practicable for us to calculate the amount of unrecognized deferred tax liabilities associated with these earnings.</div>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">6. Collaborative Arrangements and Licensing Agreements</div>
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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Strategic Partnership</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Biogen</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We have several strategic collaborations with Biogen focused on using antisense technology to advance the treatment of neurological disorders. These collaborations combine our expertise in creating antisense medicines with Biogen&#8217;s expertise in developing therapies for neurological disorders. We developed and licensed to Biogen SPINRAZA, our approved medicine to treat people with spinal muscular atrophy, or SMA. We and Biogen are currently developing <ix:nonFraction name="ions:NumberOfMedicinesBeingDeveloped" id="Fact_7af8e6ccc5734a52b212b2cb39251c85" contextRef="c20201231_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsBiogenMember" unitRef="U013" decimals="INF" scale="0" format="ixt-sec:numwordsen">eight</ix:nonFraction> investigational medicines to treat neurodegenerative diseases under these collaborations, including medicines in development to treat people with ALS, Alzheimer&#8217;s disease<sub>&#xA0;</sub>and Parkinson&#8217;s disease. In addition to these medicines, our collaborations with Biogen include a substantial research pipeline that addresses a broad range of neurological diseases. From inception through December 2020, we have received more than $<ix:nonFraction name="ions:CumulativePaymentsReceived" id="Fact_06e533557dd645a0a293de69cd61db32" contextRef="c20201231_RangeAxis_MinimumMember_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsBiogenMember" unitRef="U001" decimals="-8" scale="9" format="ixt:numdotdecimal">2.8</ix:nonFraction> billion from our Biogen collaborations.</div>
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<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Spinal Muscular Atrophy Collaborations</div>
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<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">SPINRAZA</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In January 2012, we entered into a collaboration agreement with Biogen to develop and commercialize SPINRAZA, an RNA-targeted therapy for the treatment of SMA. </span>SPINRAZA is approved in over <ix:nonFraction name="ions:NumberOfCountriesWhereDrugIsApprovedForUse" id="Fact_36f52e68092e46448c21ed2babef24c8" contextRef="c20201231_RangeAxis_MinimumMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2012WithBiogenMember" unitRef="U014" decimals="0" scale="0" format="ixt:numdotdecimal">50</ix:nonFraction> countries around the world. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">From inception through December 2020, we earned more than $</span><ix:nonFraction name="ions:CumulativeRevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_80c48219eb9e4393b8569e87d9780e38" contextRef="c20201231_RangeAxis_MinimumMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2012WithBiogenMember" unitRef="U001" decimals="-8" scale="9" format="ixt:numdotdecimal">1.3</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="c20201231_ProductOrServiceAxis_SpinrazaRoyaltiesMember_RangeAxis_MinimumMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2012WithBiogenMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">930</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million in revenue from SPINRAZA royalties and more than $</span><ix:nonFraction name="ions:CumulativeRevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_4f6bdc7d5939403c952ca9aeb8c58deb" contextRef="c20201231_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_RangeAxis_MinimumMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2012WithBiogenMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">435</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:RoyaltyPercentageReceivedOnNetSalesOfDrug" id="Fact_61c6432e61694a50bab0c763baf066d7" contextRef="c20200101to20201231_RangeAxis_MinimumMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2012WithBiogenMember" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">11</ix:nonFraction> percent<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> to </span><ix:nonFraction name="ions:RoyaltyPercentageReceivedOnNetSalesOfDrug" id="Fact_1823d09bb3e44264ad0c1a26037d2ae5" contextRef="c20200101to20201231_RangeAxis_MaximumMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2012WithBiogenMember" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">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; font-style: italic;">New antisense medicines for the treatment of SMA</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In December 2017, we entered into a collaboration agreement with Biogen to </span>identify <span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">new antisense medicines for the treatment of SMA</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. </span><span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Biogen has the option to license therapies arising out of this collaboration following the completion of preclinical studies. Upon licensing, Biogen </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">will be responsible for global development, regulatory and commercialization activities and costs for such therapies</span><span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. Under the collaboration agreement, we received a </span>$<ix:nonFraction name="ions:UpfrontPaymentReceived" id="Fact_d0f059efca0b4cb78eead790f4fa19ae" contextRef="c20171001to20171231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2017WithBiogenMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">25</ix:nonFraction> million<span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> upfront payment in the fourth quarter of 2017. We will receive development and regulatory milestone payments from Biogen if new medicines advance towards marketing approval. </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In total over the term of our collaboration, we are eligible to receive up to $</span><ix:nonFraction name="ions:MaximumAmountOfPaymentsReceivableForLicenseFeesAndMilestones" id="Fact_8fa42de141e3407c99bbfa2f29113c53" contextRef="c20201231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2017WithBiogenMember" unitRef="U001" decimals="-8" scale="9" format="ixt:numdotdecimal">1.2</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> billion in license fees, milestone payments and other payments, including up to $</span><ix:nonFraction name="ions:MaximumAmountOfPaymentsReceivableForDevelopmentMilestones" id="Fact_e38aa26f41814546bda50548960b0e5e" contextRef="c20201231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2017WithBiogenMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">80</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million for the achievement of development milestones, up to $</span><ix:nonFraction name="ions:MaximumAmountOfPaymentsReceivableForCommercializationMilestones" id="Fact_6b3fbb9794124e4184ca605383c0149b" contextRef="c20201231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2017WithBiogenMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">180</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million for the achievement of commercialization milestones and up to $</span><ix:nonFraction name="ions:MaximumAmountOfPaymentsReceivableForSalesMilestones" id="Fact_322a430335cd4f42adcade119ecaa19b" contextRef="c20201231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2017WithBiogenMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">800</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million for the achievement of sales milestones. In addition, we are eligible to receive tiered royalties </span><span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">from the mid-teens to </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">mid-</span><ix:nonFraction name="ions:RoyaltyPercentageReceivedOnNetSalesOfDrug" id="Fact_febbc9e4755e4074b3a325f2dacf1e28" contextRef="c20200101to20201231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2017WithBiogenMember" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">20</ix:nonFraction> percent<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> range </span><span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">on net sales.</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> We will achieve the next payment of up to $</span><ix:nonFraction name="ions:NextPotentialPayment" id="Fact_7d01c2380f624d1fb49986067438d3ed" contextRef="c20201231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2017WithBiogenMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">60</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">for the license of a medicine under this collaboration. </span></div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">At the commencement of this collaboration, we identified <ix:nonFraction name="ions:RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations" id="Fact_d072d638eb714ba6a26876ea2bbbb72a" contextRef="c20171231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2017WithBiogenMember" unitRef="U005" decimals="INF" scale="0" format="ixt-sec:numwordsen">one</ix:nonFraction> performance obligation, which was to perform R&amp;D services for Biogen. We determined the transaction price to be the $<ix:nonFraction name="ions:RevenueFromContractWithCustomerTransactionPrice" id="Fact_e3683f7ee88940418d4cb28dad798342" contextRef="c20171231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2017WithBiogenMember" unitRef="U001" decimals="-6" scale="6">25</ix:nonFraction> million upfront payment we received when we entered into the collaboration. We allocated the transaction price to our single performance obligation. In the fourth quarter of 2019, we completed our R&amp;D services performance obligation under this collaboration. We recognized revenue as we performed services based on our effort to satisfy our performance obligation relative to the total effort expected to satisfy our performance obligation. We completed our performance obligation earlier than we previously estimated, as a result, we recognized $<ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_4edfbf91e3db4c149d8f7c6de6cfd7f2" contextRef="c20191001to20191231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2017WithBiogenMember" unitRef="U001" decimals="-5" scale="6" format="ixt:numdotdecimal">8.3</ix:nonFraction> million of additional revenue in the fourth quarter of 2019. We do not have any remaining performance obligations under this collaboration. We will receive development and regulatory milestone payments from Biogen if Biogen advances the development candidate under this collaboration toward marketing approval.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Neurology Collaborations</div>
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<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">2018 Strategic Neurology</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In April 2018, we and Biogen entered into a strategic collaboration to develop novel antisense medicines for a broad range of neurological diseases and entered into a 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="c20200101to20201231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember" format="ixt-sec:duryear">10</ix:nonNumeric><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> years. We are responsible for the identification of antisense drug candidates based on selected medicines</span>. Biogen is responsible for conducting IND-enabling toxicology studies for the selected medicine. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Biogen will have the option to license the selected medicine </span>after it completes the IND-enabling toxicology study. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">If Biogen exercises its option to license a medicine, it will assume global development, regulatory and commercialization responsibilities and costs for that medicine.</span></div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In the second quarter of 2018, we received </span>$<ix:nonFraction name="ions:UpfrontPaymentReceivedIncludingPurchaseOfStock" id="Fact_976237d61b074e5e9b91af22b9df351f" contextRef="c20180401to20180630_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember" unitRef="U001" decimals="-9" scale="9" format="ixt:numdotdecimal">1</ix:nonFraction> billion from Biogen, comprised of $<ix:nonFraction name="us-gaap:ProceedsFromIssuanceOfCommonStock" id="Fact_271dd8aced544c41be19b5a818ba4058" contextRef="c20180401to20180630_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">625</ix:nonFraction> million to purchase our stock at an approximately <ix:nonFraction name="ions:PercentageCashPremiumPaidOnSharesPurchased" id="Fact_c96d0cb6c7e643c7b9c75b57384aa601" contextRef="c20180401to20180630_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">25</ix:nonFraction> percent cash premium and $<ix:nonFraction name="ions:UpfrontPaymentReceived" id="Fact_755b026d1fee41558d1dc2c5b62ee556" contextRef="c20180401to20180630_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">375</ix:nonFraction> million in an upfront payment. <span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We are eligible to receive up to $</span><ix:nonFraction name="ions:MaximumAmountOfPaymentsReceivablePerDrugForSubstantiveMilestonePayments" id="Fact_62648637171d42169a691df96b84fa12" contextRef="c20201231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">270</ix:nonFraction><span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million in milestone payments for each medicine that achieves marketing approval. </span>In addition, we are eligible to receive tiered royalties <span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">up to the </span><ix:nonFraction name="ions:RoyaltyPercentageReceivedOnNetSalesOfDrug" id="Fact_210a08ece63647968230838a5127deb6" contextRef="c20200101to20201231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">20</ix:nonFraction> percent range <span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">on net sales.</span>&#xA0;<span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">W</span>e are advancing <ix:nonFraction name="ions:NumberOfProgramsBeingAdvanced" id="Fact_bcc6f527b7724a709204e78caa6a12c2" contextRef="c20201231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember" unitRef="U015" decimals="INF" scale="0" format="ixt-sec:numwordsen">eight</ix:nonFraction> programs under this collaboration and from inception through December 2020, we have received $<ix:nonFraction name="ions:CumulativePaymentsReceived" id="Fact_da56d1dc03c24e66a27cff951a361cbb" contextRef="c20201231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember" unitRef="U001" decimals="-7" scale="9" format="ixt:numdotdecimal">1.05</ix:nonFraction> billion in payments under this collaboration. We will achieve the next payment of $<ix:nonFraction name="ions:NextPotentialPayment" id="Fact_2ccf74adb28c46398e26d42924be60cb" contextRef="c20201231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember" unitRef="U001" decimals="-5" scale="6" format="ixt:numdotdecimal">7.5</ix:nonFraction> million if we advance a program<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">under this collaboration. </span></div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">At the commencement of this collaboration, </span>we identified <ix:nonFraction name="ions:RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations" id="Fact_5e47f934a68347d89f25d91842517b61" contextRef="c20180430_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember" unitRef="U005" 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_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">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_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">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_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">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 2020, we have included $<ix:nonFraction name="ions:CumulativePaymentsIncludedInTransactionPriceForPerformanceObligation" id="Fact_20ba18c7432f48b692b7d780c2e643aa" contextRef="c20201231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">608</ix:nonFraction> million <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">in payments in the transaction price for our R&amp;D services performance obligation under this collaboration, including $</span><ix:nonFraction name="ions:MilestonePaymentsAchievedAndIncludedInTransactionPriceForPerformanceObligation" id="Fact_3f7c210dad714493961c539d0e6cfc20" contextRef="c20200101to20201231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">11</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million of milestone payments we achieved in 2020 and $</span><ix:nonFraction name="ions:MilestonePaymentsAchievedAndIncludedInTransactionPriceForPerformanceObligation" id="Fact_c3f14a3ed4c14ef2b91a6574e6cdd6e4" contextRef="c20190101to20191231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">30</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million of milestone payments we achieved in 2019. These milestone payments did not create new performance obligations because they are part of our original R&amp;D services performance obligation. Therefore, we included these amounts in our transaction price for our R&amp;D services performance obligation in the period we achieved the milestone payment. We are recognizing revenue for our R&amp;D services performance obligation as we perform services based on our effort to satisfy our performance obligation relative to our total effort expected to satisfy our performance obligation. We currently estimate we will satisfy our performance obligation at the end of the contractual term in June 2028.</span></div>
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<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">2013 Strategic Neurology</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In September 2013, we and Biogen entered into a long-term strategic relationship focused on applying antisense technology to advance the treatment of neurodegenerative diseases. As part of the collaboration, Biogen gained exclusive rights to the use of our antisense technology to develop therapies for neurological diseases and has the option to license medicines resulting from this collaboration. We will usually be responsible for drug discovery and early development of antisense medicines and Biogen will have the option to license antisense medicines after Phase 2 proof-of-concept. In October 2016, we expanded our collaboration to include additional research activities we will perform. If Biogen exercises its option to license a medicine, it will assume global development, regulatory and commercialization responsibilities and costs for that medicine. We are currently advancing <ix:nonFraction name="ions:NumberOfMedicinesCurrentlyBeingAdvanced" id="Fact_eb09908f5c9a48cc93d43f56069f13ca" contextRef="c20201231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember" unitRef="U013" decimals="INF" scale="0" format="ixt-sec:numwordsen">six</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="c20201231_ProductOrServiceAxis_MedicinesForAmyotrophicLateralSclerosisMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember" unitRef="U013" decimals="INF" scale="0" format="ixt-sec:numwordsen">three</ix:nonFraction> medicines for ALS (tofersen, IONIS-C9<sub>Rx</sub> and ION541), <span style="-sec-ix-hidden:Fact_7b05dc571fcb46f8bbbe0db51a44d460">a</span> medicine for multiple system atrophy (ION464) and <span style="-sec-ix-hidden:Fact_33617a5e2de04e8688f1a06dd038ea29">a</span> medicine for an undisclosed target. In the fourth quarter of 2018, Biogen exercised its option to license our most advanced ALS medicine, tofersen, our medicine in Phase 3 development for SOD1 ALS. As a result, Biogen is now responsible for global development, regulatory and commercialization activities and costs for tofersen.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Under the terms of the agreement, we received an upfront payment of $<ix:nonFraction name="ions:UpfrontPaymentReceived" id="Fact_df6e4e7a86a541f1926d3e828e7efea5" contextRef="c20130901to20130930_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">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. For each antisense molecule that is chosen for drug discovery and development under this collaboration, we are eligible to receive up to approximately $<ix:nonFraction name="ions:MaximumAmountOfPaymentsReceivablePerDrugOrProgramForLicenseFeesAndSubstantiveMilestonePayments" id="Fact_e29891c91d1a456e9cb73201cb58d5f4" contextRef="c20201231_ProductOrServiceAxis_AntisenseMoleculeMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">260</ix:nonFraction> million in a license fee and milestone payments per program. The $<ix:nonFraction name="ions:MaximumAmountOfPaymentsReceivablePerDrugOrProgramForLicenseFeesAndSubstantiveMilestonePayments" id="Fact_0dfbd8128b624f969b95f7ef71d4d44f" contextRef="c20201231_ProductOrServiceAxis_AntisenseMoleculeMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">260</ix:nonFraction> million per program consists of approximately $<ix:nonFraction name="ions:MaximumAmountOfPaymentsReceivablePerDrugOrProgramForDevelopmentMilestones" id="Fact_245f4587f74e4be8b4a2a97ac77ea0f6" contextRef="c20201231_ProductOrServiceAxis_AntisenseMoleculeMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">60</ix:nonFraction> million in development milestones, including amounts related to the cost of clinical trials, and up to $<ix:nonFraction name="ions:MaximumAmountOfPaymentsReceivablePerDrugOrProgramForRegulatoryMilestones" id="Fact_c1d1f25511534235862a7aa4449afd2d" contextRef="c20201231_ProductOrServiceAxis_AntisenseMoleculeMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">130</ix:nonFraction> million in milestone payments if Biogen achieves pre-specified regulatory milestones. In addition, we are eligible to receive tiered royalties up to the mid-teens on net sales from any antisense medicines developed under this collaboration. From inception through December 2020, we have received over $<ix:nonFraction name="ions:CumulativePaymentsReceived" id="Fact_43252364b31243cf9fe665618b7d0d4d" contextRef="c20201231_RangeAxis_MinimumMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">270</ix:nonFraction> million in upfront fees, milestone payments and other payments under this collaboration. We will achieve the next payment of up to $<ix:nonFraction name="ions:NextPotentialPayment" id="Fact_531e5e06da924c38a4eddf832276baff" contextRef="c20201231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">10</ix:nonFraction> million if we advance a program 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_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember" unitRef="U005" 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_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">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>In the third quarter of 2019, we updated our estimate of the total effort we expect to expend to satisfy our performance obligation. As a result, we recorded a cumulative catch up adjustment of $<ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_b62f5dd4cf444635b5e8c1a45181319c" contextRef="c20190701to20190930_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember" unitRef="U001" decimals="-5" scale="6" sign="-" format="ixt:numdotdecimal">16.5</ix:nonFraction> million to decrease revenue in the third quarter of 2019. During 2020, we completed our remaining<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> research and development services and recognized the remaining revenue related to this performance obligation. </span>From inception through the completion of our R&amp;D services performance obligation in <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">2020</span>, we included $<ix:nonFraction name="ions:CumulativePaymentsIncludedInTransactionPriceForPerformanceObligation" id="Fact_8e6bac473c9a4873a7bb0e87fa0b76df" contextRef="c20201231_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">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;">Under this collaboration, we have also generated additional payments that we concluded were not part of our R&amp;D services performance obligation. We recognized each of these payments in full in the respective quarter we generated the payment because we did not have any performance obligations for the respective payment. The following are the payments we earned:</div>
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    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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 third quarter of 2018, we earned a $<ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_63dec559cce845c6b0ef765a3708692b" contextRef="c20180701to20180930_ProductOrServiceAxis_IonisC9Member_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">10</ix:nonFraction> million milestone payment when Biogen initiated a Phase 1 study of IONIS-C9<sub>Rx</sub>.</div></td>
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    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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 fourth quarter of 2018, we earned a $<ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_81e42ca6272446b1b4943add62dab9b1" contextRef="c20181001to20181231_ProductOrServiceAxis_LicensingAndOtherRoyaltiesMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">35</ix:nonFraction> million license fee when Biogen licensed tofersen from us because Biogen had full use of the licenses without any continuing involvement from us.</div></td>
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    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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 fourth quarter of 2018, we earned <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">a $</span><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_006f69b7a4444911a0f6769b45a080a9" contextRef="c20181001to20181231_ProductOrServiceAxis_TofersenMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">5</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million milestone when Biogen initiated a Proof-of-Concept study for tofersen.</span></div></td>
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    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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 third quarter of 2019, we earned an $<ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_ccce677ba0b14a499d2ffb36507cc46d" contextRef="c20190701to20190930_ProductOrServiceAxis_Ion859Member_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">8</ix:nonFraction> million milestone payment when Biogen initiated a Phase 1/2 study of ION859 <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">for the treatment of people with Parkinson&#8217;s disease </span>under this collaboration.</div></td>
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    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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 fourth quarter of 2019, we earned a $<ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_c73bcf5effca436fa5cef751e9a6c8ca" contextRef="c20191001to20191231_ProductOrServiceAxis_IonisC9Member_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">10</ix:nonFraction> million milestone payment when Biogen advanced IONIS-C9<sub>Rx</sub>.</div></td>
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    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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 third quarter of 2020, we earned $<ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_dbf083656e294da0b9665f432fcfc0dc" contextRef="c20200701to20200930_ProductOrServiceAxis_Ion464Member_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">18</ix:nonFraction> million in milestone payments when Biogen initiated<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> a Phase 1/2 trial for ION464, an investigational medicine in development targeting alpha-synuclein to treat patients with multiple system atrophy.</span></div></td>
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    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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 third quarter of 2020, w<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">e earned a $</span><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_cdb7253065694d2ebaa75bdc5cef9a59" contextRef="c20200701to20200930_ProductOrServiceAxis_Ion541Member_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">10</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million milestone payment when Biogen initiated a Phase 1/2 trial for ION541, an investigational medicine in development targeting ataxin 2 to treat patients with ALS.</span></div></td>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">2012 Neurology</div>
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<div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In December 2012, we and Biogen entered into a collaboration agreement to develop and commercialize novel antisense medicines to treat neurodegenerative diseases. We are responsible for the development of each of the medicines through the completion of the initial Phase 2 clinical study for such medicine. Biogen has the option to license a medicine from each of the programs through the completion of the first Phase 2 study for each program. Under this collaboration, we are currently advancing IONIS-MAPT<sub>Rx</sub> for Alzheimer&#8217;s disease and ION582 for Angelman syndrome. If Biogen exercises its option to license a medicine, it will assume global development, regulatory and commercialization responsibilities and costs for that medicine. In the fourth quarter of 2019, Biogen exercised its option to license IONIS-MAPT<sub>Rx</sub>. We are responsible for completing the Phase 1/2 in study patients with mild AD and a <ix:nonNumeric name="ions:TermOfExtensionStudy" id="Fact_c9487a6f142a4d15bf3c0d28e9000ec3" contextRef="c20200101to20201231_ProductOrServiceAxis_IonisMaptMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember" format="ixt-sec:durwordsen">one-year</ix:nonNumeric> long-term extension study. Biogen will have 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: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Under the terms of the agreement, we received an upfront payment of $</span><ix:nonFraction name="ions:UpfrontPaymentReceived" id="Fact_96e0bfc66c13486cb77a67ff0bc02893" contextRef="c20121201to20121231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">30</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million. Over the term of the collaboration, we are eligible to receive up to $</span><ix:nonFraction name="ions:MaximumAmountOfPaymentsReceivablePerDrugOrProgramForLicenseFeesAndSubstantiveMilestonePayments" id="Fact_ca3ece52a6764f27b53aa658420e1e3c" contextRef="c20201231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">210</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million in a license fee and milestone payments per program, plus a mark-up on the cost estimate of the Phase 1 and 2 studies. The $</span><ix:nonFraction name="ions:MaximumAmountOfPaymentsReceivablePerDrugOrProgramForLicenseFeesAndSubstantiveMilestonePayments" id="Fact_0bbe193efceb411386581d3674a65290" contextRef="c20201231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">210</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million per program consists of up to $</span><ix:nonFraction name="ions:MaximumAmountOfPaymentsReceivablePerDrugOrProgramForDevelopmentMilestones" id="Fact_75f24e61b9f94c949ecc39419626d788" contextRef="c20201231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">10</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million in development milestone payments, plus a mark-up on the cost estimate of the Phase 1 and 2 studies and up to $</span><ix:nonFraction name="ions:MaximumAmountOfPaymentsReceivablePerDrugOrProgramForRegulatoryMilestones" id="Fact_12ca19bdf13e48ffb87ff55a87528661" contextRef="c20201231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">130</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million in milestone payments if Biogen achieves pre-specified regulatory milestones. 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:NumberOfProgramsUnderWhichDrugsAreToBeDevelopedAndCommercialized" id="Fact_a9dc5fc90fff488ab419c13f5bd3df17" contextRef="c20121231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember" unitRef="U015" decimals="INF" scale="0" format="ixt-sec:numwordsen">three</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> programs. From inception through December 2020, we have received $</span><ix:nonFraction name="ions:CumulativePaymentsReceived" id="Fact_7a4c67230f974ba9bfd049a2c63e615a" contextRef="c20201231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">154</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_abf873dddd774737b5bca23e66c6105d" contextRef="c20200101to20201231_ProductOrServiceAxis_IonisMaptMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember" unitRef="U001" decimals="-5" scale="6" format="ixt:numdotdecimal">19.5</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million we received from Biogen for achieving milestones for advancing IONIS-MAPT</span><sub>Rx </sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">during 2020. We will achieve the next payment of $</span><ix:nonFraction name="ions:NextPotentialPayment" id="Fact_7bc80b0e8adf47ca8dd64914ace6d170" contextRef="c20201231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">25</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#xA0;</span>million if we continue to advance 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;">Under our collaboration, we determined we had a performance obligation to perform R&amp;D services. We allocated $<ix:nonFraction name="ions:CumulativePaymentsIncludedInTransactionPriceForPerformanceObligation" id="Fact_1381ecc294394ea081d42cec69196f2b" contextRef="c20201231_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">40</ix:nonFraction> million in total payments to the transaction price for our R&amp;D services performance obligation. In the third quarter of 2019, we completed our R&amp;D services performance obligation when we designated a development candidate and Biogen accepted the development candidate. Biogen&#8217;s decision to accept the development candidate was not within our control. We were recognizing revenue as we performed services based on our effort to satisfy our performance obligation relative to the total effort expected to satisfy our performance obligation. Because Biogen accepted the development candidate earlier than when we were previously estimating, we recognized $<ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_6edc31f3d40d48f3944b9cbb4ebd25f4" contextRef="c20190701to20190930_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember" unitRef="U001" decimals="-5" scale="6" format="ixt:numdotdecimal">6.3</ix:nonFraction> million of accelerated revenue in the third quarter of 2019.</div>
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<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">F-<span>41</span></div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">When we commenced development for IONIS-MAPT<sub>Rx</sub> we identified our development work as a separate performance obligation. We are recognizing our IONIS-MAPT<sub>Rx</sub> development performance obligation based on the percentage of completion. From inception through December 2020, we have included $<ix:nonFraction name="ions:CumulativePaymentsIncludedInTransactionPriceForPerformanceObligation" id="Fact_65c25865c5cb46d88f766f99f72dcb07" contextRef="c20201231_ProductOrServiceAxis_IonisMaptMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">57</ix:nonFraction> million in the transaction price for our IONIS-MAPT<sub>Rx</sub> development performance obligation. We currently estimate we will satisfy our performance obligation in 2022. Our total transaction price for our IONIS-MAPT<sub>Rx </sub>development performance obligation includes the following payments we achieved in 2019 and 2020 related to our development work:</div>
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<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="z71d69a9d13b14163a88f7ddf594f4ca2">
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    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In the second quarter of 2019, we achieved a $<ix:nonFraction name="ions:MilestonePaymentsAchievedAndIncludedInTransactionPriceForPerformanceObligation" id="Fact_3c32ab7ce0d44bd481aa51cfd2e1370a" contextRef="c20190401to20190630_ProductOrServiceAxis_IonisMaptMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember" unitRef="U001" decimals="-5" scale="6" format="ixt:numdotdecimal">7.5</ix:nonFraction> million milestone payment from Biogen when we advanced IONIS-MAPT<sub>Rx</sub>.</div></td>
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    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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 fourth quarter of 2019, we achieved a $<ix:nonFraction name="ions:MilestonePaymentsAchievedAndIncludedInTransactionPriceForPerformanceObligation" id="Fact_2b75fa090cd64885ab1ec1aa299e2584" contextRef="c20191001to20191231_ProductOrServiceAxis_IonisMaptMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">12</ix:nonFraction> million milestone payment from Biogen when we entered into an agreement to conduct a long-term extension study for IONIS-MAPT<sub>Rx</sub>.</div></td>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In the fourth quarter of 2019, we identified another performance obligation upon Biogen&#8217;s license of IONIS-MAPT<sub>Rx</sub> because the license we granted to Biogen is distinct from our other performance obligations. We recognized the $<ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_15e8499c99b84633ab63c1a97bb470f3" contextRef="c20191001to20191231_ProductOrServiceAxis_IonisMaptMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">45</ix:nonFraction> million license fee for IONIS-MAPT<sub>Rx</sub> as revenue at that time because Biogen had full use of the license without any continuing involvement from us. Additionally, we did not have any further performance obligations related to the license after we delivered it to Biogen.</div>
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<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In the fourth quarter of 2019, we <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">earned a $</span><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_68b4f122e6a446cf9ecf4f8f9556c677" contextRef="c20191001to20191231_ProductOrServiceAxis_Ion582Member_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">10</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million milestone payment when Biogen advanced ION582. We recognized this milestone payment in full in the fourth quarter of 2019 because we did not have any performance obligations related to this milestone payment.</span></div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">During the years ended December 31, 2020, 2019 and 2018, we earned the following revenue from our relationship with Biogen (in millions, except percentage amounts):</div>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br /></div>
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<div style="text-align: 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 sheet at <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">December 31, </span>2020<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> and </span>2019<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="c20201231_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsBiogenMember" unitRef="U001" decimals="-5" scale="6" format="ixt:numdotdecimal">465.8</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="c20191231_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsBiogenMember" unitRef="U001" decimals="-5" scale="6" format="ixt:numdotdecimal">525.8</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: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Research, Development and Commercialization Partners</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 <ix:nonFraction name="ions:NumberOfCollaborationAgreements" id="Fact_9c8361df6fea4b218f0efeaa69ad50e4" contextRef="c20201231_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsAstrazenecaMember" unitRef="U006" decimals="INF" scale="0" format="ixt-sec:numwordsen">two</ix:nonFraction> collaborations with AstraZeneca, <ix:nonFraction name="ions:NumberOfCollaborationAgreements" id="Fact_046b1e0f12174cf99654ee0d525312c4" contextRef="c20201231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJuly2015WithAstrazenecaMember" unitRef="U006" decimals="INF" scale="0" format="ixt-sec:numwordsen">one</ix:nonFraction> focused on the treatment of cardiovascular, renal and metabolic diseases and a <span style="-sec-ix-hidden:Fact_bba64ca284c648c3b9f851d0da94ba68">second</span> focused on the treatment of oncology diseases. We and AstraZeneca are currently developing several investigational medicines under these collaborations, including medicines in development to treat people with cardiovascular disease, a genetically associated form of kidney disease, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">nonalcoholic steatohepatitis, or NASH, and cancer</span>. From inception through December 2020, we have received more than $<ix:nonFraction name="ions:CumulativePaymentsReceived" id="Fact_c392bb35c69a431a8ccd8f4e7ecf96f0" contextRef="c20201231_RangeAxis_MinimumMember_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsAstrazenecaMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">380</ix:nonFraction> million from our AstraZeneca collaborations.</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;">&#160;Cardiovascular, Renal and Metabolic Diseases 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 July 2015, we and AstraZeneca formed a collaboration to discover and develop antisense therapies for treating cardiovascular, renal and metabolic diseases. Under our collaboration, AstraZeneca has licensed <ix:nonFraction name="ions:NumberOfLicensedMedicines" id="Fact_b682e7d57d3a45c18d753ca8d347beeb" contextRef="c20201231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJuly2015WithAstrazenecaMember" unitRef="U013" decimals="INF" scale="0" format="ixt-sec:numwordsen">four</ix:nonFraction> medicines from us:</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;">ION449 (formerly IONIS-AZ4-2.5-L<sub>Rx</sub>), an investigational medicine we designed to reduce the liver production of PCSK9 and lower the plasma level of LDL-C and thus reduce the risk of cardiovascular disease;</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;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">ION532, an investigational medicine we designed to reduce the production of APOL1 for the </span>treatment of APOL1-associated chronic kidney disease;</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;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">ION839, an investigational medicine we designed to </span>inhibit the production of PNPLA3 protein, a major genetic determinant of NASH progression<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">; and</span></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;">ION455, an investigational medicine we designed as a potential treatment for NASH.</div></td>
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<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">F-<span>42</span></div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">AstraZeneca is responsible for global development, regulatory and commercialization activities and costs for each of the medicines it has licensed and any medicines AstraZeneca licenses in the future.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Under the terms of the agreement, we received a $<ix:nonFraction name="ions:UpfrontPaymentReceived" id="Fact_afe0e303f52c47de8fef2665adbb52f3" contextRef="c20150701to20150731_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJuly2015WithAstrazenecaMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">65</ix:nonFraction> million upfront payment. We are eligible to receive license fees and milestone payments of up to more than $<ix:nonFraction name="ions:MinimumAmountOfPaymentsReceivableForLicenseFeesAndSubstantiveMilestones" id="Fact_681cbdadca67472d9b022f4711037c7f" contextRef="c20201231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJuly2015WithAstrazenecaMember" unitRef="U001" decimals="-8" scale="9" format="ixt:numdotdecimal">5.5</ix:nonFraction> billion as medicines under this collaboration advance, including up to $<ix:nonFraction name="ions:MaximumAmountOfPaymentsReceivableForDevelopmentMilestones" id="Fact_8bf17f1115c642a893b55340a0970cea" contextRef="c20201231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJuly2015WithAstrazenecaMember" unitRef="U001" decimals="-8" scale="9" format="ixt:numdotdecimal">1.1</ix:nonFraction> billion for the achievement of development milestones, up to $<ix:nonFraction name="ions:MaximumAmountOfPaymentsReceivableForRegulatoryMilestones" id="Fact_efb4704088a04a6e826d67ea5c2f326d" contextRef="c20201231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJuly2015WithAstrazenecaMember" unitRef="U001" decimals="-8" scale="9" format="ixt:numdotdecimal">2.9</ix:nonFraction> billion for regulatory milestones and up to $<ix:nonFraction name="ions:MaximumAmountOfPaymentsReceivableForCommercializationMilestones" id="Fact_dec66cb0ecac4e4691af3624c8c46a68" contextRef="c20201231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJuly2015WithAstrazenecaMember" unitRef="U001" decimals="-8" scale="9" format="ixt:numdotdecimal">1.5</ix:nonFraction> billion for commercial milestones. In addition, we are eligible to receive tiered royalties up to the low teens on net sales from any product that AstraZeneca successfully commercializes under this collaboration agreement. We will achieve the next payment of up to $<ix:nonFraction name="ions:NextPotentialPayment" id="Fact_2b949e7c63b941a3955f5c01227834d5" contextRef="c20201231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJuly2015WithAstrazenecaMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">30</ix:nonFraction> million under this collaboration if AstraZeneca advances a medicine under this collaboration<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">.</span> From inception through December 2020, we have received over $<ix:nonFraction name="ions:CumulativePaymentsReceived" id="Fact_b46d3be360f94ea788b2b83ce6c73f6f" contextRef="c20201231_RangeAxis_MinimumMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJuly2015WithAstrazenecaMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">235</ix:nonFraction> million in upfront fees, license fees, milestone payments, and other payments under this collaboration, including $<ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_f5235f06908f4bce87d2480d78228cf9" contextRef="c20200101to20201231_ProductOrServiceAxis_Ion455Member_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJuly2015WithAstrazenecaMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">30</ix:nonFraction> million we earned in 2020 when AstraZeneca licensed ION455 and $<ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_ab6e5b3862c849369666277295e2db27" contextRef="c20200101to20201231_ProductOrServiceAxis_Ion532AndIon449Member_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJuly2015WithAstrazenecaMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">30</ix:nonFraction> million in milestone payments we earned in 2020 when AstraZeneca advanced ION532 and ION449 in development.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">At the commencement of this collaboration, we identified <ix:nonFraction name="ions:RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations" id="Fact_12852f4c3cee4a69b4f4fee5d29498e6" contextRef="c20150731_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJuly2015WithAstrazenecaMember" unitRef="U005" 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_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJuly2015WithAstrazenecaMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">65</ix:nonFraction> million upfront payment we received and we allocated it to our single performance obligation. We are recognizing revenue for our R&amp;D services performance obligation as we perform services based on our effort to satisfy 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;"> currently estimate we will satisfy this performance obligation in</span> the third quarter of 2021. 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. From inception through December<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> 2020</span>, we have included $<ix:nonFraction name="ions:CumulativePaymentsIncludedInTransactionPriceForPerformanceObligation" id="Fact_ec77e25e50654249ba1ef8f5f9e4a1d1" contextRef="c20201231_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJuly2015WithAstrazenecaMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">90</ix:nonFraction> million in payments in the transaction price for our R&amp;D services performance obligation.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Under this collaboration, we have also generated additional payments that we concluded were not part of our R&amp;D services performance obligation. We recognized each of these payments in full in the respective quarter we generated the payment because the payments were distinct and we did not have any performance obligations for the respective payment. The following are the payments we have earned:</div>
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    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In the first quarter of 2018, we earned </span><ix:nonFraction name="ions:NumberOfLicenseFeesEarned" id="Fact_cae7641b707f452289941fceefd520c1" contextRef="c20180101to20180331_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJuly2015WithAstrazenecaMember" unitRef="U016" decimals="INF" scale="0" format="ixt-sec:numwordsen">two</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#xA0;</span>$<ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_e5a7b501073741939fc54a02add83b3a" contextRef="c20180101to20180331_ProductOrServiceAxis_Ion839Member_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJuly2015WithAstrazenecaMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_e85c6c9e30914bd0a8087a5b903ad7e9" contextRef="c20180101to20180331_ProductOrServiceAxis_Ion532Member_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJuly2015WithAstrazenecaMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">30</ix:nonFraction></ix:nonFraction> million license fees when AstraZeneca licensed ION532 and ION839 because AstraZeneca had full use of the licenses without any continuing involvement from us.</div></td>
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    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In the third quarter of 2018, we earned a $<ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_b354e861c2bd46999901a4505b256e38" contextRef="c20180701to20180930_ProductOrServiceAxis_Ion449Member_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJuly2015WithAstrazenecaMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">10</ix:nonFraction> million milestone payment when AstraZeneca initiated a Phase 1 study of ION449.</div></td>
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    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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 fourth quarter of 2019, we earned a $<ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_344416977fa842688cb3eb2ccbfc49f5" contextRef="c20191001to20191231_ProductOrServiceAxis_Ion839Member_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJuly2015WithAstrazenecaMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">10</ix:nonFraction> million milestone payment when AstraZeneca initiated a Phase 1 study of ION839.</div></td>
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    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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 first quarter of 2020, we earned a $<ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_4f92e5203a224dacbb79beb8c894a627" contextRef="c20200101to20200331_ProductOrServiceAxis_Ion532Member_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJuly2015WithAstrazenecaMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">10</ix:nonFraction> million milestone payment when AstraZeneca advanced ION532.</div></td>
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    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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 fourth quarter of 2020, we earned a $<ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_9d9bb9d402b14a0e93ae50b1ab26fa0f" contextRef="c20201001to20201231_ProductOrServiceAxis_Ion449Member_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJuly2015WithAstrazenecaMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">20</ix:nonFraction> million milestone payment when AstraZeneca advanced ION449.</div></td>
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    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In the fourth quarter of 2020, we earned a </span>$<ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_3d84e1afe28b4945a451c7432d891461" contextRef="c20201001to20201231_ProductOrServiceAxis_Ion455Member_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJuly2015WithAstrazenecaMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">30</ix:nonFraction> million license fee when AstraZeneca licensed ION455 because AstraZeneca had full use of the license without any continuing involvement from us.</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;">Oncology Collaboration</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In December 2012, we entered into a collaboration agreement with AstraZeneca to discover and develop antisense medicines to treat cancer. We and AstraZeneca also established an oncology research program. AstraZeneca has the option to license medicines resulting from the program, and if AstraZeneca exercises its option to license a medicine, it will be responsible for global development, regulatory and commercialization activities and costs for such medicine. In 2020, AstraZeneca licensed ION736, an investigational medicine in development targeting FOXP3 for the treatment of cancer.</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 this agreement, we received $</span><ix:nonFraction name="ions:UpfrontPaymentReceived" id="Fact_2cd1bc1d00e14c1d84b80c4ee6e222db" contextRef="c20121201to20121231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithAstrazenecaMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">31</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million in upfront payments. We are eligible to receive milestone payments and license fees up to more than $</span><ix:nonFraction name="ions:MinimumAmountOfPaymentsReceivableForLicenseFeesAndSubstantiveMilestones" id="Fact_4f1f67e17be24802be2180cf687dd301" contextRef="c20201231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithAstrazenecaMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">265</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million under this collaboration, including up to $</span><ix:nonFraction name="ions:MaximumAmountOfPaymentsReceivableForDevelopmentMilestones" id="Fact_484e8f6f1dd242f5996c00b362124558" contextRef="c20201231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithAstrazenecaMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">107</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million for the achievement of development milestones and up to $</span><ix:nonFraction name="ions:MaximumAmountOfPaymentsReceivableForRegulatoryMilestones" id="Fact_20c0e0a8259e44148a7d32d9c9881c8c" contextRef="c20201231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithAstrazenecaMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">105</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million for the achievement of regulatory milestones. 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 2020, we have received over $</span><ix:nonFraction name="ions:CumulativePaymentsReceived" id="Fact_ec695803788a443b8addc8655e99aaa7" contextRef="c20201231_RangeAxis_MinimumMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithAstrazenecaMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">140</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million in upfront fees, milestone payments, and other payments under this oncology collaboration, including $</span><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_af2cf5e17c1149358b7f65f52652d579" contextRef="c20200101to20201231_ProductOrServiceAxis_Ion736Member_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithAstrazenecaMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">13</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million we earned when AstraZeneca licensed</span> ION736 in 2020. We <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">will achieve the next payment of $</span><ix:nonFraction name="ions:NextPotentialPayment" id="Fact_9d85706b0d4c4c5dbc82e0700a25253c" contextRef="c20201231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithAstrazenecaMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">12</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">if AstraZeneca advances ION736 in development.</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 completed all of the performance obligations we identified under this collaboration in the first quarter of 2018.</div>
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<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">F-<span>43</span></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 other performance obligations discussed above. We recognized each of these payments in full in the respective quarter we generated the payment because the payments were distinct and we did not have any performance obligations for the respective payment. The following are the payments we have earned:</div>
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<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="z2bdcc0a9c35d483d9c8c7f4a41bc0cfb">
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    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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 fourth quarter of 2018, we earned a $<ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_2c2750daedb84d4285c346d6c1676448" contextRef="c20181001to20181231_ProductOrServiceAxis_DanvatirsenMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithAstrazenecaMember" unitRef="U001" decimals="-5" scale="6" format="ixt:numdotdecimal">17.5</ix:nonFraction> million milestone payment and a $<ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_c12e1cf9eef04dedbdefabddee95ccee" contextRef="c20181001to20181231_ProductOrServiceAxis_Ion736Member_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithAstrazenecaMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">10</ix:nonFraction> million milestone payment when AstraZeneca advanced <ix:nonFraction name="ions:NumberOfProgramsAdvanced" id="Fact_869d672b0b0d4547ab0774a9a808f2d8" contextRef="c20181001to20181231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithAstrazenecaMember" unitRef="U015" decimals="INF" scale="0" format="ixt-sec:numwordsen">two</ix:nonFraction> programs under our collaboration.</div></td>
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<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="z79487d3e861444efb73a94ea6625d8c5">
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    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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;">In the second quarter of 2020, we earned a $</span><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_1540196400da494babcf5e38f511ee10" contextRef="c20200401to20200630_ProductOrServiceAxis_Ion736Member_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithAstrazenecaMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">13</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million license fee when AstraZeneca licensed ION736</span> because AstraZeneca had full use of the license without any continuing involvement from us.</div></td>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">During the years ended December 31, 2020, 2019 and 2018, we earned the following revenue from our relationship with AstraZeneca (in millions, except percentage amounts):</div>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2020</div></td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2019</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2018</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#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;">Our </span>consolidated balance sheet at <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">December 31, </span>2020<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> and </span>2019<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_c0d98582c04c40f885040e43e3e95697" contextRef="c20201231_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsAstrazenecaMember" unitRef="U001" decimals="-5" scale="6" format="ixt:numdotdecimal">10.0</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_29e93280d0e245d79babbeeaf1bba43f" contextRef="c20191231_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsAstrazenecaMember" unitRef="U001" decimals="-5" scale="6" format="ixt:numdotdecimal">25.0</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million, respectively, related to our relationship with AstraZeneca.</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;">Bayer</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In May 2015, we entered into an exclusive license agreement with Bayer to develop and commercialize IONIS-FXI<sub>Rx</sub> for the prevention of thrombosis. We were responsible for completing a Phase 2 study of IONIS-FXI<sub>Rx</sub> in people with end-stage renal disease on hemodialysis. Under the terms of the agreement, we received a $<ix:nonFraction name="ions:UpfrontPaymentReceived" id="Fact_1ecc831150824141bd76a92d58b3f591" contextRef="c20150401to20150630_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMay2015WithBayerMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">100</ix:nonFraction> million upfront payment in the second quarter of 2015. In February 2017, we amended our agreement with Bayer to advance IONIS-FXI<sub>Rx</sub> and to initiate development of IONIS-FXI-L<sub>Rx</sub>, which Bayer licensed. In conjunction with the decision to advance these programs, we received a $<ix:nonFraction name="ions:PaymentReceivedForAdvancingPrograms" id="Fact_27a5975c2c5d4ed98e446e999c953f35" contextRef="c20170201to20170228_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementAmendedInFebruary2017WithBayerMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">75</ix:nonFraction> million payment from Bayer. In October 2019, Bayer decided it would advance IONIS-FXI-L<sub>Rx</sub> following positive clinical results. Bayer is now responsible for all global development, regulatory and commercialization activities and costs for the FXI program.</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 eligible to receive up to $<ix:nonFraction name="ions:MaximumAmountOfPaymentsReceivableForLicenseFeesAndMilestones" id="Fact_1ea7b17e0fd54a53ba9ea212e481602c" contextRef="c20201231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMay2015WithBayerMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">385</ix:nonFraction> million in license fees, milestone payments and other payments, including up to $<ix:nonFraction name="ions:MaximumAmountOfPaymentsReceivableForDevelopmentMilestones" id="Fact_e03c5e12d8dc4479948a18adba98b88c" contextRef="c20201231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMay2015WithBayerMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">125</ix:nonFraction> million for the achievement of development milestones and up to $<ix:nonFraction name="ions:MaximumAmountOfPaymentsReceivableForCommercializationMilestones" id="Fact_ab70c484782f41e4acf44792bd373694" contextRef="c20201231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMay2015WithBayerMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">110</ix:nonFraction> million for the achievement of commercialization milestones. In addition, we are eligible to receive tiered royalties in the low to high <ix:nonFraction name="ions:RoyaltyPercentageReceivedOnGrossMarginsOfDrugsUnderCollaborationAgreement" id="Fact_fb2e5156c6b544b98419218e7a28691b" contextRef="c20200101to20201231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMay2015WithBayerMember" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">20</ix:nonFraction> percent range on gross margins of both medicines combined. From inception through December 2020, we have received over $<ix:nonFraction name="ions:CumulativePaymentsReceived" id="Fact_55c7b99eec38441eb299ea5fe41b3ea2" contextRef="c20201231_RangeAxis_MinimumMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMay2015WithBayerMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">185</ix:nonFraction> million from this collaboration. We will achieve the next payment of $<ix:nonFraction name="ions:NextPotentialPayment" id="Fact_abb5e5bfab0742a594537d03e99e580c" contextRef="c20201231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMay2015WithBayerMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">20</ix:nonFraction> million if Bayer initiates a Phase 3 study for the FXI program.</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_1279bd3e4793428181ec1aad1e8b44ba" contextRef="c20150531_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMay2015WithBayerMember" unitRef="U005" decimals="INF" scale="0" format="ixt-sec:numwordsen">three</ix:nonFraction> performance obligations, the license of IONIS-FXI<sub>Rx</sub>, R&amp;D services and delivery of API, all of which we completed in 2016.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In February 2017, when we amended our collaboration with Bayer, we identified <ix:nonFraction name="ions:RevenueFromContractWithCustomerNumberOfNewPerformanceObligations" id="Fact_88bf8c1f8dfc4704bd5e5ef69d1688f0" contextRef="c20170201to20170228_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementAmendedInFebruary2017WithBayerMember" unitRef="U005" decimals="INF" scale="0" format="ixt-sec:numwordsen">two</ix:nonFraction> new performance obligations<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, </span><ix:nonFraction name="ions:RevenueFromContractWithCustomerNumberOfNewPerformanceObligations" id="Fact_036ca3d6a65a45808b611cf2f29cf18c" contextRef="c20170201to20170228_ProductOrServiceAxis_IonisFxiLMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementAmendedInFebruary2017WithBayerMember" unitRef="U005" decimals="INF" scale="0" format="ixt-sec:numwordsen">one</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> for the license of IONIS-FXI-L</span><sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> and </span><ix:nonFraction name="ions:RevenueFromContractWithCustomerNumberOfNewPerformanceObligations" id="Fact_84ed394b95dc4b689089483bec9ee81d" contextRef="c20170201to20170228_ProductOrServiceAxis_ResearchAndDevelopmentServicesForIonisFxiLMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementAmendedInFebruary2017WithBayerMember" unitRef="U005" decimals="INF" scale="0" format="ixt-sec:numwordsen">one</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> for R&amp;D services</span>. We determined the transaction price to be the $<ix:nonFraction name="ions:RevenueFromContractWithCustomerTransactionPrice" id="Fact_c9e8f99e0b5547cfa910d6da0c7fa156" contextRef="c20170228_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementAmendedInFebruary2017WithBayerMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">75</ix:nonFraction> million payment. We allocated $<ix:nonFraction name="ions:RevenueFromContractWithCustomerTransactionPrice" id="Fact_671c15f958d449e1b0996ae26fb02f7f" contextRef="c20170228_ProductOrServiceAxis_IonisFxiLMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementAmendedInFebruary2017WithBayerMember" unitRef="U001" decimals="-5" scale="6" format="ixt:numdotdecimal">64.9</ix:nonFraction> million to <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">the license of IONIS-FXI-L</span><sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> based on its estimated relative stand-alone selling price and recognized the associated revenue upon our delivery of the license in the first quarter of 2017. We allocated $</span><ix:nonFraction name="ions:RevenueFromContractWithCustomerTransactionPrice" id="Fact_66e51b39565d4d5491b40a7ff56ff227" contextRef="c20170228_ProductOrServiceAxis_ResearchAndDevelopmentServicesForIonisFxiLMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMay2015WithBayerMember" unitRef="U001" decimals="-5" scale="6" format="ixt:numdotdecimal">10.1</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million to our R&amp;D services performance obligation based on an estimated relative stand-alone selling price. </span>We recognized revenue for our R&amp;D services performance obligation as we performed services based on our effort to satisfy our performance obligation relative to our total effort expected to satisfy our performance obligation. We completed our obligation in the third quarter 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;">In the fourth quarter of 2019, we earned a $<ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_9fa6b92a37764bc4ad97b1ac44dab174" contextRef="c20191001to20191231_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsBayerMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">10</ix:nonFraction> million milestone payment when Bayer decided it would advance IONIS-FXI-L<sub>Rx</sub>. We recognized this milestone payment in full in the fourth quarter of 2019 because we did not have any performance obligations related to this milestone payment.</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, 2020, 2019 and 2018, we earned the following revenue from our relationship with Bayer (in millions, except percentage amounts):</div>
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<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">F-<span>44</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;">Our consolidated balance sheet at December 31, </span>2020<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> did </span><ix:nonFraction name="us-gaap:ContractWithCustomerLiability" id="Fact_8a8ddd9ea4694b83b23517fa77dd61df" contextRef="c20201231_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsBayerMember" unitRef="U001" decimals="-6" scale="6" format="ixt-sec:numwordsen">no</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">t include any deferred revenue related to our relationship with Bayer. Our </span>consolidated balance sheet at <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">December 31, </span>2019<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_64e74248337d43bd85c81ec53ac919fa" contextRef="c20191231_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsBayerMember" unitRef="U001" decimals="-5" scale="6" format="ixt:numdotdecimal">2.4</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million related to our relationship with Bayer.</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 2010, we entered into an alliance with GSK using our antisense drug discovery platform to discover and develop new medicines against targets for serious and rare diseases, including infectious diseases and some conditions causing blindness. Under the terms of the agreement, we received upfront payments of $<ix:nonFraction name="ions:UpfrontPaymentReceived" id="Fact_7283fa5013cc4c8f8847969829246bd2" contextRef="c20100301to20100331_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGlaxoSmithKlineMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">35</ix:nonFraction> million. Our collaboration with GSK currently includes <ix:nonFraction name="ions:NumberOfMedicinesBeingDeveloped" id="Fact_34359473758b4342a786a2bfd26d9b28" contextRef="c20201231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGlaxoSmithKlineMember" unitRef="U013" decimals="INF" scale="0" format="ixt-sec:numwordsen">two</ix:nonFraction> medicines targeting hepatitis B virus, or HBV: IONIS-HBV<sub>Rx</sub> and IONIS-HBV-L<sub>Rx</sub>. We designed these medicines to reduce the production of viral proteins associated with HBV infection. In the third quarter of 2019, following positive Phase 2 results, GSK licensed our HBV program. GSK is responsible for all global development, regulatory and commercialization activities and costs for the HBV program.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Under our agreement, if GSK successfully develops these medicines and achieves pre-agreed sales targets, we could receive license fees and milestone payments of up to $<ix:nonFraction name="ions:MaximumAmountOfPaymentsReceivableForLicenseFeesAndMilestones" id="Fact_4efd385d112840afad0e4faa46214870" contextRef="c20201231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGlaxoSmithKlineMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">262</ix:nonFraction> million, including up to $<ix:nonFraction name="ions:MaximumAmountOfPaymentsReceivableForDevelopmentMilestones" id="Fact_229776738d884ce8aee54ac341784a2d" contextRef="c20201231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGlaxoSmithKlineMember" unitRef="U001" decimals="-5" scale="6" format="ixt:numdotdecimal">47.5</ix:nonFraction> million for the achievement of development milestones, up to $<ix:nonFraction name="ions:MaximumAmountOfPaymentsReceivableForRegulatoryMilestones" id="Fact_131e23080dcc40398152b2bd4d048056" contextRef="c20201231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGlaxoSmithKlineMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">120</ix:nonFraction> million for the achievement of regulatory milestones and up to $<ix:nonFraction name="ions:MaximumAmountOfPaymentsReceivableForCommercializationMilestones" id="Fact_a5c67dd2e09b4b708ea1ffa029688a59" contextRef="c20201231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGlaxoSmithKlineMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">70</ix:nonFraction> million for the achievement of commercialization milestones. In addition, we are eligible to receive tiered royalties up to the mid-teens on net sales from any product that GSK successfully commercializes under this alliance. From inception through December 2020, we have received more than $<ix:nonFraction name="ions:CumulativePaymentsReceived" id="Fact_80b40aad4e4f428d854cce06e968dea2" contextRef="c20201231_RangeAxis_MinimumMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGlaxoSmithKlineMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">190</ix:nonFraction> million in payments under this alliance with GSK. We will achieve the next payment of $<ix:nonFraction name="ions:NextPotentialPayment" id="Fact_5f7e1c8f371048a4aa050ce4806c0edf" contextRef="c20201231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGlaxoSmithKlineMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">15</ix:nonFraction> million if GSK initiates a Phase 3 study of a medicine under this program.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We completed our R&amp;D services performance obligations under our collaboration in the first quarter of 2015. </span>We identified a new performance obligation when we granted GSK the license of the HBV program and assigned related intellectual property rights in the third quarter of 2019 because the license was distinct from our other performance obligations. We recognized the $<ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_eaf6203cfa224f3791cb9bffe7977090" contextRef="c20190701to20190930_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGlaxoSmithKlineMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">25</ix:nonFraction> million license fee for the HBV program as revenue at that time because GSK had full use of the license without any continuing involvement from us. Additionally, we did not have any further performance obligations related to the license after we delivered it to GSK.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We do not have any remaining performance obligations under our collaboration with GSK; however, we can still earn additional payments and royalties as GSK advances the HBV program.</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, 2020, 2019 and 2018, we earned the following revenue from our relationship with GSK (in millions, except percentage amounts):</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="c20191231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGlaxoSmithKlineMember" unitRef="U001" decimals="-6" scale="6" format="ixt-sec:numwordsen"><ix:nonFraction name="us-gaap:ContractWithCustomerLiability" id="Fact_59e8ee0b0973416987e4c07862acaea5" contextRef="c20201231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGlaxoSmithKlineMember" 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, 2020 and 2019.</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;">Janssen Biotech, Inc.</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 2014, we entered into a collaboration agreement with Janssen Biotech, Inc. to discover and develop antisense medicines that can be locally administered, including oral delivery, to treat autoimmune disorders of the GI tract. Under our collaboration, Janssen is currently advancing ION253 for the treatment of immune-mediated GI disease. Janssen licensed ION253 in the fourth quarter of 2017. Prior to Janssen&#8217;s license of ION253, we were responsible for the discovery activities to identify development candidates. Under the agreement, Janssen is responsible for global development, regulatory and commercialization activities and costs for ION253.</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 $<ix:nonFraction name="ions:UpfrontPaymentReceived" id="Fact_7f98b32d298b42688c37d988ab2909b8" contextRef="c20141201to20141231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2014WithJanssenBiotechIncMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">35</ix:nonFraction> million in upfront payments. We are eligible to receive up to more than $<ix:nonFraction name="ions:MinimumAmountOfPaymentsReceivableForLicenseFeesAndSubstantiveMilestones" id="Fact_a564066b38e84d2595cdfbfc276b1eba" contextRef="c20201231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2014WithJanssenBiotechIncMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">285</ix:nonFraction> million in license fees and milestone payments for these programs, including up to $<ix:nonFraction name="ions:MaximumAmountOfPaymentsReceivableForDevelopmentMilestones" id="Fact_c2e87dcc7db149c7bef875e445a5c48c" contextRef="c20201231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2014WithJanssenBiotechIncMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">65</ix:nonFraction> million for the achievement of development milestones, up to $<ix:nonFraction name="ions:MaximumAmountOfPaymentsReceivableForRegulatoryMilestones" id="Fact_8be6f9afea8a40139feecb8a0aa84941" contextRef="c20201231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2014WithJanssenBiotechIncMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">160</ix:nonFraction> million for the achievement of regulatory milestones and up to $<ix:nonFraction name="ions:MaximumAmountOfPaymentsReceivableForCommercializationMilestones" id="Fact_e21d01127a2247a9ba21d6eafa2cdea6" contextRef="c20201231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2014WithJanssenBiotechIncMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">60</ix:nonFraction> million for the achievement of commercialization milestones. From inception through December 2020, we have received over $<ix:nonFraction name="ions:CumulativePaymentsReceived" id="Fact_9ad34bef7ccb4d00b82f1650470dc23d" contextRef="c20201231_RangeAxis_MinimumMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2014WithJanssenBiotechIncMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">80</ix:nonFraction> million from this collaboration. In addition, we are eligible to receive tiered royalties up to the near teens on net sales from any medicines resulting from this collaboration. We will achieve the next payment of $<ix:nonFraction name="ions:NextPotentialPayment" id="Fact_608263f8b813452282c49861d04ce4b7" contextRef="c20201231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2014WithJanssenBiotechIncMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">5</ix:nonFraction> million if Janssen continues to advance ION253 in development.</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_f68fbf09b9ae48f4837c1876e49a8d0f" contextRef="c20141231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2014WithJanssenBiotechIncMember" unitRef="U005" decimals="INF" scale="0" format="ixt-sec:numwordsen">one</ix:nonFraction> performance obligation, which was to perform R&amp;D services for Janssen. We determined the transaction price to be the $<ix:nonFraction name="ions:RevenueFromContractWithCustomerTransactionPrice" id="Fact_6b929259ee5b4b7da8a05540eca83d56" contextRef="c20141231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2014WithJanssenBiotechIncMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">35</ix:nonFraction> million upfront payments we received. We allocated the <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</span><ix:nonFraction name="ions:RevenueFromContractWithCustomerTransactionPrice" id="Fact_a00a77fdd643486b8ca7e353ece96e57" contextRef="c20141231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2014WithJanssenBiotechIncMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">35</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million</span> to our single performance obligation. As we achieved milestone payments for our R&amp;D services, we included these amounts in our transaction price for our R&amp;D services performance obligation. We recognized revenue for our R&amp;D services performance obligation over our period of performance, which ended in the fourth quarter of 2017.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Under this collaboration, we have also generated additional payments that we concluded were not part of our R&amp;D services performance obligation. We recognized each of these payments in full in the respective quarter in which we generated the payment because the payments were distinct and we did not have any performance obligations for the respective payment. In the third quarter of 2020, we earned a $</span><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_732ff0ca58254e19bd8a20ac7dcdbb03" contextRef="c20200701to20200930_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2014WithJanssenBiotechIncMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">5</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million milestone payment when Janssen initiated a Phase 1 trial for ION253</span>.</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, 2020, 2019 and 2018, we earned the following revenue from our relationship with Janssen (in millions, except percentage amounts):</div>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ConcentrationRiskPercentage1" id="Fact_d89ed37737544e2aac9c1cd3c8d8ab99" contextRef="c20180101to20181231_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2014WithJanssenBiotechIncMember" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">1</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
</table>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We did <ix:nonFraction name="us-gaap:ContractWithCustomerLiability" id="Fact_e6090aaddd3944d880fb682755e83a3b" contextRef="c20191231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2014WithJanssenBiotechIncMember" unitRef="U001" decimals="-6" scale="6" format="ixt-sec:numwordsen"><ix:nonFraction name="us-gaap:ContractWithCustomerLiability" id="Fact_365ae9af3d38401eb562eea4ba20c9d2" contextRef="c20201231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2014WithJanssenBiotechIncMember" unitRef="U001" decimals="-6" scale="6" format="ixt-sec:numwordsen">no</ix:nonFraction></ix:nonFraction>t have any deferred revenue from our relationship with Janssen at December 31, 2020 and 2019.</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;">Novartis</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In January 2017, we initiated a collaboration with Novartis to develop and commercialize pelacarsen and IONIS-APOCIII-L</span><sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">.</span><sub>&#xA0;</sub>We received a $<ix:nonFraction name="ions:UpfrontPaymentReceived" id="Fact_f101e92127dd43ef9f460e172673d2f2" contextRef="c20170101to20170331_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">75</ix:nonFraction> million upfront payment in the first quarter of 2017. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In the first quarter of 2019, Novartis licensed pelacarsen</span> and we earned a $<ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_0515b2fff4b64bc6b94f554c3b656d06" contextRef="c20190101to20190331_ProductOrServiceAxis_LicensingAndOtherRoyaltiesMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">150</ix:nonFraction> million license fee. Novartis is responsible for conducting and funding future development and regulatory activities for pelacarsen, including a global Phase 3 cardiovascular outcomes study that Novartis initiated in the fourth quarter 2019.<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#xA0;</span>In connection with Novartis&#8217; license of pelacarsen, we and Novartis established a more definitive framework under which the companies would negotiate the co-commercialization of pelacarsen in selected markets. Included in this framework is an option by which Novartis could solely commercialize pelacarsen in exchange for Novartis paying us increased sales milestone payments based on sales of pelacarsen.<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#xA0;</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">When Novartis decided to not exercise its option for </span>IONIS-APOCIII-L<sub>Rx</sub>, we retained rights to develop and commercialize IONIS-APOCIII-L<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;">Under the collaboration, we are eligible to receive up to $<ix:nonFraction name="ions:MaximumAmountOfPaymentsReceivableForMilestones" id="Fact_d2d27d33e1b24ff79741dbb8504b3a12" contextRef="c20201231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">675</ix:nonFraction> million in milestone payments, including $<ix:nonFraction name="ions:MaximumAmountOfPaymentsReceivableForDevelopmentMilestones" id="Fact_b0160b60708f4f9cac5ee7648f0ee321" contextRef="c20201231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">25</ix:nonFraction> million for the achievement of a development milestone, up to $<ix:nonFraction name="ions:MaximumAmountOfPaymentsReceivableForRegulatoryMilestones" id="Fact_788a557118454c209aecf3914c029c91" contextRef="c20201231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">290</ix:nonFraction> million for the achievement of regulatory milestones and up to $<ix:nonFraction name="ions:MaximumAmountOfPaymentsReceivableForCommercializationMilestones" id="Fact_b32f437673cc4aac8bfcce020d51b7b0" contextRef="c20201231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">360</ix:nonFraction> million for the achievement of commercialization milestones. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">From inception through December 2020, we have received $</span><ix:nonFraction name="ions:CumulativePaymentsReceived" id="Fact_f70b581c4c184bd7afb533f20dd7fa6d" contextRef="c20201231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">249</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million in upfront payments, milestone payments, license fees and other payments from this collaboration. </span>We are also eligible to receive tiered royalties in the mid-teens to low <ix:nonFraction name="ions:RoyaltyPercentageReceivedOnSalesOfDrug" id="Fact_016f76af44eb49289c02150198f2a523" contextRef="c20200101to20201231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">20</ix:nonFraction> percent range on net sales of pelacarsen. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We</span><span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> will achieve the next payment of $</span><ix:nonFraction name="ions:NextPotentialPayment" id="Fact_3b19b0a102744ca58f85eea2983e6a84" contextRef="c20201231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">25</ix:nonFraction><span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million if Novartis advances 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="c20170101to20170331_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">1.6</ix:nonFraction> million shares of our common stock for $<ix:nonFraction name="ions:ProceedsFromSaleOfCommonStockIncludingPremiumPaid" id="Fact_3a1b3a249b30451fa1ce1c491bcb7999" contextRef="c20170101to20170331_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">100</ix:nonFraction> million in the first quarter of 2017. As part of the SPA, Novartis was required to purchase $<ix:nonFraction name="ions:AdditionalAmountOfCommonStockRequiredToBePurchased" id="Fact_f8120f81bc5b4216ac3b0e47eb07b856" contextRef="c20170331_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">50</ix:nonFraction> million of Akcea&#8217;s common stock at Akcea&#8217;s IPO price or our common stock at a premium if an IPO did not occur by April 2018. Under the SPA, in the second quarter of 2017, Novartis purchased $<ix:nonFraction name="us-gaap:ProceedsFromIssuanceOfPrivatePlacement" id="Fact_47ca08bac8744acbb92fb035975c1a5d" contextRef="c20170401to20170630_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">50</ix:nonFraction> million of Akcea&#8217;s common stock in a separate private placement concurrent with the completion of Akcea&#8217;s IPO at a price per share equal to the IPO price.</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_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember" unitRef="U005" decimals="INF" scale="0" format="ixt-sec:numwordsen">four</ix:nonFraction> separate performance obligations:</div>
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<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="z96b1240939864a0aa59d9ebe41065fe9">
  <tr>
    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">R&amp;D services for pelacarsen;</div></td>
  </tr>
</table>
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<table 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="z3d70c236552f4ba28ef26a97261216f0">
  <tr>
    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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 IONIS-APOCIII-L<sub>Rx</sub>;</div></td>
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<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="ze5c0c7016a924d6cacedb4f5ac960dfd">
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    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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>
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</table>
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<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="zdb1bac79654341e49628adcdaa4ae22a">
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    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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 IONIS-APOCIII-L<sub>Rx</sub>.</div></td>
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</table>
</ix:continuation><ix:continuation id="Text_c14d93f7bfed45529d2c8f535b6f9cbf188" continuedAt="Text_c14d93f7bfed45529d2c8f535b6f9cbf189">
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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 the R&amp;D services for each medicine and the API for each medicine were distinct performance obligations.</div>
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<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">F-<span>46</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 determined our transaction price to be $<ix:nonFraction name="ions:RevenueFromContractWithCustomerTransactionPrice" id="Fact_6dbe3e18253b42678289e91bfc07aa2b" contextRef="c20170331_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember" unitRef="U001" decimals="-5" scale="6" format="ixt:numdotdecimal">108.4</ix:nonFraction> million, comprised of the following:</div>
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<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z121d185a2fd2440eb0afde6cd75e4546">
  <tr>
    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$<ix:nonFraction name="ions:UpfrontPaymentReceived" id="Fact_5578c7a91e964f86994ba7891b038b6c" contextRef="c20170101to20170331_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">75</ix:nonFraction> million from the upfront payment;</div></td>
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</table>
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<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="zb9c0424c697141e98b124b59cc86ef6e">
  <tr>
    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$<ix:nonFraction name="ions:PremiumReceivedOnSharesIssued" id="Fact_a374896a5baf4a14a92524dbf907cb65" contextRef="c20170101to20170331_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember" unitRef="U001" decimals="-5" scale="6" format="ixt:numdotdecimal">28.4</ix:nonFraction> million for the premium paid by Novartis for its purchase of our common stock at a premium in the first quarter of 2017; and</div></td>
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</table>
</ix:continuation><ix:continuation id="Text_c14d93f7bfed45529d2c8f535b6f9cbf195" continuedAt="Text_c14d93f7bfed45529d2c8f535b6f9cbf196">
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z9ccebd2e3ba84fa4b417d18915d23207">
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    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$<ix:nonFraction name="ions:PotentialPremiumReceivedIfCommonStockIsPurchasedInFuture" id="Fact_844ad8b58c81489eb92908f6d9b9a1e0" contextRef="c20170331_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember" unitRef="U001" decimals="-5" scale="6" format="ixt:numdotdecimal">5.0</ix:nonFraction> million for the potential premium Novartis would have paid if they purchased our common stock in the future.</div></td>
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</table>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">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 style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We recognized revenue related to each of the performance obligations as follows:</div>
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<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="z07ee17717ec44cdfadce3eff5cb75de7">
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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 IONIS-APOCIII-L</span><sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> 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: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br /></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_202ff57e88d8402cb5c44dcb77bc2901" contextRef="c20191231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember" unitRef="U001" decimals="-6" scale="6" format="ixt-sec:numwordsen"><ix:nonFraction name="us-gaap:ContractWithCustomerLiability" id="Fact_10f623e4621745d8a337c5cf9f0bb013" contextRef="c20201231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember" unitRef="U001" decimals="-6" scale="6" format="ixt-sec:numwordsen">no</ix:nonFraction></ix:nonFraction>t have any deferred revenue from our relationship with Novartis at December 31, 2020 and 2019.</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;">Pfizer</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 October 2019, we entered into a license agreement with Pfizer for vupanorsen, an investigational medicine in development to treat people with certain cardiovascular diseases. We completed a Phase 2 study of vupanorsen in patients</span> with elevated levels of triglycerides, or hypertriglyceridemia, type 2 diabetes and <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">NAFLD. Pfizer is responsible for all global development, regulatory and commercialization activities and costs for vupanorsen, subject to our right to co-commercialize in the U.S. and certain additional markets.</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;">Under the terms of the agreement, we received a $</span><ix:nonFraction name="ions:UpfrontPaymentReceived" id="Fact_cb6f652ab8d440198d3fd9d76dec5102" contextRef="c20191001to20191031_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2019WithPfizerMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">250</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million upfront payment. We are also eligible to receive development, regulatory and sales milestone payments of up to $</span><ix:nonFraction name="ions:MaximumAmountOfPaymentsReceivableForDevelopmentRegulatoryAndSalesMilestones" id="Fact_6b53e3b0d55a43dc810b7552f975ad24" contextRef="c20201231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2019WithPfizerMember" unitRef="U001" decimals="-8" scale="9" format="ixt:numdotdecimal">1.3</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> billion</span>, including up to $<ix:nonFraction name="ions:MaximumAmountOfPaymentsReceivableForDevelopmentMilestones" id="Fact_4843a345b1a94a5c9754fd3131d466f1" contextRef="c20201231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2019WithPfizerMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">205</ix:nonFraction> million for the achievement of development milestones, up to $<ix:nonFraction name="ions:MaximumAmountOfPaymentsReceivableForRegulatoryMilestones" id="Fact_65c6ae0a577449888f0854e765cc3fca" contextRef="c20201231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2019WithPfizerMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">250</ix:nonFraction> million for the achievement of regulatory milestones and up to $<ix:nonFraction name="ions:MaximumAmountOfPaymentsReceivableForCommercializationMilestones" id="Fact_1e2a222db3b0433380bd4a8b285d7a81" contextRef="c20201231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2019WithPfizerMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">850</ix:nonFraction> million for the achievement of commercialization milestones. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">From inception through December 2020, we have received over $</span><ix:nonFraction name="ions:CumulativePaymentsReceived" id="Fact_19873e3b21b747f88c8366f474fd449b" contextRef="c20201231_RangeAxis_MinimumMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2019WithPfizerMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">330</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million, including a $</span><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_021660c1f7e84a898b8de7c343a2d558" contextRef="c20201001to20201231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2019WithPfizerMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">75</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million milestone payment we earned in the fourth quarter of 2020 when Pfizer began the Phase 2b study of vupanorsen. </span>We are<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> also eligible to earn tiered royalties in the mid-teens to low </span><ix:nonFraction name="ions:RoyaltyPercentageReceivedOnNetSalesOfDrug" id="Fact_087ef4b100ca43ee9a37508169ca8d55" contextRef="c20200101to20201231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2019WithPfizerMember" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">20</ix:nonFraction> percent<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> range on annual worldwide net sales. Prior to regulatory filing for marketing approval, we have the right, at our option to participate in certain commercialization activities with Pfizer in the U.S. and certain additional markets on pre-defined terms and based on meeting pre-defined criteria. 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:NextPotentialPayment" id="Fact_ba59193a12cb4ecfa5c7841f81370632" contextRef="c20201231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2019WithPfizerMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">50</ix:nonFraction><span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million if Pfizer advances vupanorsen.</span></div>
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<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">F-<span>47</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 the license agreement, we identified <ix:nonFraction name="ions:RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations" id="Fact_a8154dd63afb404880837533d573e4e5" contextRef="c20191031_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2019WithPfizerMember" unitRef="U005" decimals="INF" scale="0" format="ixt-sec:numwordsen">three</ix:nonFraction> separate performance obligations:</div>
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<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="zd5bad646b7e448a3a9fe0f3ca3c6c245">
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    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">License of vupanorsen;</div></td>
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<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="z0f346714db2e4d08bcd013533066c0cc">
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    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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 vupanorsen; and</div></td>
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<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="ze9f95e2f073b4cbf8e0854f2741778f8">
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    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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 vupanorsen.</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 determined the transaction price to be $<ix:nonFraction name="ions:RevenueFromContractWithCustomerTransactionPrice" id="Fact_0a949aa4d4bd4639afc9cb68a2386c63" contextRef="c20191031_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2019WithPfizerMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">250</ix:nonFraction> million, the upfront payment we received.<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> We </span>allocated the transaction price based on the estimated stand-alone selling price of each performance obligation as follows:</div>
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<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z41311be7633d461192f4fe74ca293c01">
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    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$<ix:nonFraction name="ions:RevenueFromContractWithCustomerTransactionPrice" id="Fact_3df59de76eec44fb982aa66ddb7bf65b" contextRef="c20191031_ProductOrServiceAxis_VupanorsenMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2019WithPfizerMember" unitRef="U001" decimals="-5" scale="6" format="ixt:numdotdecimal">245.6</ix:nonFraction> million for the license of vupanorsen;</div></td>
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<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="z4e228f251e304158a2d73dced6a689f4">
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    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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;">$</span><ix:nonFraction name="ions:RevenueFromContractWithCustomerTransactionPrice" id="Fact_2ee33180ebd4466188789fc4e1ca515e" contextRef="c20191031_ProductOrServiceAxis_ResearchAndDevelopmentServicesForVupanorsenMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2019WithPfizerMember" unitRef="U001" decimals="-5" scale="6" format="ixt:numdotdecimal">2.2</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million for the R&amp;D services for </span>vupanorsen<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">; and</span></div></td>
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<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z09d754cd2883400894b04f43113ed981">
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    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</span><ix:nonFraction name="ions:RevenueFromContractWithCustomerTransactionPrice" id="Fact_7dab3971bd6d482b92da849fa5460d11" contextRef="c20191031_ProductOrServiceAxis_VupanorsenActivePharmaceuticalIngredientMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2019WithPfizerMember" unitRef="U001" decimals="-5" scale="6" format="ixt:numdotdecimal">2.2</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million for the delivery of </span>vupanorsen<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> API.</span></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 related to each of our performance obligations as follows:</div>
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<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="z5049f3a6226d4187bf650e164ea1c247">
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    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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 recognized $<ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_a58f0662a0494f9fbe63a6f7245c7574" contextRef="c20191001to20191231_ProductOrServiceAxis_VupanorsenMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2019WithPfizerMember" unitRef="U001" decimals="-5" scale="6" format="ixt:numdotdecimal">245.6</ix:nonFraction> million for the license of vupanorsen in the fourth quarter of 2019 because we determined the license we granted to Pfizer was distinct from our other performance obligations and Pfizer had full use of the license without any continuing involvement from us.</div></td>
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<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="z371608c9e0fe48d3a2f97c25050c0b35">
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    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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 <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">recognized revenue related to the R&amp;D services for </span>vupanorsen<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> as we performed services </span>based on our effort to satisfy our performance obligation relative to our total effort to satisfy our performance obligation<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. We completed our R&amp;D services in </span>mid-2020<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">.</span></div></td>
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<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="zcf939c7c945446388558c20dd6e65f46">
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    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> recognized the amount attributed to the API supply for </span>vupanorsen<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> when we delivered it to Pfizer in the fourth quarter of 2019.</span></div></td>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In the fourth quarter of 2020, we earned a $<ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_e437ffd3cb564b239e149a2aa1e038e4" contextRef="c20201001to20201231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2019WithPfizerMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">75</ix:nonFraction> million milestone payment when Pfizer began the Phase 2b study of vupanorsen. We recognized this milestone payment in full in the fourth quarter of 2020 because we did not have any performance obligations related to this milestone payment.</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, 2020 and 2019, we earned the following revenue from our relationship with Pfizer (in millions, except percentage 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 did </span><ix:nonFraction name="us-gaap:ContractWithCustomerLiability" id="Fact_ebd22b3448b04409b2309232c0a9ba00" contextRef="c20201231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2019WithPfizerMember" unitRef="U001" decimals="-6" scale="6" format="ixt-sec:numwordsen">no</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">t have any deferred revenue from our relationship with Pfizer at December 31, </span>2020<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. Our </span>consolidated balance sheet at <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">December 31, 2019 included deferred revenue of $</span><ix:nonFraction name="us-gaap:ContractWithCustomerLiability" id="Fact_760c728f58ed437babeba99d7d49729c" contextRef="c20191231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2019WithPfizerMember" unitRef="U001" decimals="-5" scale="6" format="ixt:numdotdecimal">1.3</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million related to our relationship with Pfizer.</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;">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;">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 up to $<ix:nonFraction name="ions:MaximumPaymentReceivableUnderLicenseAgreement" id="Fact_7e14ae5c11c740c6831238a4f01ae711" contextRef="c20201231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInAugust2018WithPtcTherapeuticsMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">26</ix:nonFraction> million in payments. From inception through December 2020, we have received $<ix:nonFraction name="ions:CumulativePaymentsReceived" id="Fact_0c7e746376f2421b95a9ee64b3d4f485" contextRef="c20201231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInAugust2018WithPtcTherapeuticsMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">22</ix:nonFraction> million from PTC. We are eligible to receive royalties from PTC in the mid-<ix:nonFraction name="ions:RoyaltyPercentageReceivedOnNetSalesOfEachDrugInLatinAmericaFromCollaborationPartner" id="Fact_570d071a48d248dbb4cd460b720cd572" contextRef="c20200101to20201231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInAugust2018WithPtcTherapeuticsMember" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">20</ix:nonFraction> percent range on net sales in Latin America for each medicine. PTC&#8217;s obligation to pay us royalties begins on the earlier of <ix:nonNumeric name="ions:PeriodBeforeCollaborationPartnerPaysRoyaltiesOnNetSalesOfProductAfterFirstCommercialSaleInBrazil" id="Fact_bccc4622e6f241879d241b2230aae36c" contextRef="c20200101to20201231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInAugust2018WithPtcTherapeuticsMember" format="ixt-sec:durmonth">12</ix:nonNumeric> months after the first commercial sale of a product in Brazil or the date that PTC recognizes revenue of at least $<ix:nonFraction name="ions:RevenueRecognizedByCollaborationPartnerInLatinAmericaBeforePayingRoyalties" id="Fact_bc71f4a0dda144cc9da7727f9004032f" contextRef="c20200101to20201231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInAugust2018WithPtcTherapeuticsMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">10</ix:nonFraction> million in Latin America.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In the third quarter of 2018 at the commencement of this collaboration, we identified <ix:nonFraction name="ions:RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations" id="Fact_7cdf5da28b2f42cbb5b3b1e421c304b3" contextRef="c20180831_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInAugust2018WithPtcTherapeuticsMember" unitRef="U005" decimals="INF" scale="0" format="ixt-sec:numwordsen">two</ix:nonFraction> performance obligations, which were the licenses we granted to PTC to commercialize TEGSEDI and WAYLIVRA in Latin America and certain Caribbean countries. We recognized $<ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_cca90ebf4c4e4f7eb1bd74a11a6216ea" contextRef="c20180701to20180930_ProductOrServiceAxis_LicensingAndOtherRoyaltiesMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInAugust2018WithPtcTherapeuticsMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">12</ix:nonFraction> million in license fee revenue at that time because PTC had full use of both licenses without any continuing involvement from us. We do not have any remaining performance obligations under our collaboration with PTC. We can still earn additional payments and royalties as PTC commercializes TEGSEDI and WAYLIVRA.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Under this collaboration, we have also generated milestone payments that we concluded were not part of the performance obligations discussed above. We recognized each of these milestone payments in full in the respective quarter in which we achieved the milestone payment because the payments were distinct and we did not have any performance obligations for the respective payment. The following are the payments we have earned:</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, 2020, 2019 and 2018, we earned the following revenue from our relationship with PTC (in millions, except percentage amounts):</div>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 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;">Our consolidated balance sheet at December 31, 2020 and 2019 did <ix:nonFraction name="us-gaap:ContractWithCustomerLiability" id="Fact_dd80a9f419024a63bbffa3c2e2888698" contextRef="c20191231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInAugust2018WithPtcTherapeuticsMember" unitRef="U001" decimals="-6" scale="6" format="ixt-sec:numwordsen"><ix:nonFraction name="us-gaap:ContractWithCustomerLiability" id="Fact_81d977bc02a14b74be1bb00b1a4c83a5" contextRef="c20201231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInAugust2018WithPtcTherapeuticsMember" unitRef="U001" decimals="-6" scale="6" format="ixt-sec:numwordsen">no</ix:nonFraction></ix:nonFraction>t include any deferred revenue related to our relationship with PTC.</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;">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 April 2013, we formed an alliance with Hoffman-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 in Phase 3 development. We developed tominersen through completion of our Phase 1/2 clinical study in people with early stage HD. In the fourth quarter of 2017, upon completion of the Phase 1/2 study, Roche exercised its option to license tominersen. Roche is responsible for all global development, regulatory and commercialization activities and costs for tominersen.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Under the terms of the agreement, we received an upfront payment of $<ix:nonFraction name="ions:UpfrontPaymentReceived" id="Fact_9f09a173393d49bc818e79aacee84764" contextRef="c20130401to20130430_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">30</ix:nonFraction> million in April 2013 and an additional $<ix:nonFraction name="ions:MilestonePaymentsReceived" id="Fact_8432cd12b85e48c6b111a7bdcb5f2ac8" contextRef="c20170101to20171231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">3</ix:nonFraction> million payment in 2017. We are eligible to receive up to $<ix:nonFraction name="ions:MaximumAmountOfPaymentsReceivableForLicenseFeesAndMilestones" id="Fact_d8d42ebb32dc46b7895c83156cf73607" contextRef="c20201231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">365</ix:nonFraction> million in a license fee and milestone payments including up to $<ix:nonFraction name="ions:MaximumAmountOfPaymentsReceivableForDevelopmentMilestones" id="Fact_70a5f7bc239446719e9285ed2ff78c07" contextRef="c20201231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">70</ix:nonFraction> million for the achievement of development milestones, up to $<ix:nonFraction name="ions:MaximumAmountOfPaymentsReceivableForRegulatoryMilestones" id="Fact_884490256579410c93629768255d304a" contextRef="c20201231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">170</ix:nonFraction> million for the achievement of regulatory milestones and up to $<ix:nonFraction name="ions:MaximumAmountOfPaymentsReceivableForCommercializationMilestones" id="Fact_a9fce437f8684220b259d8408d43875f" contextRef="c20201231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">80</ix:nonFraction> million for the achievement of commercialization milestones. In addition, we are eligible to receive up to $<ix:nonFraction name="ions:MaximumAmountOfPaymentReceivableForEachAdditionalDrugDeveloped" id="Fact_67793d8d7c8843aba2b236e8d909758e" contextRef="c20201231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember" unitRef="U001" decimals="-5" scale="6" format="ixt:numdotdecimal">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 any net sales of any product resulting from this alliance. From inception through December 2020, we have received $<ix:nonFraction name="ions:CumulativePaymentsReceived" id="Fact_3aa74885781e415aa4fe5dd8e04e1eda" contextRef="c20201231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">150</ix:nonFraction> million in upfront fees, milestone payments and license fees under this collaboration. We will achieve the next payment of $<ix:nonFraction name="ions:NextPotentialPayment" id="Fact_cb403b59db80408fb4a9b96e8393b762" contextRef="c20201231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">15</ix:nonFraction> million if Roche advances tominersen.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">At the commencement of this collaboration, we identified <ix:nonFraction name="ions:RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations" id="Fact_efae3e04708b4937bacd7fa2bb5963f7" contextRef="c20130430_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember" unitRef="U005" decimals="INF" scale="0" format="ixt-sec:numwordsen">one</ix:nonFraction> performance obligation, which was to perform R&amp;D services for Roche. We determined the transaction price to be the $<ix:nonFraction name="ions:RevenueFromContractWithCustomerTransactionPrice" id="Fact_872b6a5c29be484ca3beb5fa683f1784" contextRef="c20130430_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">30</ix:nonFraction> million upfront payment we received and allocated it to our single performance obligation. As we achieved milestone payments for our R&amp;D services, we included these amounts in our transaction price for our R&amp;D services performance obligation. We recognized revenue for our R&amp;D services performance obligation over our period of performance, which ended in the third quarter of 2017.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Under this collaboration, we have also generated additional payments that we concluded were not part of our R&amp;D services performance obligation. We recognized each of these payments in full in the respective quarter in which we generated the payment because the payments were distinct and we did not have any performance obligations for the respective payment. The following are the payments we have earned:</div>
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<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="zf451f16441ea44558aa69cebef8e1675">
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    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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 fourth quarter of 2017, we earned a $<ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_bc4e255dadbd4cddaaf6cf364d7f60a2" contextRef="c20171001to20171231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">45</ix:nonFraction> million license fee when Roche licensed tominersen because Roche had full use of the license without any continuing involvement from us.</div></td>
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<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="z00ac98db4efa4864b5d2fa1574c1fc7f">
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    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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 first quarter of 2019, we earned $<ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_7314f04e9d0e40a49fbaacf4f47109de" contextRef="c20190101to20190331_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">35</ix:nonFraction> million in milestone payments when Roche dosed the first patient in the Phase 3 study of tominersen in the first quarter of 2019.</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 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: 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 October 2018, we entered into a collaboration agreement with Roche to</span><span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> develop IONIS-FB-L</span><sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> for the treatment of complement-mediated diseases. We are currently conducting Phase 2 studies in </span><ix:nonFraction name="ions:NumberOfDiseaseIndications" id="Fact_748d8e6ad1bb43a384bba3995dac28ea" contextRef="c20200101to20201231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember" unitRef="U017" decimals="INF" scale="0" format="ixt-sec:numwordsen">two</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> disease indications for </span><span style="background-color: #FBFBFB; 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;">, </span><ix:nonFraction name="ions:NumberOfDiseaseIndications" id="Fact_33191bc87cff451284262a2fbdef6e22" contextRef="c20200101to20201231_ProductOrServiceAxis_GeographicAtrophyMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember" unitRef="U017" decimals="INF" scale="0" format="ixt-sec:numwordsen">one</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> for the treatment of patients with GA, the advanced stage of dry AMD, and a </span><span style="-sec-ix-hidden:Fact_04500eaf787641bfbd86183ba9891b89">second</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> for the treatment of patients with IgA nephropathy. </span>Roche<span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> has the option to license 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;"> at the completion of these studies. Upon licensing, </span>Roche <span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">will be responsible for global development, regulatory and commercialization activities and 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;"><span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Under the terms of this agreement, we received a </span>$<ix:nonFraction name="ions:UpfrontPaymentReceived" id="Fact_dc2c32a9c1124cddb9ed5ff336ece731" contextRef="c20181001to20181231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">75</ix:nonFraction> million<span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> upfront payment in the fourth quarter of 2018. We are eligible to receive up to </span>$<ix:nonFraction name="ions:MaximumAmountOfPaymentsReceivableForLicenseFeesAndMilestones" id="Fact_06d83477fcf046bbabd2d4017da3a520" contextRef="c20201231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">684</ix:nonFraction> million<span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> in development, regulatory and sales milestone payments and license fees. In addition, we are also eligible to receive tiered royalties from the high teens to </span><ix:nonFraction name="ions:RoyaltyPercentageReceivedOnNetSalesOfDrug" id="Fact_63fb5f4decbb426a9cd241023b3ecd39" contextRef="c20200101to20201231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">20</ix:nonFraction> percent<span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> on net sales. We will achieve the next payment of $</span><ix:nonFraction name="ions:NextPotentialPayment" id="Fact_5128247561064475b51c4c5bf62130be" contextRef="c20201231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">20</ix:nonFraction><span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million if we advance </span>the Phase 2 study in patients with dry AMD<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;">At the commencement of this collaboration, we identified <ix:nonFraction name="ions:RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations" id="Fact_468a8db7e8de46a69b5ee7a0575f664d" contextRef="c20181031_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember" unitRef="U005" decimals="INF" scale="0" format="ixt-sec:numwordsen">one</ix:nonFraction> performance obligation, which was to perform R&amp;D services for Roche. We determined the transaction price to be the $<ix:nonFraction name="ions:RevenueFromContractWithCustomerTransactionPrice" id="Fact_64f9009b51e54bc8a818455d38bda2ae" contextRef="c20181031_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">75</ix:nonFraction> million upfront payment we received and allocated it to our single performance obligation. We are recognizing revenue for our R&amp;D services performance obligation as we perform services based on our effort to satisfy our performance obligation relative to our total effort expected to satisfy our performance obligation. During the fourth quarter of 2020, we <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">updated our estimate of the total effort we expected to expend to satisfy our performance obligation under this collaboration.</span>&#xA0;<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In the fourth quarter of 2020, we recorded a cumulative catch up adjustment of $</span><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_0c806f7d3c2b4f6d9c6f41c84e900bd0" contextRef="c20201001to20201231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember" unitRef="U001" decimals="-5" scale="6" sign="-" format="ixt:numdotdecimal">9.2</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million to decrease revenue because we updated our total cost estimate to complete the Phase 2 study of </span><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 the </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">treatment of patients with GA. </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 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 years ended December 31, 2020, 2019 and 2018, we earned the following revenue from our relationship with Roche (in millions, except percentage 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;">Our </span>consolidated balance sheet at <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">December 31, </span>2020<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> and </span>2019<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="c20201231_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsRocheMember" unitRef="U001" decimals="-5" scale="6" format="ixt:numdotdecimal">47.2</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million and $</span><ix:nonFraction name="us-gaap:ContractWithCustomerLiability" id="Fact_a38902f403274142aedd7c7ed42e8214" contextRef="c20191231_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsRocheMember" unitRef="U001" decimals="-5" scale="6" format="ixt:numdotdecimal">52.3</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; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Alnylam Pharmaceuticals, Inc.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Under the terms of our agreement with Alnylam, we exclusively licensed to Alnylam our patent estate relating to antisense motifs and mechanisms and oligonucleotide chemistry for double-stranded RNAi therapeutics in exchange for 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 rights to 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 medicines 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>
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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, 2020 and 2019 did <ix:nonFraction name="us-gaap:ContractWithCustomerLiability" id="Fact_87589be5c6de472fa7c2f37215199412" contextRef="c20191231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2004WithAlnylamPharmaceuticalsIncMember" unitRef="U001" decimals="-6" scale="6" format="ixt-sec:numwordsen"><ix:nonFraction name="us-gaap:ContractWithCustomerLiability" id="Fact_12c9599416c543e7890f0ee3f45418ed" contextRef="c20201231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2004WithAlnylamPharmaceuticalsIncMember" unitRef="U001" decimals="-6" scale="6" format="ixt-sec:numwordsen">no</ix:nonFraction></ix:nonFraction>t include any deferred revenue related to our relationship with Alnylam.</div>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">7. Akcea Acquisition</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;">Purchase Price and Direct Transaction Costs Accounting for the Akcea Acquisition</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 2020, we acquired the shares of Akcea&#8217;s common stock we did not own, increasing our ownership from <ix:nonFraction name="us-gaap:MinorityInterestOwnershipPercentageByParent" id="Fact_b6feac506d324b98951f0933ce40dd67" contextRef="c20200930_OwnershipAxis_AkceaTherapeuticsIncMember" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">76</ix:nonFraction> percent to <ix:nonFraction name="us-gaap:MinorityInterestOwnershipPercentageByParent" id="Fact_33b44fc190674e72a94a538abf61155f" contextRef="c20201031_OwnershipAxis_AkceaTherapeuticsIncMember" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">100</ix:nonFraction> percent. Under the purchase agreement, we purchased <ix:nonFraction name="ions:ConsolidationLessThanWhollyOwnedSubsidiaryParentOwnershipInterestChangesPurchaseOfInterestByParentShares" id="Fact_24aa2fc2d1384378a728edf162abb8fb" contextRef="c20201001to20201031_OwnershipAxis_AkceaTherapeuticsIncMember" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">24.8</ix:nonFraction> million shares at $<ix:nonFraction name="ions:ConsolidationLessThanWhollyOwnedSubsidiaryParentOwnershipInterestChangesPurchaseOfInterestByParentPricePerShare" id="Fact_fa704d2a69a948088d5d227df198df4e" contextRef="c20201001to20201031_OwnershipAxis_AkceaTherapeuticsIncMember" unitRef="U004" decimals="2" scale="0" format="ixt:numdotdecimal">18.15</ix:nonFraction> per share, resulting in a total purchase price of $<ix:nonFraction name="us-gaap:ConsolidationLessThanWhollyOwnedSubsidiaryParentOwnershipInterestChangesPurchaseOfInterestByParent" id="Fact_2e6fddec0b5647c1862613421ea983f3" contextRef="c20201001to20201031_OwnershipAxis_AkceaTherapeuticsIncMember" unitRef="U001" decimals="-5" scale="6" format="ixt:numdotdecimal">450.6</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;">To reflect our <ix:nonFraction name="us-gaap:MinorityInterestOwnershipPercentageByParent" id="Fact_43cd203825e04ef79c3027298eeb9ffa" contextRef="c20201031_OwnershipAxis_AkceaTherapeuticsIncMember" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">100</ix:nonFraction> percent ownership, we accounted for the increase in our ownership by eliminating the noncontrolling interest adjustment in stockholders&#8217; equity in accordance with the Consolidation accounting guidance (ASC Topic 810). We recognized the difference between the purchase price and the adjustment to noncontrolling interest in stockholders&#8217; equity as additional-paid-in capital. Refer to our <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Statement of Stockholders&#8217; Equity</span> for detailed amounts.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We accounted for the transaction costs related to the Akcea Acquisition as a direct charge to stockholders&#8217; equity. We incurred $<ix:nonFraction name="us-gaap:BusinessAcquisitionCostOfAcquiredEntityTransactionCosts" id="Fact_0884cfbdf1684305809ccf99311b4099" contextRef="c20201231_OwnershipAxis_AkceaTherapeuticsIncMember" unitRef="U001" decimals="-5" scale="6" format="ixt:numdotdecimal">40.6</ix:nonFraction> million of direct transaction costs from the Akcea Acquisition, primarily comprised of banking and legal fees.</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;">Equity Award Payouts related to the Akcea Acquisition</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 October 2020, as part of the Akcea Acquisition, Ionis cancelled all of Akcea&#8217;s equity awards. In exchange for the cancelled awards, if eligible under the terms of the Acquisition, we paid holder&#8217;s a cash payment. We paid $</span><ix:nonFraction name="ions:CashPurchasePriceOfEquityAwards" id="Fact_638c1e20e6404ff4aa52f098c6deb05d" contextRef="c20201001to20201231_OwnershipAxis_AkceaTherapeuticsIncMember" unitRef="U004" decimals="2" scale="0" format="ixt:numdotdecimal">18.15</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> for each outstanding RSU. For each outstanding option with an exercise price less than $</span><ix:nonFraction name="ions:CashPurchasePriceOfEquityAwards" id="Fact_b89bdecf0fa14315963911cf431521b4" contextRef="c20201001to20201231_OwnershipAxis_AkceaTherapeuticsIncMember" unitRef="U004" decimals="2" scale="0" format="ixt:numdotdecimal">18.15</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, we paid $</span><ix:nonFraction name="ions:CashPurchasePriceOfEquityAwards" id="Fact_99ca9852ab9f4ad6ae3ea6c3a7b75b3b" contextRef="c20201001to20201231_OwnershipAxis_AkceaTherapeuticsIncMember" unitRef="U004" decimals="2" scale="0" format="ixt:numdotdecimal">18.15</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> less the exercise price. As a result, we paid out $</span><ix:nonFraction name="ions:PaymentsForCancelledEquityAwards" id="Fact_aab524f795c14b308413d9edfc049700" contextRef="c20201001to20201231_OwnershipAxis_AkceaTherapeuticsIncMember" unitRef="U001" decimals="-5" scale="6" format="ixt:numdotdecimal">53.4</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million in the fourth quarter of 2020 related to Akcea&#8217;s cancelled equity awards. We accounted for these payments as part of the transaction costs recorded to stockholders&#8217; equity in the fourth quarter of 2020. </span>Because we did not replace the Akcea awards, we recognized all unrecognized non-cash stock-based compensation ($<ix:nonFraction name="us-gaap:EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions" id="Fact_46135659ff5e45719f62bc97882f97ae" contextRef="c20201031_OwnershipAxis_AkceaTherapeuticsIncMember" unitRef="U001" decimals="-5" scale="6" format="ixt:numdotdecimal">59.3</ix:nonFraction> million) under Akcea&#8217;s Plan in our statement of operations in the post-acquisition period in the fourth quarter of 2020.</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;">Severance and Retention Costs related to the Akcea Acquisition</div>
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<div style="text-align: justify; text-indent: 36pt; margin-top: 2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">As a result of the Akcea Acquisition, we expect to incur severance expenses of up to $<ix:nonFraction name="us-gaap:RestructuringAndRelatedCostExpectedCost1" id="Fact_26b929fece654080a789180795d558de" contextRef="c20201231_RangeAxis_MaximumMember_RestructuringCostAndReserveAxis_AkceaAcquisitionEmployeeSeveranceMember" unitRef="U001" decimals="-5" scale="6" format="ixt:numdotdecimal">9.3</ix:nonFraction> million and retention expenses of up to $<ix:nonFraction name="us-gaap:RestructuringAndRelatedCostExpectedCost1" id="Fact_ece2061620284b679520534ba60bc0be" contextRef="c20201231_RangeAxis_MaximumMember_RestructuringCostAndReserveAxis_AkceaAcquisitionEmployeeRetentionMember" unitRef="U001" decimals="-5" scale="6" format="ixt:numdotdecimal">19.2</ix:nonFraction> million. During the fourth quarter of 2020, we recorded $<ix:nonFraction name="us-gaap:RestructuringCharges" id="Fact_a12fd6176d8a4d61a8a5848e09148cd1" contextRef="c20201001to20201231_RestructuringCostAndReserveAxis_AkceaAcquisitionEmployeeSeveranceAndRetentionMember" unitRef="U001" decimals="-5" scale="6" format="ixt:numdotdecimal">15.3</ix:nonFraction> million of severance and retention related costs in operating expenses. We will recognize the remaining severance and retention costs through October 2021.</div>
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<div style="text-align: justify; text-indent: 36pt; margin-top: 2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following table summarizes the costs by category related to the Akcea Acquisition (in millions):</div>
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  <tr>
    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"></div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Three Months Ended</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">December 31, 2020</div></td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RestructuringCharges" id="Fact_632b4ea945604eb682b56b7a5cc7f9af" contextRef="c20201001to20201231_IncomeStatementLocationAxis_ResearchAndDevelopmentExpensesMember_RestructuringCostAndReserveAxis_AkceaAcquisitionEmployeeSeveranceAndRetentionMember" unitRef="U001" decimals="-5" scale="6" format="ixt:numdotdecimal">3.9</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
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    <td valign="bottom" style="vertical-align: bottom; width: 88%; padding-bottom: 2px;"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">SG&amp;A expenses</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RestructuringCharges" id="Fact_4a10b83e0c37473c8312af06e2a989dc" contextRef="c20201001to20201231_IncomeStatementLocationAxis_SellingGeneralAndAdministrativeExpensesMember_RestructuringCostAndReserveAxis_AkceaAcquisitionEmployeeSeveranceAndRetentionMember" unitRef="U001" decimals="-5" scale="6" format="ixt:numdotdecimal">11.4</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
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    <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</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RestructuringCharges" id="Fact_a53f417019c5445ea45a0e1f95f39a1b" contextRef="c20201001to20201231_RestructuringCostAndReserveAxis_AkceaAcquisitionEmployeeSeveranceAndRetentionMember" unitRef="U001" decimals="-5" scale="6" format="ixt:numdotdecimal">15.3</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
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<div style="text-align: justify; text-indent: 36pt; margin-top: 2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following table summarizes the severance and retention reserve included in accrued compensation for the period indicated related to Akcea Acquisition (in millions):</div>
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<table cellpadding="0" cellspacing="0" id="z320d5d0099aa41cba26e4938ee44b076" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
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    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"></div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Three Months Ended</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">December 31, 2020</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
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    <td valign="bottom" style="vertical-align: top; width: 88%; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Severance &amp; retention reserve beginning balance</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RestructuringReserve" id="Fact_ddb95474499a43a38b47938bf73480f8" contextRef="c20200930_RestructuringCostAndReserveAxis_AkceaAcquisitionEmployeeSeveranceAndRetentionMember" unitRef="U001" decimals="-6" scale="6" format="ixt:zerodash">&#8212;</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
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    <td valign="bottom" style="vertical-align: top; width: 88%;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Severance &amp; retention expensed during period</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RestructuringCharges" id="Fact_78d62616130249a788e7a908f82a20a2" contextRef="c20201001to20201231_RestructuringCostAndReserveAxis_AkceaAcquisitionEmployeeSeveranceAndRetentionMember" unitRef="U001" decimals="-5" scale="6" format="ixt:numdotdecimal">15.3</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
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    <td valign="bottom" style="vertical-align: top; width: 88%; padding-bottom: 2px; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Amounts paid during the period</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:PaymentsForRestructuring" id="Fact_e3c59bd9264043e395b330bcb3edcef0" contextRef="c20201001to20201231_RestructuringCostAndReserveAxis_AkceaAcquisitionEmployeeSeveranceAndRetentionMember" unitRef="U001" decimals="-5" scale="6" format="ixt:numdotdecimal">0.6</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
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    <td valign="bottom" style="vertical-align: top; width: 88%; padding-bottom: 4px;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Severance &amp; retention reserve ending balance</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RestructuringReserve" id="Fact_b335aec5430c4aea9f84c442ed946f9a" contextRef="c20201231_BalanceSheetLocationAxis_EmployeeRelatedLiabilitiesCurrentMember_RestructuringCostAndReserveAxis_AkceaAcquisitionEmployeeSeveranceAndRetentionMember" unitRef="U001" decimals="-5" scale="6" format="ixt:numdotdecimal">14.7</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">8. Severance and Retention Costs related to our Restructured European Operations</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 the fourth quarter of 2020, </span>we entered into a distribution agreement with Sobi to commercialize TEGSEDI and WAYLIVRA in Europe. Under the distribution agreement, Sobi took over all material distribution operations at the end of January 2021. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We remain the marketing authorization holder for TEGSEDI and WAYLIVRA in Europe. We will continue to maintain limited European operations including regulatory, manufacturing, and the management of relationships with key opinion leaders. We will also continue to lead the TEGSEDI and WAYLIVRA global commercial strategy.</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 a result of this change, we expect to incur up to $<ix:nonFraction name="us-gaap:RestructuringAndRelatedCostExpectedCost1" id="Fact_2a74105eea194c3287e81514aa839527" contextRef="c20201231_RangeAxis_MaximumMember_RestructuringCostAndReserveAxis_UpdatedEuropeanDistributionModelEmployeeSeveranceAndRetentionMember" unitRef="U001" decimals="-5" scale="6" format="ixt:numdotdecimal">14.8</ix:nonFraction> million of severance and retention expenses. During the fourth quarter of 2020, we recorded $<ix:nonFraction name="us-gaap:RestructuringCharges" id="Fact_ac151d77af0549aa963b0bc394117861" contextRef="c20201001to20201231_RestructuringCostAndReserveAxis_UpdatedEuropeanDistributionModelEmployeeSeveranceAndRetentionMember" unitRef="U001" decimals="-5" scale="6" format="ixt:numdotdecimal">12.5</ix:nonFraction> million of severance and retention related costs in operating expenses related to this agreement. We will recognize the remaining expenses through October 2021, of which we will recognize the majority of the remaining expenses in the first quarter of 2021.</div>
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<div style="text-align: justify;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> </span><br /></div>
</ix:continuation><ix:nonNumeric name="us-gaap:ScheduleOfRestructuringAndRelatedCostsTextBlock" id="Text_f2df1e72e7314af39e867699554af81d" contextRef="c20200101to20201231" escape="true" continuedAt="Text_91756cc1f3ac4442a238673151f7fdf31"><ix:continuation id="Text_3eaeb34ab1424158aed65885d07cbd1e6" continuedAt="Text_3eaeb34ab1424158aed65885d07cbd1e7">
<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 costs by category related to our restructured European operations (in millions):</div>
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<div style="text-align: justify;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> </span><br /></div>
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  <tr>
    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"></div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Three Months Ended</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">December 31, 2020</div></td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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<div><br /></div>
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<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following table summarizes the severance and retention reserve included in accrued compensation for the periods indicated related to our restructured European operations (in millions):</div>
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<div style="text-align: justify;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> </span><br /></div>
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  <tr>
    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"></div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Three Months Ended</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">December 31, 2020</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: top; width: 88%; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Severance &amp; retention reserve beginning balance</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: top; width: 88%;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Severance &amp; retention expensed during period</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RestructuringCharges" id="Fact_523f6a352a20442397b200bb597b61b1" contextRef="c20201001to20201231_RestructuringCostAndReserveAxis_UpdatedEuropeanDistributionModelEmployeeSeveranceAndRetentionMember" unitRef="U001" decimals="-5" scale="6" format="ixt:numdotdecimal">12.5</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: top; width: 88%; padding-bottom: 2px; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Amounts paid during the period</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;"><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: 4px;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Severance &amp; retention reserve ending balance</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>
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</table>
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<div style="text-align: left;"><br /></div>
<div><ix:nonNumeric name="us-gaap:SegmentReportingDisclosureTextBlock" id="Text_2b6a002acca646b0906b3570ab8ac869" contextRef="c20200101to20201231" escape="true" continuedAt="Text_a097c162b67d4481a4b05090ec96a7d01">
<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">9. Segment Information and Concentration of Business Risk</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Through 2020, we had <ix:nonFraction name="us-gaap:NumberOfReportableSegments" id="Fact_7b6216c3ebc44b518de52c3d575b97de" contextRef="c20200101to20201231" unitRef="U009" decimals="INF" scale="0" format="ixt-sec:numwordsen">two</ix:nonFraction> reportable segments, our Ionis Core segment and Akcea Therapeutics. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We have provided segment financial information and results for our Ionis Core segment and our Akcea Therapeutics segment based on the segregation of revenues and expenses that our chief decision maker reviewed to assess operating performance and to make operating decisions through 2020.</span> Segment income (loss) from operations includes revenue less operating expenses attributable to each 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 our Ionis Core segment, we are exploiting our antisense technology to generate a broad pipeline of first-in-class and/or best-in-class medicines for us and our partners. Our Ionis Core segment generates revenue from a multifaceted partnering strategy.</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;">Akcea was</span> focused on developing and commercializing medicines to treat patients with serious and rare diseases<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. Akcea generated revenue from TEGSEDI and WAYLIVRA product sales and from its collaborations.</span></div>
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<div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">F-<span>52</span></div>
</div>
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<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;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">The following tables show our segment revenue and income (loss) from operations for </span>2020, 2019 and 2018<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> (in thousands), respectively.</span></div>
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<div><br /></div>
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  <tr>
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    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Ionis Core</div></td>
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    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Akcea Therapeutics</div></td>
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    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Elimination of</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Intercompany Activity</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Total</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; white-space: nowrap;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Revenue:</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; white-space: nowrap;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; white-space: nowrap;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; white-space: nowrap;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; white-space: nowrap;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; white-space: nowrap;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; white-space: nowrap;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; white-space: nowrap;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>
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  <tr>
    <td valign="bottom" style="vertical-align: top; width: 52%; background-color: #CCEEFF; white-space: nowrap;"><div style="text-align: left; margin-left: 25.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">SPINRAZA royalties</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_6afe8e8668b04c5fb57325d4b93bb23d" contextRef="c20200101to20201231_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_SpinrazaRoyaltiesMember_StatementBusinessSegmentsAxis_IonisCoreMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">286,583</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_4f418fb55533484c9b94b8ee10ef7898" contextRef="c20200101to20201231_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_SpinrazaRoyaltiesMember_StatementBusinessSegmentsAxis_AkceaTherapeuticsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:zerodash">&#8212;</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_e90aac00ba9f4b74bfa7df527a4402e7" contextRef="c20200101to20201231_ConsolidationItemsAxis_IntersegmentEliminationMember_ProductOrServiceAxis_SpinrazaRoyaltiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:zerodash">&#8212;</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_33b6132cd6d149bcb21f15b948504473" contextRef="c20200101to20201231_ProductOrServiceAxis_SpinrazaRoyaltiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">286,583</ix:nonFraction></div></td>
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  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: top; width: 52%; white-space: nowrap;"><div style="text-align: left; margin-left: 25.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Product sales, net</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_825dd68f3b244ab980fcb381b502335e" contextRef="c20200101to20201231_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_ProductMember_StatementBusinessSegmentsAxis_IonisCoreMember" unitRef="U001" decimals="-3" scale="3" format="ixt:zerodash">&#8212;</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_4253d66893b544a0b98945eeff82e360" contextRef="c20200101to20201231_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_ProductMember_StatementBusinessSegmentsAxis_AkceaTherapeuticsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">69,999</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_48b2d3d7430c48faa4f514df069b8308" contextRef="c20200101to20201231_ConsolidationItemsAxis_IntersegmentEliminationMember_ProductOrServiceAxis_ProductMember" unitRef="U001" decimals="-3" scale="3" format="ixt:zerodash">&#8212;</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_236e4517c52741819047698a87bd8f57" contextRef="c20200101to20201231_ProductOrServiceAxis_ProductMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">69,999</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: top; width: 52%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;"><div style="text-align: left; margin-left: 25.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Licensing and other royalty revenue</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_b9dfeeef44b447bdb8495f56c12d23ae" contextRef="c20200101to20201231_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_LicensingAndOtherRoyaltiesMember_StatementBusinessSegmentsAxis_IonisCoreMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">11,334</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_3628beb8cd0440aa9c4e2b743f6115fc" contextRef="c20200101to20201231_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_LicensingAndOtherRoyaltiesMember_StatementBusinessSegmentsAxis_AkceaTherapeuticsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:zerodash">&#8212;</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_5eeb113cac5e42f9aa002efebb601358" contextRef="c20200101to20201231_ConsolidationItemsAxis_IntersegmentEliminationMember_ProductOrServiceAxis_LicensingAndOtherRoyaltiesMember" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">3,217</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_b42c7a2cbe7c4bdeac16fe7876deace0" contextRef="c20200101to20201231_ProductOrServiceAxis_LicensingAndOtherRoyaltiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">8,117</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: top; width: 52%; padding-bottom: 2px; white-space: nowrap;"><div style="text-align: left; margin-left: 43.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total commercial revenue</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_c44a9fae3b504834badbba6952229a72" contextRef="c20200101to20201231_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_CommercialMember_StatementBusinessSegmentsAxis_IonisCoreMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">297,917</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_00ea3970f91f4a2ca51524fd6e5d8c5a" contextRef="c20200101to20201231_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_CommercialMember_StatementBusinessSegmentsAxis_AkceaTherapeuticsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">69,999</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_21b636a466964e9a96a4e4276b023022" contextRef="c20200101to20201231_ConsolidationItemsAxis_IntersegmentEliminationMember_ProductOrServiceAxis_CommercialMember" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">3,217</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_c262df0828a44f0ca600f2d34ecf59cd" contextRef="c20200101to20201231_ProductOrServiceAxis_CommercialMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">364,699</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: top; width: 52%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;"><div style="text-align: left; margin-left: 7.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">R&amp;D revenue under collaborative agreements</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_4a04a60c9cea4630a3974e9237779741" contextRef="c20200101to20201231_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_StatementBusinessSegmentsAxis_IonisCoreMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">325,024</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_c500cc672e4e4a61bdc98605f5ad035f" contextRef="c20200101to20201231_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_StatementBusinessSegmentsAxis_AkceaTherapeuticsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">82,321</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_30890e9b395041aab244b05eaa9bfc1c" contextRef="c20200101to20201231_ConsolidationItemsAxis_IntersegmentEliminationMember_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">42,780</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_49f0bd2b45984a46a61dd06f40a3a248" contextRef="c20200101to20201231_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">364,565</ix:nonFraction></div></td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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</ix:continuation></ix:continuation><ix:continuation id="Text_b381c320b41e48e6b181474f719da03e3" continuedAt="Text_b381c320b41e48e6b181474f719da03e4"><ix:continuation id="Text_a097c162b67d4481a4b05090ec96a7d011" continuedAt="Text_a097c162b67d4481a4b05090ec96a7d012">
<div><br /></div>
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<table cellpadding="0" cellspacing="0" id="zd5bde97ab66c4903be53b04e577e42d6" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
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    <td colspan="2" valign="bottom" style="vertical-align: bottom;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; white-space: nowrap;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; white-space: nowrap;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; white-space: nowrap;">&#160;</td>
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    <td colspan="2" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>
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  <tr>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
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  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: top; width: 52%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;"><div style="text-align: left; margin-left: 25.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Licensing and other royalty revenue</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_108299dc3f78432cbeda93345157c390" contextRef="c20190101to20191231_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_LicensingAndOtherRoyaltiesMember_StatementBusinessSegmentsAxis_IonisCoreMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">12,616</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_4198a0c44e4d4c119e3bba3f27762740" contextRef="c20190101to20191231_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_LicensingAndOtherRoyaltiesMember_StatementBusinessSegmentsAxis_AkceaTherapeuticsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">10,172</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_44436caf046a4b41a0411d5af56dfd9d" contextRef="c20190101to20191231_ConsolidationItemsAxis_IntersegmentEliminationMember_ProductOrServiceAxis_LicensingAndOtherRoyaltiesMember" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">5,583</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_86539ea247ab47c58125baeeffd8bf77" contextRef="c20190101to20191231_ProductOrServiceAxis_LicensingAndOtherRoyaltiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">17,205</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: top; width: 52%; padding-bottom: 2px; white-space: nowrap;"><div style="text-align: left; margin-left: 43.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total commercial revenue</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_a74b1519a21d4f6392d89d778544c1d7" contextRef="c20190101to20191231_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_CommercialMember_StatementBusinessSegmentsAxis_IonisCoreMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">305,608</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_3d84626bae4f4617b6271858829afef2" contextRef="c20190101to20191231_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_CommercialMember_StatementBusinessSegmentsAxis_AkceaTherapeuticsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">52,425</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_d09fd63c25564e329244f14aa77aa9a0" contextRef="c20190101to20191231_ConsolidationItemsAxis_IntersegmentEliminationMember_ProductOrServiceAxis_CommercialMember" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">5,583</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_389f7e0d63054fb39d19dc6da506f8e7" contextRef="c20190101to20191231_ProductOrServiceAxis_CommercialMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">352,450</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: top; width: 52%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;"><div style="text-align: left; margin-left: 7.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">R&amp;D revenue under collaborative agreements</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_8270d7f5f6c744bb92a2004a7c28da0b" contextRef="c20190101to20191231_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_StatementBusinessSegmentsAxis_IonisCoreMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">553,038</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_7e3dbc256f6c48fabac7999367080c21" contextRef="c20190101to20191231_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_StatementBusinessSegmentsAxis_AkceaTherapeuticsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">436,118</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_110d4a8b116f419b977be52cd7010d44" contextRef="c20190101to20191231_ConsolidationItemsAxis_IntersegmentEliminationMember_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">219,007</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_2904d0e875bc4fea942e1a7a98101b32" contextRef="c20190101to20191231_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">770,149</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: top; width: 52%; padding-bottom: 4px; white-space: nowrap;"><div style="text-align: left; margin-left: 25.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total segment revenue</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_4398da70003540029d0d7605e03b67dc" contextRef="c20190101to20191231_ConsolidationItemsAxis_OperatingSegmentsMember_StatementBusinessSegmentsAxis_IonisCoreMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">858,646</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_c4c389db39494e34bcc70f18ed8ca66c" contextRef="c20190101to20191231_ConsolidationItemsAxis_OperatingSegmentsMember_StatementBusinessSegmentsAxis_AkceaTherapeuticsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">488,543</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_88b7466081ca436b95e9eceb5f7eaf60" contextRef="c20190101to20191231_ConsolidationItemsAxis_IntersegmentEliminationMember" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">224,590</ix:nonFraction></div></td>
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</ix:continuation></ix:continuation><ix:continuation id="Text_b381c320b41e48e6b181474f719da03e5" continuedAt="Text_b381c320b41e48e6b181474f719da03e6"><ix:continuation id="Text_a097c162b67d4481a4b05090ec96a7d013" continuedAt="Text_a097c162b67d4481a4b05090ec96a7d014">
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>
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    <td colspan="2" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; white-space: nowrap;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; white-space: nowrap;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;"><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" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
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  </tr>
  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; white-space: nowrap;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_341d4848206f4e3cbec9234fb7359cfc" contextRef="c20180101to20181231_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_CommercialMember_StatementBusinessSegmentsAxis_AkceaTherapeuticsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">14,237</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_2d85ea774425454f8294e974309e0f99" contextRef="c20180101to20181231_ConsolidationItemsAxis_IntersegmentEliminationMember_ProductOrServiceAxis_CommercialMember" unitRef="U001" decimals="-3" scale="3" format="ixt:zerodash">&#8212;</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_d0c68b66db7b4a07a14ec99c249724a3" contextRef="c20180101to20181231_ProductOrServiceAxis_CommercialMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">254,922</ix:nonFraction></div></td>
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  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: top; width: 52%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;"><div style="text-align: left; margin-left: 7.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">R&amp;D revenue under collaborative agreements</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_df95ee27ac7f462cb96345455905d8f8" contextRef="c20180101to20181231_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_StatementBusinessSegmentsAxis_IonisCoreMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">401,259</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_472a27771e2c41b1952c38b51a763990" contextRef="c20180101to20181231_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_StatementBusinessSegmentsAxis_AkceaTherapeuticsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">50,630</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_1fa27f1eb4b54d72bb91032b29ffb598" contextRef="c20180101to20181231_ConsolidationItemsAxis_IntersegmentEliminationMember_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">107,137</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_b4ea2826218e4568bef4c392942b28dc" contextRef="c20180101to20181231_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">344,752</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: top; width: 52%; padding-bottom: 4px; white-space: nowrap;"><div style="text-align: left; margin-left: 25.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total segment revenue</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_24a4a2bacce9474ca9a3cd3ce053902e" contextRef="c20180101to20181231_ConsolidationItemsAxis_OperatingSegmentsMember_StatementBusinessSegmentsAxis_IonisCoreMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">641,944</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_f3149f9bfb8a4644bb11a55b9d5abd25" contextRef="c20180101to20181231_ConsolidationItemsAxis_OperatingSegmentsMember_StatementBusinessSegmentsAxis_AkceaTherapeuticsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">64,867</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_15cdc207e58b4f26bc58ff17b1e5c225" contextRef="c20180101to20181231_ConsolidationItemsAxis_IntersegmentEliminationMember" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">107,137</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_537a36a3fb2c4240830bf14f1fc0e530" contextRef="c20180101to20181231" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">599,674</ix:nonFraction></div></td>
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  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: top; width: 52%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;"><div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total operating expenses</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:CostsAndExpenses" id="Fact_1b8dc8f1f1354498ac3cb49477328548" contextRef="c20180101to20181231_ConsolidationItemsAxis_OperatingSegmentsMember_StatementBusinessSegmentsAxis_IonisCoreMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">380,212</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:CostsAndExpenses" id="Fact_eeb2dc8a1acc47b3bee47d336d5e9f2b" contextRef="c20180101to20181231_ConsolidationItemsAxis_OperatingSegmentsMember_StatementBusinessSegmentsAxis_AkceaTherapeuticsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">295,683</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:CostsAndExpenses" id="Fact_25a14b8a961e4d22b16608d8fbd24489" contextRef="c20180101to20181231_ConsolidationItemsAxis_IntersegmentEliminationMember" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">14,849</ix:nonFraction></div></td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#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;">The following table shows our total assets by segment at December 31, 2020 and 2019 (in thousands), respectively.</div>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Ionis Core</div></td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Akcea Therapeutics</div></td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Elimination of</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Intercompany Activity</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Total</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: top; width: 52%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;"><div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">December 31, 2020</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:Assets" id="Fact_e878b5b1327943bf9fe8329a61b7ca25" contextRef="c20201231_ConsolidationItemsAxis_IntersegmentEliminationMember" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">838,291</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:Assets" id="Fact_bd3cd73399c64f20b57693c66dc37ab9" contextRef="c20201231" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">2,389,755</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: top; width: 52%; padding-bottom: 4px; white-space: nowrap;"><div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">December 31, 2019</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:Assets" id="Fact_165a2783f8ad4636aa05337476ec6f11" contextRef="c20191231_ConsolidationItemsAxis_OperatingSegmentsMember_StatementBusinessSegmentsAxis_IonisCoreMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">3,478,081</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:Assets" id="Fact_0c0f2ea58e66476ea656ccf108f71566" contextRef="c20191231_ConsolidationItemsAxis_OperatingSegmentsMember_StatementBusinessSegmentsAxis_AkceaTherapeuticsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">599,250</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:Assets" id="Fact_474f897008694a98a304e7242c4bd91b" contextRef="c20191231_ConsolidationItemsAxis_IntersegmentEliminationMember" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">844,219</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:Assets" id="Fact_72af7c7066294da4883e92aa73bfecde" contextRef="c20191231" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">3,233,112</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>
  </tr>
</table>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Contracts receivables at December 31, 2020 was comprised of approximately <ix:nonFraction name="us-gaap:ConcentrationRiskPercentage1" id="Fact_28f0adbb41bc491dba19be13a5d7e43d" contextRef="c20200101to20201231_ConcentrationRiskByBenchmarkAxis_AccountsReceivableMember_ConcentrationRiskByTypeAxis_CreditConcentrationRiskMember_MajorCustomersAxis_SignificantPartnersMember" unitRef="U003" decimals="3" scale="-2" format="ixt:numdotdecimal">99.5</ix:nonFraction>percent from <ix:nonFraction name="ions:NumberOfSignificantPartners" id="Fact_f77b5cfe2f944a15983b965d2dedff4b" contextRef="c20200101to20201231" unitRef="U018" decimals="INF" scale="0" format="ixt-sec:numwordsen">two</ix:nonFraction> significant partners. Contracts receivables at December 31, 2019 was comprised of approximately <ix:nonFraction name="us-gaap:ConcentrationRiskPercentage1" id="Fact_c4c378b8ae064fe395c207087887b3e5" contextRef="c20190101to20191231_ConcentrationRiskByBenchmarkAxis_AccountsReceivableMember_ConcentrationRiskByTypeAxis_CreditConcentrationRiskMember_MajorCustomersAxis_SignificantPartnersMember" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">75</ix:nonFraction> percent from <ix:nonFraction name="ions:NumberOfSignificantPartners" id="Fact_4c28cf57e67b421f9e33d6b9fe701b2c" contextRef="c20190101to20191231" unitRef="U018" decimals="INF" scale="0" format="ixt-sec:numwordsen">one</ix:nonFraction> significant partner.</div>
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<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">F-<span>53</span></div>
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<div><ix:nonNumeric name="us-gaap:PensionAndOtherPostretirementBenefitsDisclosureTextBlock" id="Text_44a1974bfba9485682c02d2913778f03" contextRef="c20200101to20201231" escape="true" continuedAt="Text_6eff2267db1d40a1ab2241e759443f1e1">
<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">10. Employment Benefits</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We have employee 401(k) salary deferral plans covering all employees. Employees could make contributions by withholding a percentage of their salary up to the IRS annual limits of $<ix:nonFraction name="us-gaap:DefinedContributionPlanMaximumAnnualContributionsPerEmployeeAmount" id="Fact_06c142c7ec1040e0b05c4b2596dfe112" contextRef="c20200101to20201231_RangeAxis_MinimumMember" unitRef="U001" decimals="0" scale="0" format="ixt:numdotdecimal">19,500</ix:nonFraction> and $<ix:nonFraction name="us-gaap:DefinedContributionPlanMaximumAnnualContributionsPerEmployeeAmount" id="Fact_2703ad6213db4e249c38d0794a2c6418" contextRef="c20200101to20201231_RangeAxis_MaximumMember" unitRef="U001" decimals="0" scale="0" format="ixt:numdotdecimal">26,000</ix:nonFraction> in 2020 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="c20200101to20201231" unitRef="U001" decimals="-5" scale="6" format="ixt:numdotdecimal">5.7</ix:nonFraction> million, $<ix:nonFraction name="us-gaap:DefinedContributionPlanCostRecognized" id="Fact_47a2898dc66b4221ba3a2d92c2c0643a" contextRef="c20190101to20191231" unitRef="U001" decimals="-5" scale="6" format="ixt:numdotdecimal">6.4</ix:nonFraction> million and $<ix:nonFraction name="us-gaap:DefinedContributionPlanCostRecognized" id="Fact_0c0b367e1550466b886c0390a13e1e0f" contextRef="c20180101to20181231" unitRef="U001" decimals="-5" scale="6" format="ixt:numdotdecimal">5.7</ix:nonFraction> million in matching contributions for the years ended December 31, 2020, 2019 and 2018, respectively.</div>
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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>
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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 the potential loss from any legal proceeding is considered probable and the amount can be reasonably estimated, we accrue a liability for the estimated loss. Significant judgment is required to determine the probability of a loss and whether the amount of the loss is reasonably estimable. The outcome of any proceeding is not determinable in advance. As a result, the assessment of a potential liability and the amount of accruals recorded are based only on the information available to us at the time. As additional information becomes available, we reassess the potential liability related to the legal proceeding, and may revise our estimates.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">On July 16, 2020, a purported stockholder of Akcea filed an action in the Delaware Court of Chancery captioned John Makris, et al. v. Stanley T. Crooke, et al., C.A. No. 2020-0587, or the &#8220;Delaware Action.&#8221; The plaintiff in the Delaware Action asserts claims against (i) current and former members of Akcea&#8217;s board of directors; and (ii) Ionis, or collectively, the &#8220;Defendants&#8221;. The plaintiff asserts derivative claims on behalf of Akcea, which is a nominal defendant in the Delaware Action, as well as putatively direct claims on behalf of a purported class of Akcea&#8217;s stockholders. The plaintiff in the Delaware action asserts that the Defendants breached their fiduciary duties in connection with the licensing transaction that we and Akcea entered into regarding TEGSEDI and IONIS-TTR-L</span><sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. The plaintiff also asserts an unjust enrichment claim against Ionis. The plaintiff&#8217;s claims are similar to those asserted in a prior action in the Delaware Court of Chancery captioned City of Cambridge Retirement System v. Crooke, et al., C.A. No. 2019-0905, which was dismissed with prejudice to the named plaintiff only on April 8, 2020. We believe that the claims asserted in the Delaware Action are without merit and anticipate filing a motion to dismiss the claims.</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;">In light of the August 31, 2020 public announcement of the Akcea Acquisition, the parties to the Delaware Action entered into a stipulation whereby the Defendants need to respond to the complaint filed on July 16, 2020, and the plaintiff will file an amended complaint. The amended complaint has not yet been filed.</span></div>
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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>
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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 for a fair statement of the results of the interim periods. Summarized fourth quarter data for 2020 and 2019 are as follows (in thousands, except per share data).</div>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#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;">Diluted net income (loss) per share (1) (3)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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</ix:continuation></ix:continuation><ix:continuation id="Text_41b76e849bc84751a7cebc0d01f58d273" continuedAt="Text_41b76e849bc84751a7cebc0d01f58d274"><ix:continuation id="Text_eabfc667a57c4a12852f398ec6e373505" continuedAt="Text_eabfc667a57c4a12852f398ec6e373506">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">________________</div>
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<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="z95fc0fe83dcc44d3beffd99343c41418">
  <tr>
    <td style="width: 36pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(1)</td>
    <td style="width: auto; vertical-align: top; text-align: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><ix:footnote id="Foot_260ceacf638c4b6691c7c678cfe81725" footnoteRole="http://www.xbrl.org/2003/role/footnote" xml:lang="en-US" continuedAt="Foot_7a0fd283e3af49e49d6d00f38676999a1">We </ix:footnote></span><ix:continuation id="Foot_7a0fd283e3af49e49d6d00f38676999a1" continuedAt="Foot_7a0fd283e3af49e49d6d00f38676999a2">compute net income (loss) per share independently for each quarter during </ix:continuation><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><ix:continuation id="Foot_7a0fd283e3af49e49d6d00f38676999a2">the year.</ix:continuation></span></div></td>
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</table>
</ix:continuation></ix:continuation><ix:continuation id="Text_41b76e849bc84751a7cebc0d01f58d275" continuedAt="Text_41b76e849bc84751a7cebc0d01f58d276"><ix:continuation id="Text_eabfc667a57c4a12852f398ec6e373507" continuedAt="Text_eabfc667a57c4a12852f398ec6e373508">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_41b76e849bc84751a7cebc0d01f58d276" continuedAt="Text_41b76e849bc84751a7cebc0d01f58d277"><ix:continuation id="Text_eabfc667a57c4a12852f398ec6e373508" continuedAt="Text_eabfc667a57c4a12852f398ec6e373509">
<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="z7f159b28bab545f4b7ef06cc58aafa2d">
  <tr>
    <td style="width: 36pt; vertical-align: top; align: right; 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" continuedAt="Foot_fe22222ae8254d4da148f4f08329b9cc1">As discussed in Note 1, </ix:footnote><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"><ix:continuation id="Foot_fe22222ae8254d4da148f4f08329b9cc1" continuedAt="Foot_fe22222ae8254d4da148f4f08329b9cc2">Organization and Significant Accounting Policies, </ix:continuation></span><ix:continuation id="Foot_fe22222ae8254d4da148f4f08329b9cc2">we compute basic net income (loss) per share by dividing the total net income (loss) attributable to our common stockholders by our weighted-average number of common shares outstanding during the period. Our basic net income (loss) per share calculation for each of the fourth quarters in 2020 and 2019 considered our net income (loss) for Ionis on a stand-alone basis plus our share of Akcea&#8217;s net loss for the period. To calculate the portion of Akcea&#8217;s net loss attributable to our ownership, we multiplied Akcea&#8217;s loss per share by the weighted average shares we owned in Akcea during the period. As a result of this calculation, our total net income (loss) available to Ionis common stockholders for the calculation of net income (loss) per share is different than net income (loss) attributable to Ionis Pharmaceuticals, Inc. common stockholders in the consolidated statements of operations.</ix:continuation></div></td>
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<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">F-<span>54</span></div>
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<div><ix:continuation id="Text_41b76e849bc84751a7cebc0d01f58d277" continuedAt="Text_41b76e849bc84751a7cebc0d01f58d278"><ix:continuation id="Text_eabfc667a57c4a12852f398ec6e373509" continuedAt="Text_eabfc667a57c4a12852f398ec6e3735010">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_41b76e849bc84751a7cebc0d01f58d278" continuedAt="Text_41b76e849bc84751a7cebc0d01f58d279"><ix:continuation id="Text_eabfc667a57c4a12852f398ec6e3735010" continuedAt="Text_eabfc667a57c4a12852f398ec6e3735011">
<div style="text-align: justify; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our basic net income (loss) per share the quarter referenced was calculated as follows (in thousands, except per share amounts):</div>
</ix:continuation></ix:continuation><ix:continuation id="Text_41b76e849bc84751a7cebc0d01f58d279" continuedAt="Text_41b76e849bc84751a7cebc0d01f58d2710"><ix:continuation id="Text_eabfc667a57c4a12852f398ec6e3735011" continuedAt="Text_eabfc667a57c4a12852f398ec6e3735012">
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</ix:continuation></ix:continuation><ix:continuation id="Text_41b76e849bc84751a7cebc0d01f58d2710" continuedAt="Text_41b76e849bc84751a7cebc0d01f58d2711"><ix:continuation id="Text_eabfc667a57c4a12852f398ec6e3735012" continuedAt="Text_eabfc667a57c4a12852f398ec6e3735013">
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Basic Net Loss</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Per Share</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Calculation</div></td>
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  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;"><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: top; width: 64%; padding-bottom: 2px; white-space: nowrap;"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Akcea&#8217;s net loss in the post-acquisition period attributable to our ownership</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:NetIncomeLoss" id="Fact_73380a129f40470fbe4d5f0d43e465bf" contextRef="c20201101to20201231_OwnershipAxis_AkceaTherapeuticsIncMember" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">85,987</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: top; width: 64%; background-color: #CCEEFF; white-space: nowrap;"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Akcea&#8217;s total net loss attributable to our ownership</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: top; width: 64%; padding-bottom: 2px; white-space: nowrap;"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Ionis&#8217; stand-alone net loss</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; white-space: nowrap;">&#160;</td>
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  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net loss available to Ionis common stockholders</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
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<div><br /></div>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
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  <tr>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;">&#160;</td>
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  <tr>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:IncrementalCommonSharesAttributableToConversionOfDebtSecurities" id="Fact_5d17c5fb8b174b72ad0d75f02355d8fd" contextRef="c20191001to20191231_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">9,527</ix:nonFraction></div></td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>
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<DOCUMENT>
<TYPE>EX-10.18
<SEQUENCE>2
<FILENAME>exhibit10_18.htm
<DESCRIPTION>EXHIBIT 10.18
<TEXT>
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      <div style="text-align: right; font-weight: bold;">EXHIBIT 10.18</div>
      <div style="font-variant: small-caps; text-align: center;"> <br>
      </div>
      <div style="font-variant: small-caps; text-align: center; font-weight: bold;">IONIS PHARMACEUTICALS, INC.<br>
      </div>
      <div style="font-variant: small-caps; text-align: center;"><font style="font-weight: bold;">PERFORMANCE BASED RESTRICTED STOCK UNIT GRANT NOTICE</font><font style="font-weight: bold;"><br>
        </font></div>
      <div style="font-variant: small-caps; text-align: center;"><font style="font-weight: bold;">(2011 EQUITY INCENTIVE PLAN)</font><br>
      </div>
      <br>
      <div>Ionis Pharmaceuticals, Inc. (the <font style="font-weight: bold; font-style: italic;">&#8220;Company&#8221;</font>), pursuant to its Amended and Restated 2011 Equity Incentive Plan (the <font style="font-weight: bold; font-style: italic;">&#8220;Plan&#8221;</font>),
        hereby awards to Participant a Performance Based Restricted Stock Unit (<font style="font-weight: bold; font-style: italic;">&#8220;PRSU&#8221;</font>) Award for the number of stock units set forth below (the <font style="font-weight: bold; font-style: italic;">&#8220;Award&#8221;</font>).&#160; The Award is subject to all of the terms and conditions as set forth herein; and in the Plan and the Performance Based Restricted Stock Unit Agreement (the <font style="font-weight: bold; font-style: italic;">&#8220;Agreement&#8221;</font>),

        both of which are attached hereto and incorporated herein in their entirety.&#160; Capitalized terms not otherwise defined herein shall have the meanings set forth in the Plan or the Agreement.&#160; In the event of any conflict between the terms in the
        Award and the Plan, the terms of the Plan shall control.</div>
      <div>&#160;</div>
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          <tr>
            <td style="width: 32%; vertical-align: top; padding-bottom: 2px;">
              <div style="text-align: justify;">Participant:</div>
            </td>
            <td style="width: 38%; vertical-align: top; border-bottom: 2px solid rgb(0, 0, 0);">&#160;</td>
          </tr>
          <tr>
            <td style="width: 32%; vertical-align: top; padding-bottom: 2px;">
              <div style="text-align: justify;">Date of Grant:</div>
            </td>
            <td style="width: 38%; vertical-align: top; border-bottom: 2px solid rgb(0, 0, 0);">&#160;</td>
          </tr>
          <tr>
            <td style="width: 32%; vertical-align: top; padding-bottom: 2px;">
              <div style="text-align: justify;">Target Number of Stock Units Subject to Award:</div>
            </td>
            <td style="width: 38%; vertical-align: top; border-bottom: 2px solid rgb(0, 0, 0);">&#160;</td>
          </tr>
          <tr>
            <td style="width: 32%; vertical-align: top; padding-bottom: 2px;">
              <div style="text-align: justify;">Maximum Number of Stock Units Subject to Award:</div>
            </td>
            <td style="width: 38%; vertical-align: top; border-bottom: 2px solid rgb(0, 0, 0);">&#160;</td>
          </tr>
          <tr>
            <td style="width: 32%; vertical-align: top;">
              <div style="text-align: justify;">Consideration:</div>
            </td>
            <td style="width: 38%; vertical-align: top;">
              <div style="text-align: justify;">Participant&#8217;s Services</div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
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          <tr>
            <td style="width: 89.1pt; vertical-align: top;"><font style="font-weight: bold;">Vesting Schedule</font>:</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>Subject to Section 4(b) of the Agreement, if Participant ceases to be a Service Provider for any or no reason before Participant vests in the PRSU, the PRSU and Participant&#8217;s right to acquire any Shares hereunder will immediately
                terminate.</div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <div style="text-align: justify; margin-left: 90pt;">Up to one third (1/3) of the maximum number of PRSUs subject to the Agreement are eligible for vesting at the end of each Performance Period depending on the Company&#8217;s relative Total Shareholder
        Return over the applicable Performance Periods, but subject to the Alternative Three Year Performance Period Vested Unit Calculation (each as more fully described in the PRSU Agreement).</div>
      <div><br>
      </div>
      <div style="text-align: justify; margin-left: 90pt;">You must accept this Award prior to the first vesting date. If you do not accept this Award by the first vest date, this Award will automatically expire.</div>
      <div><br>
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          <tr>
            <td style="width: 90pt; vertical-align: top; font-weight: bold;">Issuance Schedule:</td>
            <td style="vertical-align: top; text-align: justify;">
              <div>The shares of Common Stock to be issued in respect of the Award will be issued in accordance with Section 1 of the Agreement.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
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          <tr>
            <td style="width: 90pt; vertical-align: top; font-weight: bold;">
              <div>Special Tax</div>
              <div>Withholding Right:</div>
            </td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-style: italic;">If permitted by the Company</font>,<font style="font-weight: bold;">&#160;</font>you may direct the Company (i) to withhold, from shares otherwise issuable in respect of the Award, a portion of those shares
                with an aggregate fair market value (measured as of the delivery date) equal to the amount of the applicable withholding taxes, and (ii) to make a cash payment equal to such fair market value directly to the appropriate taxing authorities,
                as provided in Section 12 of the Agreement.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <div style="text-align: justify;"><font style="font-weight: bold;">Additional Terms/Acknowledgements:</font>&#160; The undersigned Participant acknowledges receipt of, and understands and agrees to, this Grant Notice, the Agreement and the Plan.&#160;
        Participant further acknowledges that as of the Date of Grant, this Grant Notice, the Agreement and the Plan set forth the entire understanding between Participant and the Company regarding the Award and supersede all prior oral and written
        agreements on that subject, with the exception of any employment or severance arrangement that would provide for vesting acceleration of the Award upon the terms and conditions set forth therein.</div>
      <div>&#160;</div>
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          <tr>
            <td style="vertical-align: top;" colspan="2">
              <div style="text-align: justify; font-variant: small-caps; font-weight: bold;">Ionis Pharmaceuticals, Inc.</div>
            </td>
            <td style="vertical-align: top; width: 10%;" colspan="1">&#160;</td>
            <td style="vertical-align: top; width: 45%;">
              <div style="text-align: justify; font-variant: small-caps; font-weight: bold;">Participant:</div>
            </td>
          </tr>
          <tr>
            <td style="vertical-align: top;" colspan="2">&#160;</td>
            <td style="vertical-align: top; width: 10%;" colspan="1">&#160;</td>
            <td style="vertical-align: top; width: 45%;">&#160;</td>
          </tr>
          <tr>
            <td style="width: 3%; vertical-align: top; padding-bottom: 2px;">
              <div style="text-align: justify;">By:</div>
            </td>
            <td style="width: 42%; vertical-align: top; border-bottom: 2px solid rgb(0, 0, 0);">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; <br>
            </td>
            <td style="vertical-align: top; padding-bottom: 2px; width: 10%;" colspan="1">&#160;</td>
            <td style="vertical-align: top; border-bottom: 2px solid rgb(0, 0, 0); width: 45%;">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; <br>
            </td>
          </tr>
          <tr>
            <td style="vertical-align: top;" colspan="2">
              <div style="text-align: center;">Signature</div>
            </td>
            <td style="vertical-align: top; width: 10%;" colspan="1">&#160;</td>
            <td style="vertical-align: top; width: 45%;">
              <div style="text-align: center;">Signature</div>
            </td>
          </tr>
          <tr>
            <td style="vertical-align: top;" rowspan="1" colspan="2">&#160;&#160;</td>
            <td style="vertical-align: top; width: 10%;" rowspan="1" colspan="1">&#160;</td>
            <td style="width: 45%; vertical-align: top;" rowspan="1">&#160;&#160;</td>
          </tr>

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          <tr>
            <td style="width: 5%; vertical-align: top; padding-bottom: 2px;">
              <div style="text-align: justify;">Title:</div>
            </td>
            <td style="width: 40%; vertical-align: top; border-bottom: 2px solid rgb(0, 0, 0);">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </td>
            <td style="vertical-align: top; padding-bottom: 2px; width: 10%;" colspan="1">&#160;</td>
            <td style="width: 5%; vertical-align: top; padding-bottom: 2px;">
              <div style="text-align: justify;">Date:</div>
            </td>
            <td style="width: 40%; vertical-align: top; border-bottom: 2px solid rgb(0, 0, 0);">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </td>
          </tr>
          <tr>
            <td style="width: 5%; vertical-align: top;" rowspan="1">&#160;</td>
            <td style="width: 40%; vertical-align: top;" rowspan="1">&#160;</td>
            <td style="vertical-align: top; width: 10%;" colspan="1" rowspan="1">&#160;</td>
            <td style="vertical-align: top;" colspan="2" rowspan="1">&#160;</td>
          </tr>
          <tr>
            <td style="width: 5%; vertical-align: top; padding-bottom: 2px;">
              <div style="text-align: justify;">Date:</div>
            </td>
            <td style="width: 40%; vertical-align: top; border-bottom: 2px solid rgb(0, 0, 0);">&#160;</td>
            <td style="vertical-align: top; width: 10%; padding-bottom: 2px;" colspan="1">&#160;</td>
            <td style="vertical-align: top; padding-bottom: 2px;" colspan="2">&#160;</td>
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          <tr>
            <td style="width: 90pt; vertical-align: top;"><font style="font-weight: bold; font-variant: small-caps;">Attachments</font>:</td>
            <td style="width: auto; vertical-align: top;">
              <div>Performance Based Restricted Stock Unit Agreement</div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <div id="DSPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
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          <hr style="margin: 4px 0px; width: 100%; border-width: 0px; height: 2px; color: rgb(0, 0, 0); background-color: rgb(0, 0, 0); clear: both;" noshade="noshade"></div>
      </div>
      <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;">AMENDED <font style="font-variant: normal;">&amp; RESTATED 2011 EQUITY INCENTIVE PLAN<br>
        </font></div>
      <div style="text-align: center; font-variant: small-caps; font-weight: bold;"><font style="font-variant: normal;"> <br>
        </font></div>
      <div style="text-align: center; font-variant: normal; font-weight: bold;">PERFORMANCE BASED RESTRICTED STOCK UNIT AGREEMENT</div>
      <div>&#160;</div>
      <div style="text-align: justify; text-indent: 36pt;">Pursuant to the Performance Based Restricted Stock Unit Grant Notice (&#8220;<font style="font-weight: bold; font-style: italic;">Grant Notice</font>&#8221;) and this Performance Based Restricted Stock Unit
        Agreement (&#8220;<font style="font-weight: bold; font-style: italic;">Agreement</font>&#8221;) and in consideration of your services, Ionis Pharmaceuticals, Inc. (the &#8220;<font style="font-weight: bold; font-style: italic;">Company</font>&#8221;) has awarded you a
        Performance Based Restricted Stock Unit Award (the &#8220;<font style="font-weight: bold; font-style: italic;">Award</font>&#8221;) under its Amended &amp; Restated 2011 Equity Incentive Plan (the &#8220;<font style="font-weight: bold; font-style: italic;">Plan</font>&#8221;).

        Your Award is granted to you effective as of the Date of Grant set forth in the Grant Notice for this Award.&#160; This Agreement will be deemed to be agreed to by the Company and you upon the earlier of (i) signing (or electronic acceptance) by you of
        the Grant Notice to which it is attached, and (ii) your receipt of shares of Common Stock under this Agreement.&#160; Capitalized terms not explicitly defined in this Agreement will have the same meanings given to them in the Plan or the Grant Notice,
        as applicable.&#160; In the event of any conflict between the terms in this Agreement and the Plan, the terms of the Plan will control.&#160; The details of your Award, in addition to those set forth in the Grant Notice and the Plan, are as follows.</div>
      <div>&#160;</div>
      <div>
        <div style="font-variant: small-caps; font-weight: bold; margin-left: 36pt;">1.&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; <font style="text-transform: uppercase;">Grant And Vesting of the Award.</font></div>
      </div>
      <div>&#160;</div>
      <div style="text-align: justify; text-indent: 72pt;"><font style="font-weight: bold; color: rgb(0, 0, 0);">(a)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;This Award represents the right to be issued on a future date the number of shares of the Company&#8217;s Common Stock that is
        equal to the number of performance based restricted stock units (&#8220;<font style="font-weight: bold; font-style: italic;">PRSUs</font>&#8221;) as described below. This Award was granted in consideration of your services to the Company.&#160; Except as otherwise
        provided herein, you will not be required to make any payment to the Company (other than past and future services to the Company) with respect to your receipt of the Award, the vesting of the PRSUs or the delivery of the Common Stock to be issued
        in respect of the Award.</div>
      <div>&#160;</div>
      <div style="text-align: justify; text-indent: 72pt;"><font style="font-weight: bold; color: rgb(0, 0, 0);">(b)</font>&#160;&#160;&#160;&#160;&#160;&#160; One third (1/3) of the maximum number of PRSUs subject to this Agreement are eligible for vesting at the end of each
        Performance Period depending on the Company&#8217;s relative Total Shareholder Return over the applicable Performance Period, but <font style="font-style: italic;">subject to</font> the Alternative Three Year Performance Period Vested Unit Calculation
        (each as more fully described below).</div>
      <div>&#160;</div>
      <div style="text-align: justify; text-indent: 72pt;"><font style="font-weight: bold;">(c)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; Following the end of each Performance Period, the Company&#8217;s Compensation Committee (the &#8220;<font style="font-weight: bold; font-style: italic;">Committee</font>&#8221;)

        will certify the Company&#8217;s relative Total Shareholder Return on a percentage rank basis compared to the Comparison Group (the &#8220;<font style="font-weight: bold; font-style: italic;">Performance Measure</font>&#8221;) for such Performance Period (the &#8220;<font style="font-weight: bold; font-style: italic;">Certification</font>&#8221;). The PRSUs subject to vesting during a Performance Period will be subject to forfeiture and cancellation by the Company if the Company&#8217;s performance during such Performance
        Period does not meet or exceed the Threshold Level (as defined in the table set forth in Section 3(a)(iii)) of the Performance Measure for such Performance Period; <font style="font-style: italic;">provided however</font>, that such forfeited
        shares may be subsequently granted subject to the Alternative Three Year Performance Period Vested Unit Calculation. Performance at or above the Threshold Level will result in PRSUs becoming vested as set forth below, and shares underlying such
        vested PRSUs will be promptly distributed following completion of the Certification but in no event later than March 15 of the year following the year in which the applicable Certification occurred.</div>
      <div>&#160;</div>
      <div id="DSPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
        <div id="DSPFPageBreak" style="page-break-after: always;">
          <hr style="margin: 4px 0px; width: 100%; border-width: 0px; height: 2px; color: rgb(0, 0, 0); background-color: rgb(0, 0, 0); clear: both;" noshade="noshade"></div>
      </div>
      <div style="text-align: justify; text-indent: 72pt;"><font style="font-weight: bold;">(d)</font>&#160;&#160;&#160;&#160;&#160; &#160;&#160; Notwithstanding the foregoing, following completion of the three-year period commencing on the Date of Grant and ending on the third anniversary
        of the Date of Grant (the &#8220;<font style="font-weight: bold; font-style: italic;">Three Year Performance Period</font>&#8221;), the Committee will determine the number of PRSUs that would vest if the maximum number of PRSUs subject to the Award had been
        subject only to the Three Year Performance Period (the &#8220;<font style="font-weight: bold; font-style: italic;">Alternative Three Year Performance Period Vested Unit Calculation</font>&#8221;). If the number of PRSUs that vest pursuant to the Alternative
        Three Year Performance Period Vested Unit Calculation is greater than the number of PRSUs that vest under this Agreement in the three Performance Periods described herein without regard to the Alternative Three Year Performance Period Vested Unit
        Calculation, then such greater number of PRSUs will vest pursuant to the Alternative Three Year Performance Period Vested Unit Calculation, reduced by the number of PRSUs previously vested.</div>
      <div>&#160;</div>
      <div style="text-align: justify; text-indent: 36pt;"><font style="font-weight: bold; color: rgb(0, 0, 0);">2.</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; &#160; <font style="text-transform: uppercase;"><font style="font-weight: bold; font-variant: small-caps;">Additional Definitions</font>.</font></div>
      <div>&#160;</div>
      <div style="text-align: justify; text-indent: 72pt;"><font style="font-weight: bold; color: rgb(0, 0, 0);">(a)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#8220;<font style="font-weight: bold; font-style: italic;">Comparison Group</font>&#8221; means the companies included in the NASDAQ
        Biotechnology Index on the Date of Grant, as may be adjusted as described in Section 3(b)(iii) below.</div>
      <div>&#160;</div>
      <div style="text-align: justify; text-indent: 72pt;"><font style="font-weight: bold; color: rgb(0, 0, 0);">(b)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#8220;<font style="font-weight: bold; font-style: italic;">Performance Period</font>&#8221; means each of the following three periods:</div>
      <div>&#160;</div>
      <div style="text-align: justify; text-indent: 108pt;"><font style="font-weight: bold; color: rgb(0, 0, 0);">&#160;(i)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; the one-year period commencing on the Date of Grant and ending on the first anniversary of the Date of Grant;</div>
      <div>&#160;</div>
      <div style="text-align: justify; text-indent: 108pt;"><font style="font-weight: bold; color: rgb(0, 0, 0);">&#160;(ii)</font>&#160;&#160;&#160;&#160;&#160; &#160; the two-year period commencing on the Date of Grant and ending on the second anniversary of the Date of Grant; and</div>
      <div>&#160;</div>
      <div style="text-align: justify; text-indent: 108pt;"><font style="font-weight: bold; color: rgb(0, 0, 0);">&#160;(iii)</font>&#160;&#160;&#160;&#160;&#160;&#160; the three-year period commencing <a name="z_Hlk29813503"></a>on the Date of Grant and ending on the third anniversary of
        the Date of Grant.</div>
      <div style="text-align: justify; text-indent: 108pt;"> <br>
      </div>
      <div style="text-align: justify; text-indent: 72pt;"><font style="font-weight: bold; color: rgb(0, 0, 0);">(c)</font>&#160;&#160;&#160;&#160;&#160; &#160; &#160;&#160; &#8220;<font style="font-weight: bold; font-style: italic;">Target</font>&#8221; means the target number of shares set forth in the
        Grant Notice.&#160; The Target for each Performance Period will be one-third of the target number of shares set forth in the Grant Notice.</div>
      <div>&#160;</div>
      <div style="text-align: justify; text-indent: 72pt;"><font style="font-weight: bold; color: rgb(0, 0, 0);">(d)</font>&#160;&#160;&#160;&#160;&#160;&#160; &#8220;<font style="font-weight: bold; font-style: italic;">Total Shareholder Return</font>&#8221; or &#8220;<font style="font-weight: bold; font-style: italic;">TSR</font>&#8221; means total shareholder return as applied to the Company or any company in the Comparison Group, meaning stock price appreciation from the beginning to the end of the applicable Performance Period, plus dividends
        and distributions made or declared (assuming such dividends or distributions are reinvested in the common stock of the Company or any company in the Comparison Group) during the Performance Period, expressed as a percentage return.</div>
      <div>&#160;</div>
      <div style="text-align: justify; text-indent: 36pt;"><font style="font-weight: bold; color: rgb(0, 0, 0);">3.</font>&#160;&#160;&#160;&#160;&#160;&#160; &#160;&#160; &#160; <font style="text-transform: uppercase;"><font style="font-weight: bold; font-variant: small-caps;">Calculation</font>.</font></div>
      <div>&#160;</div>
      <div style="text-align: justify; text-indent: 72pt;"><font style="font-weight: bold; color: rgb(0, 0, 0);">(a)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160; &#160; For purposes of the Award, subject to the Negative TSR Cap set forth in Section 3(b)(i) below, the number of PRSUs earned
        at the end of each Performance Period will be calculated using the method as follows:</div>
      <div>&#160;</div>
      <div id="DSPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
        <div id="DSPFPageBreak" style="page-break-after: always;">
          <hr style="margin: 4px 0px; width: 100%; border-width: 0px; height: 2px; color: rgb(0, 0, 0); background-color: rgb(0, 0, 0); clear: both;" noshade="noshade"></div>
      </div>
      <div style="text-align: justify; text-indent: 108pt;"><font style="font-weight: bold; color: rgb(0, 0, 0);">&#160;(i)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160; First, for the Company and for each other company in the Comparison Group, determine the TSR for the Performance Period.</div>
      <div>&#160;</div>
      <div style="text-align: justify; text-indent: 108pt;"><font style="font-weight: bold; color: rgb(0, 0, 0);">&#160;(ii)</font>&#160;&#160;&#160;&#160;&#160;&#160; Next, rank the TSR values determined in step (i) above from low to high (with the company having the lowest TSR being
        ranked number 1, the company with the second lowest TSR ranked number 2, and so on) and determine the Company&#8217;s percentile rank based upon its position in the list by dividing the Company&#8217;s position by the total number of companies (including the
        Company) in the Comparison Group and rounding the quotient to the nearest hundredth. For example, if the Company was ranked 60 on the list out of 80 companies (including the Company), its percentile rank would be 75%.</div>
      <div>&#160;</div>
      <div style="text-align: justify; text-indent: 108pt;"><font style="font-weight: bold; color: rgb(0, 0, 0);">&#160;(iii)</font>&#160;&#160;&#160;&#160;&#160;&#160; Finally, plot the percentile rank for the Company determined in accordance with step (ii) above into the appropriate band
        in the left-hand column of the table below to determine the number of shares earned as a percent of the applicable Target for the applicable Performance Period, which is the figure in the right-hand column of the table below corresponding to that
        percentile rank. Use linear interpolation between points in the table below to determine the percentile rank and the corresponding share funding if the Company&#8217;s percentile rank is greater than 25% and less than 75% but not exactly one of the
        percentile ranks listed in the left-hand column.</div>
      <div>&#160;</div>
      <div style="margin-left: 36pt;">
        <table id="zf409e8224af344ee9d57f26d858d06d2" style="border-collapse: collapse; width: 60%; color: #000000; font-family: 'Times New Roman'; font-size: 10pt; text-align: left;" border="0" cellpadding="0" cellspacing="0">

            <tr>
              <td style="width: 20%; vertical-align: top;">&#160;</td>
              <td style="width: 20%; vertical-align: bottom;">
                <div style="text-align: center; font-weight: bold;"><u>TSR Percentile Rank</u></div>
              </td>
              <td style="width: 20%; vertical-align: top;">
                <div style="text-align: center; font-weight: bold;"><u>Shares Earned as a</u></div>
                <div style="text-align: center; font-weight: bold;"><u>Percent of Target</u></div>
              </td>
            </tr>
            <tr>
              <td style="width: 20%; vertical-align: top; background-color: rgb(204, 238, 255);">
                <div style="text-align: justify; font-weight: bold;">Maximum Level</div>
              </td>
              <td style="width: 20%; vertical-align: top; background-color: rgb(204, 238, 255);">
                <div style="text-align: center;">75%</div>
              </td>
              <td style="width: 20%; vertical-align: top; background-color: rgb(204, 238, 255);">
                <div style="text-align: center;">150%</div>
              </td>
            </tr>
            <tr>
              <td style="width: 20%; vertical-align: top;">&#160;</td>
              <td style="width: 20%; vertical-align: top;">
                <div style="text-align: center;">70%</div>
              </td>
              <td style="width: 20%; vertical-align: top;">
                <div style="text-align: center;">140%</div>
              </td>
            </tr>
            <tr>
              <td style="width: 20%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
              <td style="width: 20%; vertical-align: top; background-color: rgb(204, 238, 255);">
                <div style="text-align: center;">65%</div>
              </td>
              <td style="width: 20%; vertical-align: top; background-color: rgb(204, 238, 255);">
                <div style="text-align: center;">130%</div>
              </td>
            </tr>
            <tr>
              <td style="width: 20%; vertical-align: top;">&#160;</td>
              <td style="width: 20%; vertical-align: top;">
                <div style="text-align: center;">60%</div>
              </td>
              <td style="width: 20%; vertical-align: top;">
                <div style="text-align: center;">120%</div>
              </td>
            </tr>
            <tr>
              <td style="width: 20%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
              <td style="width: 20%; vertical-align: top; background-color: rgb(204, 238, 255);">
                <div style="text-align: center;">55%</div>
              </td>
              <td style="width: 20%; vertical-align: top; background-color: rgb(204, 238, 255);">
                <div style="text-align: center;">110%</div>
              </td>
            </tr>
            <tr>
              <td style="width: 20%; vertical-align: top;">
                <div style="text-align: justify; font-weight: bold;">Target Level</div>
              </td>
              <td style="width: 20%; vertical-align: top;">
                <div style="text-align: center;">50%</div>
              </td>
              <td style="width: 20%; vertical-align: top;">
                <div style="text-align: center;">100%</div>
              </td>
            </tr>
            <tr>
              <td style="width: 20%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
              <td style="width: 20%; vertical-align: top; background-color: rgb(204, 238, 255);">
                <div style="text-align: center;">45%</div>
              </td>
              <td style="width: 20%; vertical-align: top; background-color: rgb(204, 238, 255);">
                <div style="text-align: center;">90%</div>
              </td>
            </tr>
            <tr>
              <td style="width: 20%; vertical-align: top;">&#160;</td>
              <td style="width: 20%; vertical-align: top;">
                <div style="text-align: center;">40%</div>
              </td>
              <td style="width: 20%; vertical-align: top;">
                <div style="text-align: center;">80%</div>
              </td>
            </tr>
            <tr>
              <td style="width: 20%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
              <td style="width: 20%; vertical-align: top; background-color: rgb(204, 238, 255);">
                <div style="text-align: center;">35%</div>
              </td>
              <td style="width: 20%; vertical-align: top; background-color: rgb(204, 238, 255);">
                <div style="text-align: center;">70%</div>
              </td>
            </tr>
            <tr>
              <td style="width: 20%; vertical-align: top;">&#160;</td>
              <td style="width: 20%; vertical-align: top;">
                <div style="text-align: center;">30%</div>
              </td>
              <td style="width: 20%; vertical-align: top;">
                <div style="text-align: center;">60%</div>
              </td>
            </tr>
            <tr>
              <td style="width: 20%; vertical-align: top; background-color: rgb(204, 238, 255);">
                <div style="text-align: justify; font-weight: bold;">Threshold Level</div>
              </td>
              <td style="width: 20%; vertical-align: top; background-color: rgb(204, 238, 255);">
                <div style="text-align: center;">25%</div>
              </td>
              <td style="width: 20%; vertical-align: top; background-color: rgb(204, 238, 255);">
                <div style="text-align: center;">50%</div>
              </td>
            </tr>

        </table>
      </div>
      <div><br>
      </div>
      <div style="text-align: justify; font-style: italic;">There is no minimum number of shares or other consideration that you will receive, and no shares will be earned, if the percentile rank is below the 25th percentile in a Performance Period.</div>
      <div><br>
      </div>
      <div style="text-align: justify; text-indent: 72pt;"><font style="font-weight: bold; color: rgb(0, 0, 0);">(b)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<font style="font-weight: bold;">Rules of Calculation:</font></div>
      <div>&#160;</div>
      <div>
        <div style="text-indent: 108pt;"><font style="font-weight: bold; color: rgb(0, 0, 0);">&#160;(i)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;If the Company&#8217;s absolute TSR is negative over the applicable Performance Period, the pay-out will not exceed 100% of Target for that
          Performance Period, even if the percentile rank exceeds the 50<sup style="vertical-align: text-top; line-height: 1; font-size: smaller;">th</sup> percentile (the &#8220;<font style="font-weight: bold; font-style: italic;">Negative TSR Cap</font>&#8221;).</div>
      </div>
      <div> <br>
      </div>
      <div style="text-align: justify; text-indent: 108pt;"><font style="font-weight: bold; color: rgb(0, 0, 0);">&#160;(ii)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160; Except as modified in Section 3(b)(iii) or 3(b)(iv) below, for purposes of computing TSR, the stock price at the beginning
        of the Performance Period will be the average closing price of a share of common stock over the 20 trading days beginning on the first day of the Performance Period, and the stock price at the end of the Performance Period will be the average
        closing price of a share of common stock over the 20 trading days preceding and including the last day of the Performance Period, adjusted for changes in capital structure; <font style="font-style: italic;">provided, however</font>, that TSR will
        be negative one hundred percent (-100%) if a company: (A) files for bankruptcy, reorganization, or liquidation under any chapter of the U.S. Bankruptcy Code; (B) is the subject of an involuntary bankruptcy proceeding that is not dismissed within 30
        days; (C) is the subject of a stockholder approved plan of liquidation or dissolution; or (D) ceases to conduct substantial business operations.</div>
      <div>&#160;</div>
      <div id="DSPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
        <div id="DSPFPageBreak" style="page-break-after: always;">
          <hr style="margin: 4px 0px; width: 100%; border-width: 0px; height: 2px; color: rgb(0, 0, 0); background-color: rgb(0, 0, 0); clear: both;" noshade="noshade"></div>
      </div>
      <div style="text-align: justify; text-indent: 108pt;"><font style="font-weight: bold; color: rgb(0, 0, 0);">&#160;(iii)</font>&#160;&#160;&#160;&#160;&#160;&#160; Companies will be removed from the Comparison Group if they undergo a Specified Corporate Change. A company that is
        removed from the Comparison Group before the measurement date will not be included at all in the computation of relative TSR. A company in the Comparison Group will be deemed to have undergone a <font style="font-weight: bold; font-style: italic;">Specified

          Corporate Change</font><font style="font-style: italic;"> if </font>it (A) ceases to be a domestically domiciled publicly traded company on a national stock exchange or market system, unless such cessation of such listing is due to a low stock
        price or low trading volume; (B) has gone private; (C) has reincorporated in a foreign (e.g., non-U.S.) jurisdiction, regardless of whether it is a reporting company in that or another jurisdiction; or (D) has been acquired by another company
        (whether by a peer company or otherwise, but not including internal reorganizations), or has sold all or substantially all of its assets.</div>
      <div>&#160;</div>
      <div style="text-align: justify; text-indent: 108pt;"><font style="font-weight: bold; color: rgb(0, 0, 0);">&#160;(iv)</font>&#160;&#160;&#160;&#160;&#160;&#160; The Company&#8217;s Compensation Committee may in its good faith discretion calculate the TSRs and TSR Percentile Rank using a
        subscription service (such as Bloomberg) provided such calculation is (A) consistently applied, (B) intended to ease the burden of administering this Award, and (C) intended to preserve the overall intent of this Award.</div>
      <div>&#160;</div>
      <div style="text-align: justify; text-indent: 36pt;"><font style="font-weight: bold; color: rgb(0, 0, 0);">4.</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160; &#160; &#160; <font style="font-weight: bold; font-variant: small-caps;"><font style="text-transform: uppercase;">Vesting And
            Termination of Continuous Service.&#160;</font> </font></div>
      <div>&#160;</div>
      <div style="text-align: justify; text-indent: 72pt;"><font style="font-weight: bold; color: rgb(0, 0, 0);">(a)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<font style="font-weight: bold;">In General</font>.&#160; Subject to the limitations contained herein, your Award will vest, if
        at all, in accordance with Section 1 above, provided that vesting will cease upon the termination of your Continuous Service except as set forth below.&#160; Upon termination of your Continuous Service, the PRSUs that were not vested on the date of such
        termination will be forfeited at no cost to the Company, and you will have no further right, title or interest in the PRSUs or the shares of Common Stock to be issued in respect of the Award except as set forth below.</div>
      <div>&#160;</div>
      <div style="text-align: justify; text-indent: 72pt;"><font style="font-weight: bold; color: rgb(0, 0, 0);">(b)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; &#160; <font style="font-weight: bold;">Change in Control</font>.</div>
      <div>&#160;</div>
      <div style="text-align: justify; text-indent: 108pt;"><font style="font-weight: bold; color: rgb(0, 0, 0);">&#160;(i)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; If a Change in Control Termination (as such term is defined in the Company&#8217;s Severance Benefit Plan adopted October 18,
        2018 (the &#8220;<font style="font-weight: bold; font-style: italic;">Severance Plan</font>&#8221;)) occurs during the Change in Control Protection Period (as such term is defined in the Severance Plan), the Award will pay-out at Target and the Target PRSUs
        subject to such Award that have not already vested will vest immediately upon the Change in Control Termination.</div>
      <div>&#160;</div>
      <div style="text-align: justify; text-indent: 108pt;"><font style="font-weight: bold; color: rgb(0, 0, 0);">&#160;(ii)</font>&#160;&#160;&#160;&#160;&#160; If a Change in Control (as such term is defined in the Severance Plan) occurs and your Award will not be assumed, continued
        or substituted by the successor or acquiror entity in such Change in Control, the Award will pay-out at Target and the Target PRSUs subject to such Award that have not already vested will vest immediately upon the Change in Control.</div>
      <div>&#160;</div>
      <div id="DSPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
        <div id="DSPFPageBreak" style="page-break-after: always;">
          <hr style="margin: 4px 0px; width: 100%; border-width: 0px; height: 2px; color: rgb(0, 0, 0); background-color: rgb(0, 0, 0); clear: both;" noshade="noshade"></div>
      </div>
      <div style="text-align: justify; text-indent: 108pt;"><font style="font-weight: bold; color: rgb(0, 0, 0);">&#160;(iii)</font>&#160;&#160;&#160;&#160;&#160; If a Change in Control (as such term is defined in the Severance Plan) occurs and your Award will be assumed, continued or
        substituted by the successor or acquiror entity in such Change in Control, the PRSUs subject to such Award will automatically convert upon the Change in Control to time-vested restricted stock units (&#8220;<font style="font-weight: bold; font-style: italic;">RSUs</font>&#8221;) at a rate of one RSU for each of the Target number of PRSUs.&#160; The RSUs will not be subject to the relative TSR performance measure described in Section 1 above and instead will vest at Target at the end of the applicable
        Performance Periods outlined in Section 2(b) above that are still remaining at the time of the Change in Control.&#160; Such RSUs will be subject to further acceleration in the case of a Change in Control Termination during the Change in Control
        Protection Period (as such term is defined in the Severance Plan).</div>
      <div>&#160;</div>
      <div style="text-align: justify; text-indent: 108pt;"><font style="font-weight: bold; color: rgb(0, 0, 0);">&#160;(iv)</font>&#160;&#160;&#160;&#160;&#160; Notwithstanding anything to the contrary in this Agreement or the Severance Plan, if you are a party to a prior written
        employment agreement, change of control agreement, or plan or other similar written agreement or plan (each, a &#8220;<font style="font-weight: bold; font-style: italic;">Prior Agreement</font>&#8221;), that provides, in certain circumstances, for greater
        benefits regarding the accelerated vesting of equity awards (including PRSUs) following a Change in Control of the Company or similar transaction, the terms of such Prior Agreement shall control the definition of the term &#8220;<font style="font-style: italic;">Change in Control</font>&#8221; (or any term used therein of similar import) and the terms and conditions by which the vesting of the PRSUs may be accelerated as a result of a Change in Control, as well as the benefits that may otherwise be
        available to you upon a Change in Control.</div>
      <div>&#160;</div>
      <div style="text-align: justify; text-indent: 36pt;"><font style="font-weight: bold; color: rgb(0, 0, 0);">5.</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; &#160;&#160; <font style="text-transform: uppercase;"><font style="font-weight: bold; font-variant: small-caps;">Adjustments to Number
            of Shares</font><font style="font-weight: bold;">.</font></font></div>
      <div>&#160;</div>
      <div style="text-align: justify; text-indent: 72pt;"><font style="font-weight: bold; color: rgb(0, 0, 0);">(a)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; The number of PRSUs subject to your Award may be adjusted from time to time for Capitalization Adjustments, as provided in
        the Plan.</div>
      <div>&#160;</div>
      <div style="text-align: justify; text-indent: 72pt;"><font style="font-weight: bold; color: rgb(0, 0, 0);">(b)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160; Any additional PRSUs that become subject to the Award pursuant to this Section 5 and Section 9, if any, will be subject, in a
        manner determined by the Board, to the same forfeiture restrictions, restrictions on transferability, and time and manner of delivery as applicable to the other PRSUs covered by your Award.</div>
      <div>&#160;</div>
      <div style="text-align: justify; text-indent: 72pt;"><font style="font-weight: bold; color: rgb(0, 0, 0);">(c)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160; Notwithstanding the provisions of this Section 5, no fractional shares or rights for fractional shares of Common Stock will
        be created pursuant to this Section 5.&#160; The Board will, in its discretion, determine an equivalent benefit for any fractional shares or fractional shares that might be created by the adjustments referred to in this Section 5.</div>
      <div>&#160;</div>
      <div style="text-align: justify; text-indent: 36pt;"><font style="font-weight: bold; color: rgb(0, 0, 0);">6.</font>&#160;&#160;&#160;&#160;&#160;&#160; &#160;<font style="text-transform: uppercase;"> </font><font style="font-weight: bold; font-variant: small-caps; text-transform: uppercase;">Securities Law Compliance</font><font style="font-weight: bold; text-transform: uppercase;">.</font><font style="text-transform: uppercase;">&#160;</font> You may not be issued any shares in respect of your Award unless either (i) the
        shares are registered under the Securities Act; or (ii) the Company has determined that such issuance would be exempt from the registration requirements of the Securities Act. Your Award also must comply with other applicable laws and regulations
        governing the Award, and you will not receive such shares if the Company determines that such receipt would not be in material compliance with such laws and regulations.</div>
      <div>&#160;</div>
      <div style="text-align: justify; text-indent: 36pt;"><font style="font-weight: bold; color: rgb(0, 0, 0);">7.</font>&#160;&#160;&#160;&#160;&#160;&#160; &#160;&#160; <font style="font-weight: bold; font-variant: small-caps; text-transform: uppercase;">Transfer Restrictions.</font>&#160; Prior
        to the time that shares of Common Stock have been delivered to you, you may not transfer, pledge, sell or otherwise dispose of this Award or the shares issuable in respect of your Award, except as expressly provided in this Section 7.&#160; For example,
        you may not use shares that may be issued in respect of your Award as security for a loan.&#160; The restrictions on transfer set forth herein will lapse upon delivery to you of shares in respect of your vested Award.</div>
      <div>&#160;</div>
      <div id="DSPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
        <div id="DSPFPageBreak" style="page-break-after: always;">
          <hr style="margin: 4px 0px; width: 100%; border-width: 0px; height: 2px; color: rgb(0, 0, 0); background-color: rgb(0, 0, 0); clear: both;" noshade="noshade"></div>
      </div>
      <div style="text-align: justify; text-indent: 72pt;"><font style="font-weight: bold; color: rgb(0, 0, 0);">(a)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<font style="font-weight: bold;">Death</font>.&#160; Your Award is transferable by will and by the laws of descent and
        distribution.&#160; In addition, upon receiving written permission from the Board or its duly authorized designee, you may, by delivering written notice to the Company, in a form provided by or otherwise satisfactory to the Company and any broker
        designated by the Company to effect transactions under the Plan, designate a third party who, in the event of your death, will thereafter be entitled to receive any distribution of Common Stock or other consideration to which you were entitled at
        the time of your death pursuant to this Agreement.&#160; In the absence of such a designation, your executor or administrator of your estate will be entitled to receive, on behalf of your estate, such Common Stock or other consideration.</div>
      <div>&#160;</div>
      <div style="text-align: justify; text-indent: 72pt;"><font style="font-weight: bold; color: rgb(0, 0, 0);">(b)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; <font style="font-weight: bold;">Certain Trusts.</font>&#160; Upon receiving written permission from the Board or its duly
        authorized designee, you may transfer your Award to a trust if you are considered to be the sole beneficial owner (determined under Section 671 of the Code and applicable state law) while the Award is held in the trust, provided that you and the
        trustee enter into transfer and other agreements required by the Company.</div>
      <div>&#160;</div>
      <div style="text-align: justify; text-indent: 72pt;"><font style="font-weight: bold; color: rgb(0, 0, 0);">(c)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<font style="font-weight: bold;">Domestic Relations Orders.</font>&#160; Upon receiving written permission from the Board or its
        duly authorized designee, and provided that you and the designated transferee enter into transfer and other agreements required by the Company, you may transfer your Award or your right to receive the distribution of Common Stock or other
        consideration thereunder, pursuant to a domestic relations order that contains the information required by the Company to effectuate the transfer.&#160; You are encouraged to discuss the proposed terms of any division of this Award with the Company
        prior to finalizing the domestic relations order to help ensure the required information is contained within the domestic relations order.</div>
      <div>&#160;</div>
      <div style="text-align: justify; text-indent: 36pt;"><font style="font-weight: bold; color: rgb(0, 0, 0);">8.</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160; &#160; &#160; <font style="font-weight: bold; font-variant: small-caps; text-transform: uppercase;">Date of Issuance.</font></div>
      <div>&#160;</div>
      <div style="text-align: justify; text-indent: 72pt;"><font style="font-weight: bold; color: rgb(0, 0, 0);">(a)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;If the Award is exempt from application of Section 409A of the Code and the regulations and other guidance thereunder and
        any state law of similar effect (collectively <font style="font-weight: bold;">&#8220;</font><font style="font-weight: bold; font-style: italic;">Section</font>&#160;<font style="font-weight: bold; font-style: italic;">409A</font><font style="font-weight: bold;">&#8221;</font>), the Company will deliver to you a number of shares of the Company&#8217;s Common Stock equal to the number of vested PRSUs subject to your Award, including any additional PRSUs received pursuant to Section 5 above that relate to those
        vested PRSUs on the applicable vesting date(s).&#160; However, if a scheduled delivery date falls on a date that is not a business day, such delivery date will instead fall on the next following business day.&#160; Notwithstanding the foregoing, in the event
        that (i) you are subject to the Company&#8217;s policy permitting officers and directors to sell shares only during certain &#8220;window&#8221; periods, in effect from time to time (the &#8220;<font style="font-weight: bold; font-style: italic;">Policy</font>&#8221;) or you
        are otherwise prohibited from selling shares of the Company&#8217;s Common Stock in the public market and any shares covered by your Award are scheduled to be delivered on a day (the &#8220;<font style="font-weight: bold; font-style: italic;">Original
          Distribution Date</font>&#8221;) that does not occur during an open &#8220;window period&#8221; applicable to you or a day on which you are permitted to sell shares of the Company&#8217;s Common Stock pursuant to a written plan that meets the requirements of Rule 10b5-1
        under the Exchange Act, in each case as determined by the Company in accordance with the Policy, or does not occur on a date when you are otherwise permitted to sell shares of the Company&#8217;s Common Stock on the open market, and (ii) the Company
        elects not to satisfy its tax withholding obligations (if any) by withholding shares from your distribution, then such shares will not be delivered on such Original Distribution Date and will instead be delivered on the first business day of the
        next occurring open &#8220;window period&#8221; applicable to you pursuant to such policy (regardless of whether you are still providing Continuous Services at such time) or the next business day when you are not prohibited from selling shares of the Company&#8217;s
        Common Stock in the open market, but in no event later than the fifteenth day of the third calendar month of the calendar year following the calendar year in which the shares covered by the Award vest.&#160; Delivery of the shares pursuant to the
        provisions of this Section 8(a) is intended to comply with the requirements for the short-term deferral exemption available under Treasury Regulation 1.409A-1(b)(4) and will be construed and administered in such manner.&#160; The form of such delivery
        of the shares (<font style="font-style: italic;">e.g.</font>, a stock certificate or electronic entry evidencing such shares) will be determined by the Company.</div>
      <div>&#160;</div>
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      <div style="text-align: justify; text-indent: 72pt;"><font style="font-weight: bold; color: rgb(0, 0, 0);">(b)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160; The provisions of this Section 8(b) are intended to apply if the Award is subject to Section 409A because of the terms of a
        severance arrangement or other agreement between you and the Company that provides for acceleration of vesting of the Award upon your separation from service (as such term is defined in section 409A(a)(2)(A)(i) of the Code and applicable guidance
        thereunder (&#8220;<font style="font-weight: bold; font-style: italic;">Separation From Service</font>&#8221;) and such severance benefit does not satisfy the requirements for an exemption from application of Section 409A provided under Treasury Regulations
        Sections 1.409A-1(b)(4) or 1.409A-1(b)(9) (&#8220;<font style="font-weight: bold; font-style: italic;">Non-Exempt Severance Arrangement</font>&#8221;).&#160; If the Award is subject to and not exempt from application of Section 409A due to application of a
        Non-Exempt Severance Arrangement, the following provisions in this Section 8(b) will supersede anything to the contrary in Section 8(a).</div>
      <div>&#160;</div>
      <div style="text-align: justify; text-indent: 108pt;"><font style="font-weight: bold; color: rgb(0, 0, 0);">&#160;(i)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160; If the Award vests in ordinary course during your Continuous Service in accordance with the vesting schedule set forth in
        the Grant Notice, in no event will the shares to be issued in respect of your Award be issued any later than the later of: (A) December 31<sup style="vertical-align: text-top; line-height: 1; font-size: smaller;">st</sup> of the calendar year that
        includes the applicable vesting date, or (B) the 60<sup style="vertical-align: text-top; line-height: 1; font-size: smaller;">th</sup> day that follows the applicable vesting date.</div>
      <div>&#160;</div>
      <div style="text-align: justify; text-indent: 108pt;"><font style="font-weight: bold; color: rgb(0, 0, 0);">&#160;(ii)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; If the Award accelerates vesting under the terms of your Non-Exempt Severance Arrangement in connection with your
        Separation From Service, and such vesting acceleration provisions of your Non-Exempt Severance Arrangement were in effect as of the Date of Grant of the Award and therefore part of the terms of the Award as of the Date of Grant, then the shares
        will be earlier issued in respect of your Award upon your Separation From Service in accordance with the terms of the Non-Exempt Severance Arrangement, but in no event later than the 60<sup style="vertical-align: text-top; line-height: 1; font-size: smaller;">th</sup> day that follows the date of your Separation From Service.&#160; However, if at the time the shares would otherwise be issued you are subject to the distribution limitations contained in section 409A of the Code
        applicable to &#8220;specified employees&#8221; as defined in section 409A(a)(2)(B)(i) of the Code and applicable guidance thereunder, such share issuances will not be made before the date which is six months following the date of your Separation From Service,
        or, if earlier, the date of your death that occurs within such six month period.</div>
      <div>&#160;</div>
      <div style="text-align: justify; text-indent: 108pt;"><font style="font-weight: bold; color: rgb(0, 0, 0);">&#160;(iii)</font>&#160;&#160;&#160;&#160;&#160;&#160; If the Award accelerates vesting under the terms of your Non-Exempt Severance Arrangement in connection with your
        Separation From Service, and such vesting acceleration provisions of your Non-Exempt Severance Arrangement were not in effect as of the Date of Grant of the Award and therefore not a part of the terms of the Award on the Date of Grant, then such
        acceleration of vesting of the Award will not accelerate the issuance date of the shares, but the shares will instead be issued on the same schedule as set forth on the Grant Notice as if they had vested in ordinary course during your Continuous
        Service, notwithstanding the vesting acceleration of the Award.&#160; Such issuance schedule is intended to satisfy the requirements of payment on a specified date or pursuant to a fixed schedule, as provided under Treas. Reg. 1.409A-3(a)(4).</div>
      <div>&#160;</div>
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      <div style="text-align: justify; text-indent: 72pt;"><font style="font-weight: bold; color: rgb(0, 0, 0);">(c)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; &#160; The provisions in this Agreement for delivery of the shares in respect of the Award are intended either to comply with the
        requirements of Section 409A or to provide a basis for exemption from such requirements so that the delivery of the shares will not trigger the additional tax imposed under Section 409A, and any ambiguities herein will be so interpreted.</div>
      <div>&#160;</div>
      <div style="text-align: justify; text-indent: 36pt;"><font style="font-weight: bold; color: rgb(0, 0, 0);">9.</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<font style="text-transform: uppercase;">&#160;&#160;</font><font style="font-weight: bold; font-variant: small-caps; text-transform: uppercase;">Dividends.</font><font style="font-weight: bold;">&#160;&#160;&#160;&#160; </font>You will be entitled to receive payments equal to any cash dividends and other distributions paid with respect to a corresponding number of shares to be issued in respect
        of the PRSUs covered by your Award, provided that if any such dividends or distributions are paid in shares, the Fair Market Value of such shares will be converted into additional PRSUs covered by the Award, and further provided that such
        additional PRSUs will be subject to the same forfeiture restrictions and restrictions on transferability as apply to the PRSUs subject to the Award with respect to which they relate.</div>
      <div>&#160;</div>
      <div style="text-align: justify; text-indent: 36pt;"><font style="font-weight: bold; color: rgb(0, 0, 0);">10.</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<font style="text-transform: uppercase;">&#160;</font><font style="font-weight: bold; font-variant: small-caps; text-transform: uppercase;">Restrictive Legends.</font>&#160; The shares issued in respect of your Award will be endorsed with appropriate legends determined by the Company.</div>
      <div>&#160;</div>
      <div style="text-align: justify; text-indent: 36pt;"><font style="font-weight: bold; color: rgb(0, 0, 0);">11.</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<font style="text-transform: uppercase;">&#160;<font style="font-weight: bold; font-variant: small-caps;">Award not a Service
            Contract</font><font style="font-weight: bold;">.</font></font></div>
      <div>&#160;</div>
      <div style="text-align: justify; text-indent: 72pt;"><font style="font-weight: bold; color: rgb(0, 0, 0);">(a)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;Your Continuous Service with the Company or an Affiliate is not for any specified term and may be terminated by you or by
        the Company or an Affiliate at any time, for any reason, with or without cause and with or without notice.&#160; Nothing in this Agreement (including, but not limited to, the vesting of your Award pursuant to Section 1 herein or the issuance of the
        shares in respect of your Award), the Plan or any covenant of good faith and fair dealing that may be found implicit in this Agreement or the Plan will:&#160; (i) confer upon you any right to continue in the employ of, or affiliation with, the Company
        or an Affiliate; (ii) constitute any promise or commitment by the Company or an Affiliate regarding the fact or nature of future positions, future work assignments, future compensation or any other term or condition of employment or affiliation;
        (iii) confer any right or benefit under this Agreement or the Plan unless such right or benefit has specifically accrued under the terms of this Agreement or Plan; or (iv) deprive the Company of the right to terminate you at will and without regard
        to any future vesting opportunity that you may have.</div>
      <div>&#160;</div>
      <div style="text-align: justify; text-indent: 72pt;"><font style="font-weight: bold; color: rgb(0, 0, 0);">(b)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160; By accepting this Award, you acknowledge and agree that the right to continue vesting in the Award pursuant to Section 1 is
        earned only by continuing as an employee, director or consultant at the will of the Company (not through the act of being hired, being granted this Award or any other award or benefit) and that the Company has the right to reorganize, sell,
        spin-out or otherwise restructure one or more of its businesses or Affiliates at any time or from time to time, as it deems appropriate (a &#8220;reorganization&#8221;).&#160; You further acknowledge and agree that such a reorganization could result in the
        termination of your Continuous Service, or the termination of Affiliate status of your employer and the loss of benefits available to you under this Agreement, including but not limited to, the termination of the right to continue vesting in the
        Award.&#160; You further acknowledge and agree that this Agreement, the Plan, the transactions contemplated hereunder and the vesting schedule set forth herein or any covenant of good faith and fair dealing that may be found implicit in any of them do
        not constitute an express or implied promise of continued engagement as an employee or consultant for the term of this Agreement, for any period, or at all, and will not interfere in any way with your right or the Company&#8217;s right to terminate your
        Continuous Service at any time, with or without cause and with or without notice.</div>
      <div>&#160;</div>
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      <div style="text-align: justify; text-indent: 36pt;"><font style="font-weight: bold; color: rgb(0, 0, 0);">12.</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<font style="text-transform: uppercase;">&#160;&#160;<font style="font-weight: bold; font-variant: small-caps;">Withholding
            Obligations.</font></font></div>
      <div>&#160;</div>
      <div style="text-align: justify; text-indent: 72pt;"><a name="OLE_LINK5"></a><a name="OLE_LINK6"></a><font style="font-weight: bold; color: rgb(0, 0, 0);">(a)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160; On or before the time you receive a distribution of shares subject to your
        Award, or at any time thereafter as requested by the Company, you hereby authorize any required withholding (if any) from the Common Stock issuable to you and/or otherwise agree to make adequate provision in cash for any sums required to satisfy
        the federal, state, local and foreign tax withholding obligations (if any) of the Company or any Affiliate which arise in connection with your Award (the &#8220;<font style="font-weight: bold; font-style: italic;">Withholding Taxes</font>&#8221;).&#160;
        Additionally, the Company may, in its sole discretion, satisfy all or any portion of the Withholding Taxes obligation relating to your Award by any of the following means or by a combination of such means: (i) withholding from any compensation
        otherwise payable to you by the Company; (ii) causing you to tender a cash payment; or (iii) withholding shares of Common Stock from the shares of Common Stock issued or otherwise issuable to you in connection with the Award with a Fair Market
        Value (measured as of the date shares of Common Stock are issued pursuant to Section 8) equal to the amount of such Withholding Taxes; provided, however, that the number of such shares of Common Stock so withheld will not exceed the amount
        necessary to satisfy the Company&#8217;s required tax withholding obligations using the minimum statutory withholding rates for federal, state, local and foreign tax purposes, including payroll taxes, that are applicable to supplemental taxable income.</div>
      <div>&#160;</div>
      <div style="text-align: justify; text-indent: 72pt;"><font style="font-weight: bold; color: rgb(0, 0, 0);">(b)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160; &#160; Unless the tax withholding obligations of the Company and/or any Affiliate are satisfied, the Company will have no
        obligation to deliver to you any Common Stock.</div>
      <div>&#160;</div>
      <div style="text-align: justify; text-indent: 72pt;"><font style="font-weight: bold; color: rgb(0, 0, 0);">(c)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; In the event the Company&#8217;s obligation to withhold arises prior to the delivery to you of Common Stock or it is determined
        after the delivery of Common Stock to you that the amount of the Company&#8217;s withholding obligation was greater than the amount withheld by the Company, you agree to indemnify and hold the Company harmless from any failure by the Company to withhold
        the proper amount.</div>
      <div>&#160;</div>
      <div style="text-align: justify; text-indent: 72pt;"><font style="font-weight: bold; color: rgb(0, 0, 0);">(d)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;If specified in your Grant Notice and permitted by the Company, you may direct the Company to withhold shares of Common
        Stock with a Fair Market Value (measured as of the date shares of Common Stock are issued pursuant to Section 8) equal to the amount of such Withholding Taxes; provided, however, that the number of such shares of Common Stock so withheld will not
        exceed the amount necessary to satisfy the Company&#8217;s required tax withholding obligations using the minimum statutory withholding rates for federal, state, local and foreign tax purposes, including payroll taxes, that are applicable to supplemental
        taxable income.</div>
      <div>&#160;</div>
      <div style="text-align: justify; text-indent: 36pt;"><font style="font-weight: bold; color: rgb(0, 0, 0);">13.</font>&#160;&#160;&#160;&#160;&#160;&#160; &#160; <font style="font-weight: bold; font-variant: small-caps;"><font style="text-transform: uppercase;">Unsecured Obligation</font><font style="text-transform: uppercase;">.</font></font><font style="text-transform: uppercase;">&#160;</font> Your Award is unfunded, and as a holder of a vested Award, you will be considered an unsecured creditor of the Company with respect to the
        Company&#8217;s obligation, if any, to issue shares pursuant to this Agreement.&#160; You will not have voting or any other rights as a stockholder of the Company with respect to the shares to be issued pursuant to this Agreement until such shares are issued
        to you pursuant to Section 8 of this Agreement.&#160;&#160; Upon such issuance, you will obtain full voting and other rights as a stockholder of the Company.&#160; Nothing contained in this Agreement, and no action taken pursuant to its provisions, will create or
        be construed to create a trust of any kind or a fiduciary relationship between you and the Company or any other person.</div>
      <div>&#160;</div>
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      </div>
      <div style="text-align: justify; text-indent: 36pt;"><font style="font-weight: bold; color: rgb(0, 0, 0);">14.</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; <font style="font-weight: bold; font-variant: small-caps; text-transform: uppercase;">Other Documents</font><font style="font-variant: small-caps; text-transform: uppercase;">.</font>&#160; You hereby acknowledge receipt or the right to receive a document providing the information required by Rule 428(b)(1) promulgated under the Securities Act, which includes the
        Plan prospectus.&#160; In addition, you acknowledge receipt of the Company&#8217;s insider-trading policy and agree that you may sell shares only in compliance with such policy, in effect from time to time.</div>
      <div>&#160;</div>
      <div style="text-align: justify; text-indent: 36pt;"><font style="font-weight: bold; color: rgb(0, 0, 0);">15.</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; <font style="font-weight: bold; font-variant: small-caps; text-transform: uppercase;">Notices</font><font style="font-weight: bold; text-transform: uppercase;">.</font>&#160; Any notices provided for in your Award or the Plan will be given in writing and will be deemed effectively given upon receipt or, in the case of notices delivered by the Company to
        you, five days after deposit in the United States mail, postage prepaid, addressed to you at the last address you provided to the Company.&#160; Notwithstanding the foregoing, the Company may, in its sole discretion, decide to deliver any documents
        related to participation in the Plan and this Award by electronic means or to request your consent to participate in the Plan by electronic means.&#160; You hereby consent to receive such documents by electronic delivery and, if requested, to agree to
        participate in the Plan through an on-line or electronic system established and maintained by the Company or another third party designated by the Company.</div>
      <div>&#160;</div>
      <div style="text-align: justify; text-indent: 36pt;"><font style="font-weight: bold; color: rgb(0, 0, 0);">16.</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<font style="font-weight: bold; text-transform: uppercase;"><font style="font-variant: small-caps;">Miscellaneous</font>.</font></div>
      <div>&#160;</div>
      <div style="text-align: justify; text-indent: 72pt;"><font style="font-weight: bold; color: rgb(0, 0, 0);">(a)</font>&#160;&#160;&#160;&#160;&#160;&#160; &#160;&#160; The rights and obligations of the Company under your Award will be transferable to any one or more persons or entities, and
        all covenants and agreements hereunder will inure to the benefit of, and be enforceable by the Company&#8217;s successors and assigns. Your rights and obligations under your Award may only be assigned with the prior written consent of the Company.</div>
      <div>&#160;</div>
      <div style="text-align: justify; text-indent: 72pt;"><font style="font-weight: bold; color: rgb(0, 0, 0);">(b)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; You agree upon request to execute any further documents or instruments necessary or desirable in the sole determination of
        the Company to carry out the purposes or intent of your Award.</div>
      <div>&#160;</div>
      <div style="text-align: justify; text-indent: 72pt;"><font style="font-weight: bold; color: rgb(0, 0, 0);">(c)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; You acknowledge and agree that you have reviewed your Award in its entirety, have had an opportunity to obtain the advice of
        counsel prior to executing and accepting your Award, and fully understand all provisions of your Award.</div>
      <div>&#160;</div>
      <div style="text-align: justify; text-indent: 72pt;"><font style="font-weight: bold; color: rgb(0, 0, 0);">(d)</font>&#160;&#160;&#160;&#160;&#160; &#160;&#160; This Agreement will be subject to all applicable laws, rules, and regulations, and to such approvals by any governmental
        agencies or national securities exchanges as may be required.</div>
      <div>&#160;</div>
      <div style="text-align: justify; text-indent: 72pt;"><font style="font-weight: bold; color: rgb(0, 0, 0);">(e)</font>&#160;&#160;&#160;&#160;&#160;&#160; &#160;&#160; All obligations of the Company under the Plan and this Agreement will be binding on any successor to the Company, whether
        the existence of such successor is the result of a direct or indirect purchase, merger, consolidation, or otherwise, of all or substantially all of the business and/or assets of the Company.</div>
      <div>&#160;</div>
      <div style="text-align: justify; text-indent: 36pt;"><font style="font-weight: bold; color: rgb(0, 0, 0);">17.</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<font style="font-weight: bold; font-variant: small-caps; text-transform: uppercase;">Governing Plan Document</font><font style="font-weight: bold; text-transform: uppercase;">.</font>&#160; Your Award is subject to all the provisions of the Plan, the provisions of which are hereby made a part of your Award, and is further subject to all interpretations, amendments,
        rules and regulations which may from time to time be promulgated and adopted pursuant to the Plan.&#160; Except as expressly provided herein, in the event of any conflict between the provisions of your Award and those of the Plan, the provisions of the
        Plan will control.</div>
      <div>&#160;</div>
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      </div>
      <div style="text-align: justify; text-indent: 36pt;"><font style="font-weight: bold; color: rgb(0, 0, 0);">18.</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<font style="font-weight: bold; font-variant: small-caps; text-transform: uppercase;">Severability.</font><font style="text-transform: uppercase;">&#160;</font> If all or any part of this Agreement or the Plan is declared by any court or governmental authority to be unlawful or invalid, such unlawfulness or invalidity will not invalidate any portion of this
        Agreement or the Plan not declared to be unlawful or invalid. Any Section of this Agreement (or part of such a Section) so declared to be unlawful or invalid will, if possible, be construed in a manner which will give effect to the terms of such
        Section or part of a Section to the fullest extent possible while remaining lawful and valid.</div>
      <div>&#160;</div>
      <div style="text-align: justify; text-indent: 36pt;"><font style="font-weight: bold; color: rgb(0, 0, 0);">19.</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; <font style="font-weight: bold; font-variant: small-caps; text-transform: uppercase;">Effect on Other Employee Benefit
          Plans</font><font style="font-weight: bold;"><font style="text-transform: uppercase;">.</font> </font>The value of the Award subject to this Agreement shall not be included as compensation, earnings, salaries, or other similar terms used when
        calculating your benefits under any employee benefit plan sponsored by the Company or any Affiliate, except as such plan otherwise expressly provides. The Company expressly reserves its rights to amend, modify, or terminate any of the Company&#8217;s or
        any Affiliate&#8217;s employee benefit plans.</div>
      <div>&#160;</div>
      <div style="text-align: justify; text-indent: 36pt;"><font style="font-weight: bold; color: rgb(0, 0, 0);">20.</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160; <font style="font-weight: bold; font-variant: small-caps; text-transform: uppercase;">Choice of Law</font><font style="font-weight: bold; text-transform: uppercase;">.</font><font style="text-transform: uppercase;">&#160;</font> The interpretation, performance and enforcement of this Agreement will be governed by the law of the state of California without
        regard to such state&#8217;s conflicts of laws rules.</div>
      <div>&#160;</div>
      <div style="text-align: justify; text-indent: 36pt;"><font style="font-weight: bold; color: rgb(0, 0, 0);">21.</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<font style="font-weight: bold; font-variant: small-caps; text-transform: uppercase;">Amendment.</font>&#160; This Agreement may
        not be modified, amended or terminated except by an instrument in writing, signed by you and by a duly authorized representative of the Company. Notwithstanding the foregoing, this Agreement may be amended solely by the Board by a writing which
        specifically states that it is amending this Agreement, so long as a copy of such amendment is delivered to you, and provided that no such amendment adversely affecting your rights hereunder may be made without your written consent. Without
        limiting the foregoing, the Board reserves the right to change, by written notice to you, the provisions of this Agreement in any way it may deem necessary or advisable to carry out the purpose of the grant as a result of any change in applicable
        laws or regulations or any future law, regulation, ruling, or judicial decision, provided that any such change will be applicable only to rights relating to that portion of the Award which is then subject to restrictions as provided herein.</div>
      <div>&#160;</div>
      <div style="text-align: justify; text-indent: 36pt;"><font style="font-weight: bold; color: rgb(0, 0, 0);">22.</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160; <font style="font-weight: bold; font-variant: small-caps; text-transform: uppercase;">Discretion of the Committee.</font>
        Unless otherwise explicitly provided herein, the Compensation Committee of the Board of Directors of the Company, or an authorized successor committee thereto, shall make all determinations required to be made hereunder, including but not limited
        to determinations relating to the achievement of any thresholds or the vesting of any PRSUs hereunder, and shall interpret all provisions of this PRSU Award Agreement and the underlying PRSUs, as it deems necessary or desirable, in its sole and
        absolute discretion. Such determinations and interpretations shall be binding on and conclusive to the Company and you. Without limiting the foregoing, the Company may, in its sole and absolute discretion, delay payments hereunder or make such
        other modifications with respect to the issuance of stock hereunder as it reasonably deems necessary to the extent that (a) audited financials are not complete for any applicable period during the Performance Period and/or (b) the Company has not
        had an adequate opportunity to review the audited financials or confirm the applicable TSR Percentile Ranks.</div>
      <div>&#160;</div>
      <div><br>
      </div>
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<DOCUMENT>
<TYPE>EX-10.46
<SEQUENCE>3
<FILENAME>exhibit10_46.htm
<DESCRIPTION>EXHIBIT 10.46
<TEXT>
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    <div style="text-align: right; font-variant: small-caps; font-weight: bold;">Exhibit 10.46</div>
    <div><br>
    </div>
    <div style="font-weight: bold;">CERTAIN IDENTIFIED INFORMATION HAS BEEN EXCLUDED FROM THE EXHIBIT BECAUSE IT IS BOTH (I) NOT MATERIAL AND (II) WOULD BE COMPETITIVELY HARMFUL IF PUBLICLY DISCLOSED.&#160; SUCH EXCLUDED INFORMATION HAS BEEN MARKED WITH
      &#8220;[***]&#8221;.</div>
    <div><br>
    </div>
    <div></div>
    <div style="text-align: center; font-variant: small-caps;">Research Collaboration, Option and License Agreement</div>
    <div>&#160;</div>
    <div style="text-align: center; font-variant: small-caps;">Between</div>
    <div>&#160;</div>
    <div style="text-align: center; font-variant: small-caps;">Isis Pharmaceuticals, Inc.</div>
    <div>&#160;</div>
    <div style="text-align: center; font-variant: small-caps;">And</div>
    <div>&#160;</div>
    <div style="text-align: center; font-variant: small-caps;">Janssen Biotech Inc.</div>
    <div>&#160;</div>
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      <div style="width: 100%;" id="DSPFPageHeader">Confidential</div>
    </div>
    <div style="text-align: center; font-weight: bold;">RESEARCH COLLABORATION, OPTION AND LICENSE AGREEMENT</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt;">This RESEARCH COLLABORATION, OPTION AND LICENSE AGREEMENT (the &#8220;<font style="font-weight: bold; font-style: italic;">Agreement</font>&#8221;) is entered into as of the 22<sup style="vertical-align: text-top; line-height: 1; font-size: smaller;">nd</sup> day of December, 2014 (the &#8220;<font style="font-weight: bold; font-style: italic;">Effective Date</font>&#8221;), by and between <font style="font-weight: bold; font-variant: small-caps;">Isis
        Pharmaceuticals, Inc.</font>, a Delaware corporation, having its principal place of business at 2855 Gazelle Court, Carlsbad, CA 92010 (&#8220;<font style="font-weight: bold; font-style: italic;">Isis</font>&#8221;), and<font style="font-weight: bold; font-variant: small-caps;"> Janssen Biotech Inc.</font>, a Pennsylvania company, with principal offices located at 800/850 Ridgeview Road, Horsham, PA 19044 (&#8220;<font style="font-weight: bold;"><u>JBI</u></font>&#8221;)&#160; JBI and Isis each may be referred
      to herein individually as a &#8220;<font style="font-weight: bold; font-style: italic;">Party</font>&#8221; or collectively as the &#8220;<font style="font-weight: bold; font-style: italic;">Parties</font>.&#8221;&#160; 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>.&#160; 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-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;">WHEREAS</font><font style="font-size: 10pt;">, Isis possesses certain Patent Rights, Know-How, technology and expertise with respect
        to antisense therapeutics, and has novel and valuable capabilities for the research, discovery, identification, synthesis and development of antisense therapeutics;</font></div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt; font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;">WHEREAS</font><font style="font-size: 10pt;">, JBI has expertise in developing and commercializing human therapeutics, and JBI is
        interested in developing and commercializing antisense therapeutics for initially up to three gene targets implicated in Autoimmune Disease (with the right to add a fourth target by paying an additional fee);</font></div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt; font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;">WHEREAS</font><font style="font-size: 10pt;">, the Parties desire to enter into a collaborative enterprise pursuant to which (i) the
        Parties will conduct activities directed toward researching, discovering and developing therapeutic antisense oligonucleotides designed to bind and modulate the RNA of each collaboration target, (ii) Isis will endeavor to identify a development
        candidate for each collaboration target, and (iii) for each collaboration target for which Isis identifies a development candidate, JBI will have an exclusive option to obtain an exclusive license under this Agreement to develop, manufacture and
        commercialize Products in the Field.</font></div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt; font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;">NOW, THEREFORE</font><font style="font-size: 10pt;">, in consideration of the respective covenants, representations, warranties and
        agreements set forth herein, the Parties hereto agree as follows:</font></div>
    <div>&#160;</div>
    <div style="text-align: center; font-weight: bold;">ARTICLE 1.</div>
    <div style="text-align: center; font-weight: bold;">RESEARCH COLLABORATION</div>
    <div>&#160;</div>
    <table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">1.1</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Collaboration Overview</u></font><font style="font-size: 10pt;">.&#160; The intent of the Collaboration is: (i) for the Parties to conduct a Drug Discovery Program,
                including formulation activities, for each of the Collaboration Targets and to share their respective expertise to advance the goals set out in the Drug Discovery Plan for each such Drug Discovery Program; (ii) for Isis to generate at least
                one Development Candidate under each Drug Discovery Program; (iii) for JBI to have an Option to obtain an exclusive license to Develop and Commercialize Products under each Drug Discovery Program in the Field; and (iv) if JBI exercises the
                Option for a Drug Discovery Program, the Parties will advance the Development Candidate through IND-Enabling Toxicology Studies, and thereafter JBI will continue to Develop and Commercialize the applicable Development Candidate.&#160; The
                purpose of this <u>Section 1.1</u> is to provide a high-level overview of the roles, responsibilities, rights and obligations of each Party under this Agreement, and therefore this <u>Section 1.1</u> is qualified in its entirety by the
                more detailed provisions of this Agreement set forth below.</font></div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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      <div style="width: 100%;" id="DSPFPageHeader">Confidential</div>
    </div>
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        <tr>
          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">1.2</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Collaboration Targets</u></font><font style="font-size: 10pt;">.</font></div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">

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          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">1.2.1</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Maximum Number; Initial Collaboration Target</u></font><font style="font-size: 10pt;">.&#160; The maximum number of Collaboration Targets will be three, subject to <u>Section


                  1.2.2</u>.&#160; The Parties agree that the first Collaboration Target is [***].&#160; JBI will designate the second Collaboration Target within [***] of the Effective Date, and designate the third Collaboration Target within [***] of the Effective
                Date (each, a <font style="font-weight: bold; font-style: italic;">&#8220;Target Nomination Period&#8221;</font>), in each case in accordance with the mechanism set forth in <u>Section 1.2.3</u> below.</font></div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">

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          </td>
          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">1.2.2</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Optional Fourth Collaboration Target</u></font><font style="font-size: 10pt;">.&#160; JBI will have the right, exercisable within [***] after the Effective Date, to
                designate a fourth Collaboration Target (<font style="font-style: italic;">i.e.</font>, to increase the maximum number of Collaboration Targets by one) in accordance with the mechanism set forth in <u>Section 1.2.3</u> below upon delivery
                of written notice thereof to Isis and payment to Isis of the $[***] fee pursuant to <u>Section 6.2</u>, <font style="font-style: italic;">provided</font> if JBI exercises such right, JBI must (i) designate such fourth Collaboration Target
                within [***] after the Effective Date and (ii) JBI may extend the Drug Discovery Term, if necessary, for the time required to&#160; execute under a corresponding Drug Discovery Plan for such fourth Collaboration Target under <u>Section 1.5.2</u>.&#160;


                Any [***] shall only become due if the [***], and any [***] shall be [***], and such [***] within [***] days of [***] following the date such Drug Discovery Plan is approved.</font></div>
          </td>
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    </table>
    <div>&#160;</div>
    <table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">

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          </td>
          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">1.2.3</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Collaboration Target Designation Mechanism</u></font><font style="font-size: 10pt;">.&#160; At any time during the applicable Target Nomination Period, JBI may
                propose a gene target implicated in Autoimmune Disease of the gastro-intestinal tract for designation as a Collaboration Target by providing written notice of such gene target to Isis.&#160; Isis may reject a gene target proposed by JBI if, at
                the time of such proposal: (i) Isis believes in good faith that [***] for such target; (ii) Isis does not have the [***]; (iii) granting a license to such target would [***] to a Third Party and JBI does not [***]; (iv) [***]; (v) the
                proposed target is the subject of ***] for which Isis in good faith expects to [***] (although Isis will negotiate in good faith terms for JBI to gain access such a program); or (vi) the target is associated with [***] (each of (i) through
                (vi), a <font style="font-weight: bold; font-style: italic;">&#8220;Dispositive Rejection Condition&#8221;</font>).&#160; If a Dispositive Rejection Condition for the gene target proposed by JBI for designation as a Collaboration Target exists, Isis may
                reject the proposed gene target by providing a written notice to JBI by the [***] day following Isis&#8217; receipt of JBI&#8217;s request to designate such gene target as a Collaboration Target, in which event JBI may propose a different gene target
                for designation as a Collaboration Target using the process described above in this <u>Section 1.2.3</u>.</font></div>
          </td>
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    </table>
    <div>&#160;</div>
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          </td>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.2.4</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Collaboration Target Designation</u></font><font style="font-size: 10pt;">.&#160; A gene target proposed by JBI for designation as a Collaboration Target in
                accordance with <u>Section 1.2.3</u> above will become a &#8220;Collaboration Target&#8221; if (i) Isis provides JBI a written notice accepting such gene target as a Collaboration Target or (ii) by the [***] day following Isis&#8217; receipt of JBI&#8217;s
                request to designate such gene target as a Collaboration Target, Isis has not delivered a written notice to JBI rejecting such gene target based on a Dispositive Rejection Condition.</font></div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" id="DSPFPageBreakArea">
      <div style="text-align: center;" id="DSPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;" id="DSPFPageNumber">2</font></div>
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      <div style="width: 100%;" id="DSPFPageHeader">Confidential</div>
    </div>
    <table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">

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          </td>
          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">1.2.5</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Substitution of Gene Targets</u></font><font style="font-weight: bold; font-size: 10pt;">.&#160; </font><font style="font-size: 10pt;">At any time prior to
                completion of [***] activities for a Collaboration Target, JBI may propose, in writing, a substitute gene target to replace such Collaboration Target subject to the following conditions:</font></div>
          </td>
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    </table>
    <div>&#160;</div>
    <table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">

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          </td>
          <td style="width: 36pt; vertical-align: top;">i)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>JBI may propose up to [***] ([***]) substitute gene targets, unless JBI designates a Fourth Collaboration Target whereby, in which case JBI may then propose up to [***] ([***]) substitute gene targets;</div>
          </td>
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    </table>
    <div>&#160;</div>
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          </td>
          <td style="width: 36pt; vertical-align: top;">ii)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>JBI shall pay the Substitution Fee for each proposed substitute gene target within [***] ([***]) days of the date the substitute gene target becomes a Collaboration Target under <u>Section 1.2.4</u>; and</div>
          </td>
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    </table>
    <div>&#160;</div>
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          </td>
          <td style="width: 36pt; vertical-align: top;">iii)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>The designation mechanism of <u>Section 1.2.3</u> shall apply for proposed substitute gene targets.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <div style="text-align: justify; margin-left: 72pt;">Any gene target substituted out under this <u>Section 1.2.5</u> will no longer be a Collaboration Target.</div>
    <div>&#160;</div>
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          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.3</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Drug Discovery and Development Responsibilities</u></font><font style="font-size: 10pt;">.</font></div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">

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          </td>
          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">1.3.1</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Drug Discovery Programs</u></font><font style="font-size: 10pt;">.&#160; Subject to the terms and conditions of this Agreement, during the Drug Discovery Term, the
                Parties will jointly conduct collaborative research projects directed to the research, discovery and pre-clinical development of ASOs designed to bind to and modulate the RNA of each Collaboration Target (subject to the applicable maximum
                number of Collaboration Targets under <u>Section 1.2</u>) (each, a <font style="font-weight: bold; font-style: italic;">&#8220;Drug Discovery Program&#8221;</font>).</font></div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">

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          </td>
          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">1.3.2</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Drug Discovery Plans and Development Plans</u></font><font style="font-size: 10pt;">.</font></div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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          </td>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">(a)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>For each Drug Discovery Program, the Parties, via the JRC, will: (i) promptly (but no later than [***] days) following the designation of such Collaboration Target, approve a written plan describing the discovery, research, and
              optimization activities to be conducted by each Party to achieve [***] status and to identify a Development Candidate, plus any related research activities to support such activities; and (ii) from time to time thereafter, consider and
              approve appropriate amendments and modifications to such plan (each such plan, as so amended, a <font style="font-weight: bold; font-style: italic;">&#8220;Drug Discovery Plan&#8221;</font>).&#160; By separate agreement the Parties have agreed upon the
              initial Drug Discovery Plan for the Drug Discovery Program directed to [***].&#160; Upon JRC approval of the Drug Discovery Plan for any other Collaboration Target, or upon JRC approval of any amendment or modification to any Drug Discovery Plan,
              the JRC will attach such Drug Discovery Plan, or such amendment or modification (as applicable), to the minutes of the JRC meeting at which the same is approved.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" id="DSPFPageBreakArea">
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          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">(b)</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>For each Drug Discovery Program with respect to which JBI exercises the Option, JBI will share with Isis, via the JRC (or directly with Isis if the JRC has dissolved) (i) promptly (but no later than [***] days) following such Option
              exercise, a written plan describing the proposed Development activities to be conducted by JBI with respect to the applicable Development Candidate; and (ii) from time to time thereafter consider and make appropriate amendments and
              modifications to such plan (each such plan, as so amended, a <font style="font-weight: bold; font-style: italic;">&#8220;Development Plan&#8221;</font>).&#160; The Parties, at their respective expense, shall meet and confer regarding the activities proposed
              under the Development Plan and, to the extent there are activities required of Isis under the Development Plan, shall agree on such activities within a reasonable amount of time but not to exceed [***] days following presentation of the
              Development Plan to the JRC.&#160; The JRC will attach such Development Plan or any subsequent amendments or modifications thereto (as applicable) to the minutes of the JRC meeting at which the same is agreed and approved.&#160; Each Development Plan
              will include a description of the pre-clinical studies, and clinical studies (including study designs) to support the further Development of such Development Candidate up to completion of PoC, including [***].&#160; If the Parties agree Isis will
              conduct any activities to support the further Development of the Development Candidate, the Development Plan will include the specific activities to be performed by Isis and [***] and [***] for completion of such activities.&#160; JBI will
              continue to develop and refine each Development Plan as needed and will submit it to the JRC (or the Parties if the JRC has dissolved) for review and comment at least [***].&#160; When updating each Development Plan, JBI will [***].</div>
          </td>
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    <div>&#160;</div>
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          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">1.3.3</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Allocation of Drug Discovery and Development Responsibilities</u></font><font style="font-size: 10pt;">.&#160; Each Drug Discovery Plan and Drug Development Plan will
                specify the Party(ies) responsible for performing each activity thereunder, and each Party will use Commercially Reasonable Efforts to complete such activities; <font style="font-style: italic;">provided, however,</font> that unless
                otherwise mutually agreed by the Parties in writing each Party will use Commercially Reasonable Efforts to complete the following at each respective company&#8217;s expense unless otherwise indicated:</font></div>
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          <td style="width: 36pt; vertical-align: top; font-weight: bold;">(a)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>Isis will be responsible for [***] under each Drug Discovery Plan;</div>
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          <td style="width: 36pt; vertical-align: top; font-weight: bold;">(b)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>Except as set forth in Sections (c), (d) and (f) of this <u>Section 1.3.3,</u> Isis will be responsible for [***] and [***], in each case to the extent stated to be conducted by Isis in the applicable Drug Discovery Plan;</div>
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          <td style="width: 36pt; vertical-align: top; font-weight: bold;">(c)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>JBI will be responsible for conducting the (i) [***], and (ii) the [***] including [***], in each case to achieve [***] status and produce the Development Candidate Data Package;</div>
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          <td style="width: 36pt; vertical-align: top; font-weight: bold;">(d)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>JBI will be responsible for conducting the [***], in each case to achieve [***] status, produce the Development Candidate Data Package, and to support the further Development and Commercialization of Products.&#160; Isis will provide [***] if
              requested by JBI and JBI will pay Isis for such support at [***] and shall invoice JBI in accordance with Section 6.10;</div>
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          <td style="width: 36pt; vertical-align: top; font-weight: bold;">(e)</td>
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            <div>During the Research Term Isis will (i) [***] and (ii) [***], in each case to the extent stated to be conducted by Isis in the applicable Drug Discovery Plan;</div>
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          <td style="width: 36pt; vertical-align: top; font-weight: bold;">(f)</td>
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            <div>JBI will be responsible for conducting [***], including [***]; and</div>
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          <td style="width: 36pt; vertical-align: top; font-weight: bold;">(g)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>JBI will be responsible for conducting [***] activities for each Development Candidate, including conducting [***], <font style="font-style: italic;">except</font> Isis will be responsible for conducting the [***] of the Development
              Candidate for the first Drug Discovery Program with respect to which JBI exercises the Option (the &#8220;<font style="font-weight: bold; font-style: italic;">First Development Candidate</font>&#8221;) as specified in the applicable Development Plan.</div>
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          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.3.4</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Conduct of Drug Discovery and Development Plan Activities</u></font><font style="font-size: 10pt;">.&#160; Each Party will perform the activities for which it is
                responsible under each Drug Discovery Plan and each Development Plan in good scientific manner and in compliance with, as applicable, GLP, GCP and/or GMP, and all Applicable Laws.</font></div>
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          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">1.3.5</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Disclosure of Results</u></font><font style="font-size: 10pt;">.&#160; At least [***] Business Days prior to each regularly scheduled meeting of the JRC, each Party
                will provide to the JRC a written report (which may take the form of PowerPoint slides) for each Drug Discovery Program (i) describing the Drug Discovery Program activities performed by such Party since the date of the preceding written
                report delivered by such Party for such Drug Discovery Program and the status of each such activity as of the date of such report and (ii) summarizing the data and results of the Drug Discovery Program activities performed by such Party
                under the applicable Plan.</font></div>
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          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.3.6</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Development Candidate; Supplemental Information</u></font><font style="font-size: 10pt;">.&#160; Isis will notify JBI promptly after designating a Development
                Candidate and, together with such notice, Isis will provide JBI with the applicable Development Candidate Data Package. During the [***] period beginning on Isis&#8217; delivery of the Development Candidate Data Package to JBI, JBI may request in
                writing additional data or information regarding the Development Candidate of a type that is consistent with the information JBI examines when selecting JBI&#8217;s own development candidates for similar programs and that JBI in good faith
                determines is reasonably necessary to inform JBI&#8217;s decision of whether to exercise the Option for such Drug Discovery Program (the &#8220;<font style="font-weight: bold; font-style: italic;">Supplemental Information</font>&#8221;); <font style="font-style: italic;">provided, however,</font> that: (i) unless Isis possesses and can reasonably provide the requested data or information, JBI will be solely responsible for conducting or having conducted by Isis ([***]) the work
                necessary to generate the requested Supplemental Information and for all agreed upon fees and costs incurred by it or for its account in the performance of such work; (ii) Isis will not be required to conduct any such work unless Isis and
                JBI agree to a plan for such work and JBI agrees to pay for such work at [***] and for both (i) and (ii) shall invoice JBI in accordance with Section 6.10.</font></div>
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          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.3.7</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Records and Quality.</u></font><font style="font-weight: bold; font-size: 10pt;">&#160; </font><font style="font-size: 10pt;">Isis will maintain complete and
                accurate records of all work Isis conducts in the performance of a Drug Discovery Plan and Development Plan and all results, data, inventions and developments made in the performance of such work.&#160; Such records will be in sufficient detail
                and in good scientific manner appropriate for patent and regulatory purposes.&#160; Upon reasonable prior written notice, Isis will provide JBI the right to inspect such records, and will provide copies of all requested records, to the extent
                reasonably required for the performance of JBI&#8217;s rights and obligations under this Agreement or for JBI&#8217;s reasonable quality control purposes.&#160; Isis will cooperate in good faith with respect to the conduct of any inspections by any
                Regulatory Authority of an Isis site or a contractor&#8217;s site and facilities if such inspection concerns work being performed under a Drug Discovery Plan or Development Plan.&#160; [***].&#160; In the event that during an inspection of the Isis
                facilities, the facilities are found by a Regulatory Authority to be non-compliant with one or more GLP, GMP, GCP or current standards for pharmacovigilance practice compliance standards and such facilities are being used to conduct work
                under a Drug Discovery Plan or Development Plan, Isis will [***].&#160; If requested by JBI, Isis will allow representatives of JBI to accompany Isis as part of any audit Isis conducts of [***] for which JBI exercises its Option.</font></div>
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          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">1.3.8</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Supply of API for Drug Discovery</u></font><font style="font-size: 10pt;">.&#160; On a Drug Discovery Program-by-Drug Discovery Program basis, Isis will supply (on
                its own or through a CMO), [***], (i) the non&#8209;GMP API necessary for Isis to select up to [***] lead Compounds for each Collaboration Target to advance to [***], plus (ii) up to [***] of non&#8209;GMP API for each of the lead Compounds selected
                for each Collaboration Target to support the formulation work under the Drug Discovery Plan prior to the designation of a Development Candidate. In addition, during the Drug Discovery Term, if requested by JBI, Isis will supply [***] up to
                [***] of ASO non&#8209;GMP API Isis has in its stock as of the Effective Date to support formulation activities under the Drug Discovery Plans, the selection of such non&#8209;GMP API to be in Isis&#8217; sole discretion.&#160; If additional quantities of
                non&#8209;GLP, non&#8209;GMP API are necessary to support such Drug Discovery Program activities, then JBI will purchase such API from Isis [***] for such non&#8209;GLP, non&#8209;GMP API, where [***] and [***] and where [***].&#160; All such API provided by Isis will
                be [***] specific and [***] specific ASOs.&#160; If JBI desires API for ASOs that are specific to [***] then Isis will use Commercially Reasonable Efforts to design and supply such ASOs and JBI will pay Isis for such ASOs [***] and shall invoice
                JBI in accordance with Section 6.10.</font></div>
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          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">1.3.9</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Supply of GLP Development Candidate and Clinical Supplies by Isis</u></font><font style="font-size: 10pt;">.&#160; For the first Development Candidate for which JBI
                exercises its Option Isis will (on its own or through a CMO) supply [***] of API, not to exceed [***], to support the [***] and [***], where Isis will supply the [***] of such [***], and will, [***] supply the remainder of such [***] in
                [***] increments (or in [***] if, as a result of previous [***], the remaining material is [***]) if and when requested by JBI.&#160; For each additional Development Candidate for which JBI exercises its Option, Isis, [***], will (on its own or
                through a CMO) supply in [***] a [***] of API, not to exceed [***], to support the [***] and [***].&#160; Except for the [***] of API for the first Development Candidate for which JBI has exercised its Option, JBI will [***] for such API [***],
                of which [***] within [***] days of [***].&#160; JBI will take possession of such requested API no later than [***] days following Isis&#8217; release of such API.</font></div>
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          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">1.4</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Program Costs and Expenses</u></font><font style="font-size: 10pt;">. Except as expressly set forth below or elsewhere in this ARTICLE 1, each Party will be
                responsible for the costs and expenses incurred by it or on its behalf in the performance of the Drug Discovery Program activities for which such Party is responsible under the applicable Drug Discovery Plan and Development Plan.</font></div>
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          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">1.5</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Drug Discovery Term; Extension</u></font><font style="font-size: 10pt;">.</font></div>
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          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">1.5.1</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Drug Discovery Term</u></font><font style="font-size: 10pt;">.&#160; The term for the conduct of the Drug Discovery Programs will begin on the Effective Date and,
                subject to extension in accordance with <u>Section 1.5.2</u> and/or earlier termination of this Agreement in accordance with ARTICLE 10 hereof, will end upon the earlier of (i) such time as the Options with respect to all Drug Discovery
                Programs either have been exercised by JBI or have expired unexercised, and (ii) the [***] anniversary of the Effective Date (the <font style="font-weight: bold; font-style: italic;">&#8220;Drug Discovery Term&#8221;</font>), <font style="font-style: italic;">provided</font>&#160;<font style="font-style: italic;">however</font>, that if Isis has delivered a Development Candidate Data Package to JBI for a Drug Discovery Program prior to the [***] anniversary of the Effective Date but the
                Option Period for such Drug Discovery Program has not expired as of the [***] anniversary of the Effective Date, the Drug Discovery Term will extend for that Drug Discovery Program only, until the earlier of (a) JBI&#8217;s exercise of such
                Option and (b) expiration of such Option Period.&#160; Such extension shall not be subject to the extension fee as defined in Section 1.5.2 below.</font></div>
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          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">1.5.2</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Extension of Drug Discovery Term</u></font><font style="font-size: 10pt;">.&#160; JBI will have the right, in its discretion, to extend the Drug Discovery Term (i)
                for an additional [***] period if such extension applies to more than just the [***] Collaboration Target (not to exceed [***]), or (ii) for one additional [***] period if such extension only applies to the [***] Collaboration Target (not
                to exceed [***]), in each case by delivering a written notice of extension to Isis and paying Isis an extension payment of $[***] per extension no later than [***] days prior to the end of the then-applicable Drug Discovery Term.</font></div>
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          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">1.5.3</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Consequences of End of Drug Discovery Term</u></font><font style="font-size: 10pt;">.&#160; From and after the end of the Drug Discovery Term (including any
                extensions thereof), (i) Isis will have no obligation to perform any further activities for any Drug Discovery Program; (ii) any Drug Discovery Programs that have not reached the Development Candidate stage will no longer be Drug Discovery
                Programs and the applicable gene targets associated therewith will no longer be Collaboration Targets; (iii) Isis&#8217; obligations and JBI&#8217;s rights under this Agreement with respect to such gene target and any ASOs targeting such gene target
                will then terminate, and Isis will be free to Develop and Commercialize on its own or with a Third Party such gene target and any Compounds targeting such gene target; and (iv) Isis will own any data generated under the Drug Discovery
                Program for such gene target and any Compounds targeting such gene target.&#160; For clarity, except to the extent explicitly set forth in the foregoing, the expiration of the Drug Discovery Term will not affect either Party&#8217;s rights or
                obligations under this Agreement with respect to any Drug Discovery Program for which JBI exercised its Option before the end of the Drug Discovery Term, including, but not limited to, the Parties&#8217; respective rights and obligations under
                ARTICLE 2, ARTICLE 4, ARTICLE 5 and ARTICLE 6 hereof.</font></div>
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          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.5.4</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Carryover Development Candidates</u></font><font style="font-size: 10pt;"><u>.</u>&#160; If, despite Isis&#8217; Commercially Reasonable Efforts, by the end of the Drug
                Discovery Term, Isis has not designated a Development Candidate for a particular Drug Discovery Program, then if at any time during the [***] following the end of the Drug Discovery Term Isis&#8217; RMC designates an ASO discovered by Isis that
                is designed to bind to the RNA that encodes the Collaboration Target that was the subject of such Drug Discovery Program as a development candidate ready to start IND-Enabling Toxicology Studies (such ASO, a <font style="font-weight: bold; font-style: italic;">&#8220;Carryover Development Candidate&#8221;</font>), then, Isis will notify JBI and will provide JBI with the data package presented to Isis&#8217; RMC to approve such Carryover Development Candidate. JBI will then have [***] days
                from its receipt of such package to elect to enter into an agreement (or amendment to this Agreement) for an option and license under the same terms as set forth in this Agreement, including the payment of the fee for [***] if not already
                paid by JBI (except that no additional option fee under <u>Section</u> 6.1 will be due). If, within [***] days after JBI&#8217;s receipt of such notice from Isis, JBI provides Isis with written notice that it accepts such offer from Isis for
                such Carryover Development Candidate, the Parties will execute an agreement (or amendment to this Agreement) regarding such Carryover Development Candidate containing the same terms as those described herein.&#160; If JBI either notifies Isis
                that it declines the offer for such Carryover Development Candidate, or JBI does not provide Isis with written notice during such [***]-day period that JBI accepts such offer from Isis for such Carryover Development Candidate, then Isis
                will be free to research, develop, manufacture and commercialize such Carryover Development Candidate (and/or any other ASO designed to bind to the RNA that encodes the gene target targeted by such Carryover Development Candidate) by itself
                or with or for a Third Party.</font></div>
          </td>
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          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">1.6</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Program Management</u></font><font style="font-size: 10pt;">.</font></div>
          </td>
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    <div>&#160;</div>
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          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">1.6.1</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>JRC</u></font><font style="font-size: 10pt;">.&#160; The Parties will establish a joint research committee (the &#8220;<font style="font-weight: bold; font-style: italic;">JRC</font>&#8221;)



                to provide advice and make recommendations on the conduct of activities under each Drug Discovery Program.&#160; The JRC will consist of three representatives appointed by Isis and three representatives appointed by JBI.&#160; Each JRC member will be
                a senior scientific staff leader or have other experience and expertise appropriate for the stage of development of the Drug Discovery Programs.&#160; Each Party will designate one of its two representatives who is empowered by such Party to
                make decisions related to the performance of such Party&#8217;s obligations under this Agreement to act as the co-chair of the JRC.&#160; The co-chairs will be responsible for overseeing the activities of the JRC consistent with the responsibilities
                set forth in <u>Section 1.6.2</u>.&#160; <font style="font-variant: small-caps;"><u>Schedule </u></font><u>1.6.1</u> sets forth certain JRC governance matters agreed to as of the Effective Date.&#160; The JRC will determine the JRC operating
                procedures at its first meeting, including the JRC&#8217;s policies for replacement of JRC members, policies for participation by additional representatives or consultants invited to attend JRC meetings, and the location of meetings, which will
                be codified in the written minutes of the first JRC meeting.&#160; Each Party will be responsible for the costs and expenses of its own employees or consultants attending JRC meetings.</font></div>
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          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">1.6.2</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Role of the JRC</u></font><font style="font-size: 10pt;">.&#160; Without limiting any of the foregoing, subject to <u>Section 1.6.3</u>, the JRC will perform the
                following functions, some or all of which may be addressed directly at any given JRC meeting:</font></div>
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          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">(a)</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>maintain the list of Collaboration Targets, as such list may be updated from time to time in accordance with this Agreement, and attach such list to the minutes of the next JRC meeting following the designation of any additional
              Collaboration Target;</div>
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          <td style="width: 36pt; vertical-align: top; font-weight: bold;">(b)</td>
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            <div>review and approve the Drug Discovery Plan for each Program;</div>
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          <td style="width: 36pt; vertical-align: top; font-weight: bold;">(c)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>review the overall progress of the Parties&#8217; efforts to achieve [***] with respect to each Drug Discovery Program;</div>
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          <td style="width: 36pt; vertical-align: top; font-weight: bold;">(d)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>review the overall progress of Isis&#8217; efforts to discover, identify, optimize and select the Development Candidate for each Drug Discovery Program;</div>
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          <td style="width: 36pt; vertical-align: top; font-weight: bold;">(e)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>review the overall progress of the Parties&#8217; efforts with respect to each the Drug Discovery Plan;</div>
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          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">(f)</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>amend each Drug Discovery Plan for each Drug Discovery Program,</div>
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          <td style="width: 36pt; vertical-align: top; font-weight: bold;">(g)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>such other review and advisory responsibilities as may be assigned to the JRC pursuant to this Agreement.</div>
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          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">1.6.3</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Decision Making</u></font><font style="font-size: 10pt;">.&#160; Each Party will give due consideration to, and consider in good faith, the recommendations and advice
                of the JRC regarding the conduct of each Drug Discovery Program.&#160; Subject to <u>Section 1.3.1</u> and <u>Section 1.3.5</u>, (i) Isis will have the final decision-making authority regarding [***] and whether to accept and how to implement
                the JRC&#8217;s recommendations, and (ii) JBI will have the final decision-making authority regarding [***]; <font style="font-style: italic;">provided that,</font> in each case, such decisions and conduct are in accordance with the applicable
                Drug Discovery Plan and do not increase the cost of the other Party.&#160; Except as otherwise permitted by <u>Section 1.3.2,</u>&#160;<u>Section 1.3.5</u> and, the JRC will have no decision making authority and will act as a forum for sharing
                information about the activities conducted by the Parties hereunder and as an advisory body, in each case only on the matters described in, and to the extent set forth in, this Agreement.</font></div>
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          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.6.4</td>
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            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Term of the JRC</u></font><font style="font-size: 10pt;">.&#160; Isis&#8217; obligation to participate in the JRC, or any of its subcommittees, will terminate upon JBI&#8217;s
                exercise (or expiration) of the Option for the last Drug Discovery Program.</font></div>
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          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">1.6.5</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Alliance Managers</u></font><font style="font-size: 10pt;">.&#160; Each Party will appoint a representative to act as its alliance manager under this Agreement (each,
                an &#8220;<font style="font-weight: bold; font-style: italic;">Alliance Manager</font>&#8221;).&#160; Each Alliance Manager will be responsible for supporting the JRC and performing the activities listed in <font style="font-variant: small-caps;"><u>Schedule


                  </u></font><u>1.6.5</u>.</font></div>
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          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.6.6</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Information Sharing Committee</u></font><font style="font-weight: bold; font-size: 10pt;">.&#160; </font><font style="font-size: 10pt;">Formation and Purpose: Within
                [***] days after the [***], the Parties will establish an Information Sharing Committee (the &#8220;ISC&#8221;) to review the Development of Product.&#160; The ISC will review and discuss the Development activities to be undertaken with respect to the
                Product being Developed by JBI and will provide a forum for Isis to provide input into such Development activities.&#160; Specific Responsibilities of the ISC:&#160; As part of its overall responsibilities, the ISC will: review the progress of the
                Development Plan; review any changes to the Development Plan; actively seek Isis input and consider all input in good faith; and perform such other functions as appropriate to further the purposes of this Agreement as determined by the
                Parties</font></div>
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          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.6.7</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>ISC Meetings</u></font><font style="font-size: 10pt;">: The ISC will meet at least annually or on an <font style="font-style: italic;">ad hoc </font>basis.&#160;
                The first meeting of the ISC will be held as soon as reasonably practicable, but in no event later than [***] days after formation.&#160; Meetings will be held at such place or places as are mutually agreed or by teleconference or
                videoconference.&#160; The ISC&#160; meetings will be chaired by JBI.&#160; The chairperson of the ISC will be responsible for calling meetings, preparing and circulating an agenda in advance of each meeting of the ISC, and preparing and issuing minutes
                of each meeting within [***] days thereafter; <u>provided however</u>, that an ISC chairperson will call a meeting promptly upon the request by Isis to convene an ISC meeting.&#160; The minutes will not be finalized until both Parties review
                and approve them.&#160; Each Party will bear its own costs, including travel expenses, incurred by its ISC members or by any additional non-member participants of a Party in connection with their attendance at ISC meetings and other activities
                related to any ISC.&#160; Notwithstanding <u>Section 1.6.6</u> and the foregoing provisions of this <u>Section 1.6.7</u>, with respect to Isis, the formation of the ISC and participation in the ISC are rights but not obligations that Isis may
                cancel for any Product at any time.</font></div>
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          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.6.8</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Reduction of ISC Reporting</u></font><font style="font-size: 10pt;">.&#160; If JBI declines to pursue any Follow-On Compounds targeting a particular Collaboration
                Target and Isis pursues a Follow-On Compound for such Collaboration Target, the ISC shall cease all ISC reporting activities relating to Products that modulate such Collaboration Target.</font></div>
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          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.7</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Materials Transfer.</u></font><font style="font-size: 10pt;"> To facilitate the activities under the Drug Discovery Programs, either Party may provide certain
                materials for use by the other Party. All such materials will be used by the receiving Party in accordance with terms of this Agreement solely for purposes of exercising its rights and performing its obligations under this Agreement, and
                the receiving Party will not transfer such materials to any Third Party except with the written consent of the supplying Party. Except as expressly set forth herein, THE MATERIALS ARE PROVIDED &#8220;AS IS&#8221; AND WITHOUT ANY REPRESENTATION OR
                WARRANTY, EXPRESS OR IMPLIED, INCLUDING ANY IMPLIED WARRANTY OF MERCHANTABILITY OR OF FITNESS FOR ANY PARTICULAR PURPOSE OR ANY WARRANTY THAT THE USE OF THE MATERIALS WILL NOT INFRINGE OR VIOLATE ANY PATENT OR OTHER PROPRIETARY RIGHTS OF
                ANY THIRD PARTY.</font></div>
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    </div>
    <div style="text-align: center; font-weight: bold;">ARTICLE 2.</div>
    <div style="text-align: center; font-weight: bold;">EXCLUSIVITY COVENANTS</div>
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          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">2.1</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Exclusivity; Right of First Negotiation</u></font><font style="font-size: 10pt;">.</font></div>
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          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">2.1.1</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Exclusivity Covenants</u></font><font style="font-size: 10pt;">.</font></div>
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          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">(a)</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>The Parties&#8217; Exclusivity Covenants for Collaboration Targets During the Option Period</u></font><font style="font-size: 10pt;">.&#160; On a Collaboration
                Target-by-Collaboration Target basis, each Party agrees that, except in the performance of its obligations under this Agreement and except as set forth in <u>Section 2.1.2</u>, <u>Section 2.1.3</u>, <u>Section 10.3.2</u> or <u>Section
                  10.3.4</u>, it will not work independently or for or with any of its Affiliates or any Third Party (including the grant of any license to any Third Party) with respect to discovery, research, development, manufacture or commercialization
                of an ASO that is designed to bind to the RNA that encodes such Collaboration Target in the Field from the Effective Date through the expiration of the applicable Option Period or the earlier termination of the applicable Option.</font></div>
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          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">(b)</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Isis&#8217; Exclusivity Covenant After Option Exercise</u></font><font style="font-size: 10pt;">.&#160; On a Collaboration Target-by-Collaboration Target basis, except as
                set forth in <u>Section 2.1.2</u>, <u>Section 2.1.3</u>, <u>Section 10.3.2</u> or <u>Section 10.3.4</u>, if JBI exercises the Option in accordance with this Agreement, then Isis will not work independently or for or with any of its
                Affiliates or any Third Party (including the grant of any license to any Third Party) with respect to:</font></div>
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          <td style="width: 36pt; vertical-align: top; font-weight: bold;">(i)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>discovery, research or development of an ASO that is designed to bind to the RNA that encodes such Collaboration Target in the Field until [***] for a Product targeting such Collaboration Target; and</div>
          </td>
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    <div>&#160;</div>
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          </td>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">(ii)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>on a country-by-country basis, commercializing an ASO that is designed to bind to the RNA that encodes such Collaboration Target in the Field until [***] with respect to such Collaboration Target.</div>
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    <div>&#160;</div>
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          <td style="width: 36pt; vertical-align: top; font-weight: bold;">(c)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>JBI&#8217;s Exclusivity Covenant After Option Exercise</u></font><font style="font-size: 10pt;">.&#160; After Option exercise, JBI&#8217;s exclusivity obligations under <u>Section


                  2.1.1(a)</u> will be extended and will continue for so long as and to the extent of Isis&#8217; exclusivity obligations under <u>Section 2.1.1(b), and except as otherwise described in Section 2.1.3</u>.</font></div>
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    <div>&#160;</div>
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          </td>
          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">2.1.2</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Right of First Negotiation for Follow-On Compounds</u></font><font style="font-size: 10pt;">.&#160; On a Drug Discovery Program-by-Drug Discovery Program basis,
                during the period commencing on the date JBI exercises the applicable Option in accordance with this Agreement and ending upon [***] (such period, the &#8220;<font style="font-weight: bold; font-style: italic;">ROFN Period</font>&#8221;), Isis hereby
                grants to JBI a right of first negotiation to develop and commercialize any Follow-On Compound developed by or on behalf of Isis, which right of first negotiation is granted on the following terms and conditions:</font></div>
          </td>
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    </table>
    <div>&#160;</div>
    <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" id="DSPFPageBreakArea">
      <div style="text-align: center;" id="DSPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;" id="DSPFPageNumber">11</font></div>
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    </div>
    <table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">

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          </td>
          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">(a)</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>At any time prior to the [***] following the [***] for the applicable Product, JBI may provide Isis with a non-binding, good faith written notice expressing JBI&#8217;s desire for Isis to identify a Follow-On Compound (a &#8220;<font style="font-weight: bold; font-style: italic;">Follow-On Interest Notice</font>&#8221;).&#160; If (i) JBI does not provide Isis with a Follow-On Interest Notice before the [***] following the [***] for the applicable Product, or (ii) JBI does timely
              provide Isis with a Follow-On Interest Notice but the Parties do not agree on a [***] related to such Follow-On Compound by 5:00 pm (Eastern Time) on the [***] following the [***] for the applicable Product, then, Isis may work independently
              or with any of its Affiliates or any Third Party with respect to the discovery, research, development and manufacture of a Follow-On Compound; <font style="font-style: italic;">provided, however</font>, that during [***], Isis will not grant
              any license (or an option to obtain such a license) under any intellectual property owned, controlled or licensed by Isis to make, use or sell any Follow-On Compound (a &#8220;<font style="font-weight: bold; font-style: italic;">Follow-On Agreement</font>&#8221;)

              <font style="font-style: italic;"><u>unless and until</u></font> Isis provides a written notice to JBI (a &#8220;<font style="font-weight: bold; font-style: italic;">Follow-On Negotiation Notice</font>&#8221;), which notice [***].&#160; Isis will not enter
              into such a Follow-On Agreement with any Third Party until the earlier to occur of: (A) [***] (each, a &#8220;<font style="font-weight: bold; font-style: italic;">ROFN Termination Event</font>&#8221;).</div>
          </td>
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    </table>
    <div>&#160;</div>
    <table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">

        <tr>
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          </td>
          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">(b)</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>Following a ROFN Termination Event, subject to JBI&#8217;s right under <u>Section 1.6.8</u> to stop sharing information, Isis will have no further obligation to negotiate with JBI or its Affiliates with respect to such Follow-On Agreement, and
              Isis will be free to negotiate and enter an agreement with a Third Party with respect to a Follow-On Agreement.&#160; Any Follow-On Agreement entered into by Isis with a Third Party in accordance with this <u>Section 2.1.2(b)</u> will be a
              Permitted License to the extent related to the Follow-On Compound.</div>
          </td>
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    <div>&#160;</div>
    <table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">

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          </td>
          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">2.1.3</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Limitations and Exceptions to Exclusivity Covenants</u></font><font style="font-size: 10pt;">.&#160; Notwithstanding anything to the contrary in this Agreement, each
                Party&#8217;s practice of the following will not violate <u>Section 2.1.1</u> and/or <u>Section 2.1.2</u>:</font></div>
          </td>
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    </table>
    <div>&#160;</div>
    <table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">

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          <td style="width: 63pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">(a)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>Any activities conducted pursuant to the Prior Agreements as in effect on the Effective Date; <u>provided</u>, [***];</div>
          </td>
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    </table>
    <div>&#160;</div>
    <table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">

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          <td style="width: 63pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">(b)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>The granting by Isis of, or performance of obligations under, Permitted Licenses;</div>
          </td>
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    </table>
    <div>&#160;</div>
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          </td>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">(c)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>Up to and including the date of the [one year anniversary following the Option Period for a designated Collaboration Target, JBI may acquire, by license or otherwise, any Third Party asset that modulates a Collaboration Target so long as
              such Third Party asset has at least entered a Phase II Clinical Trial at the time of such acquisition; and</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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      <div style="text-align: center;" id="DSPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;" id="DSPFPageNumber">12</font></div>
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          <td style="width: 36pt; vertical-align: top; font-weight: bold;">(d)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>After the date of the [***] for a designated Collaboration Target, JBI may [***], any Third Party [***] so long as such Third Party [***].</div>
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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 style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Effect of Exclusivity on Indications</u></font><font style="font-size: 10pt;">.&#160; The Compounds are designed to bind to the RNA that encodes a Collaboration
                Target in the Field with the intent of treating Autoimmune Diseases of the gut.&#160; Isis and JBI are subject to exclusivity obligations under <u>Section 2.1</u>; <font style="font-style: italic;">however</font>, the Parties acknowledge and
                agree that each Party (on its own or with a Third Party) may continue to discover, research, develop, manufacture and commercialize products that are designed to bind to the RNA that encodes any gene that is <font style="font-style: italic;"><u>not</u></font> a Collaboration Target for any indication, even if such products are designed to treat Autoimmune Disease.</font></div>
          </td>
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    </table>
    <div>&#160;</div>
    <div style="text-align: center; font-weight: bold;">ARTICLE 3.</div>
    <div style="text-align: center; font-weight: bold;">EXCLUSIVE OPTION</div>
    <div>&#160;</div>
    <table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">

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          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">3.1</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Option Grant and Option Deadline</u></font><font style="font-size: 10pt;">.&#160; On a Drug Discovery Program-by-Drug Discovery Program basis, Isis hereby grants to
                JBI with respect to each Drug Discovery Program an exclusive option to obtain the license set forth in <u>Section 4.1.1</u> with respect to such Drug Discovery Program (each an &#8220;<font style="font-weight: bold; font-style: italic;">Option</font>&#8221;).&#160;



                JBI (i) shall provide Isis with written notice of its intent to exercise its Option within [***] days of receipt of the Development Candidate package for the application Drug Discovery Program and (ii) JBI shall pay the Option Fee described
                in Section 6.4 no later than the [***] day following JBI&#8217;s notice of its intent to exercise its Option (the &#8220;<font style="font-weight: bold; font-style: italic;">Option Deadline</font>&#8221;).</font></div>
          </td>
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    </table>
    <div>&#160;</div>
    <table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">

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          <td style="width: 36pt; vertical-align: top; font-weight: bold;">3.2</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Effect of Option Exercise or Expiration</u></font><font style="font-size: 10pt;">.&#160; If, by the Option Deadline, JBI or its designated Affiliate (i) notifies Isis
                in writing that it wishes to exercise the applicable Option, and (ii) pays to Isis the license fee set forth in <u>Section 6.4</u>, Isis will, and hereby does, grant to JBI or its designated Affiliate the license set forth in <u>Section
                  4.1.1</u>.&#160; If, by the applicable Option Deadline, JBI or its designated Affiliate has not both (y) provided Isis a written notice stating that JBI is exercising its Option, and (z) paid Isis the license fee in accordance with <u>Section
                  6.4</u>, then JBI&#8217;s Option for the applicable Drug Discovery Program will expire.</font></div>
          </td>
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    </table>
    <div>&#160;</div>
    <div style="text-align: center; font-weight: bold;">ARTICLE 4.</div>
    <div style="text-align: center; font-weight: bold;">LICENSE GRANTS</div>
    <div>&#160;</div>
    <table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">4.1</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>License Grants to JBI</u></font><font style="font-size: 10pt;">.</font></div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">4.1.1</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Development and Commercialization License</u></font><font style="font-size: 10pt;">.&#160; Subject to the terms and conditions of this Agreement, on a Drug Discovery
                Program-by-Drug Discovery Program basis, effective upon JBI&#8217;s exercise of the Option for a particular Drug Discovery Program in accordance with this Agreement, Isis grants to JBI (i) a worldwide, exclusive, royalty-bearing, sublicensable
                (in accordance with <u>Section 4.1.2</u> below) license under the Isis Product Specific Patents to Research, Develop, Manufacture, have Manufactured (in accordance with <u>Section 4.1.2</u> below), register, market and Commercialize
                Products under such Drug Discovery Program in the Field, and (ii) a worldwide, exclusive, royalty-bearing, sublicensable (in accordance with <u>Section 4.1.2</u> below) license under the Licensed Technology other than the Isis Product
                Specific Patents to Research, Develop, Manufacture, have Manufactured (in accordance with <u>Section 4.1.2</u> below), register, market and Commercialize Products under such Drug Discovery Program in the Field.&#160; The grant described in
                subsection (ii) in no way limits Isis&#8217; ability to grant additional licenses to Third Parties under the Licensed Technology, other than the Isis Product Specific Patents, to Research, Develop, Manufacture, have Manufactured register, market
                and Commercialize Third Party products that are not Product(s).</font></div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" id="DSPFPageBreakArea">
      <div style="text-align: center;" id="DSPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;" id="DSPFPageNumber">13</font></div>
      <div style="page-break-after: always;" id="DSPFPageBreak">
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          </td>
          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">4.1.2</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Sublicense Rights; CMO Licenses</u></font><font style="font-size: 10pt;">.</font></div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">

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          </td>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">(a)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>Subject to the terms and conditions of this Agreement, JBI will have the right to grant sublicenses under the license granted under <u>Section 4.1.1</u> above:</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">

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          </td>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">(i)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>under the Isis Core Technology Patents, Isis Product-Specific Patents, Isis Formulation Patents and Isis Know-How, to an Affiliate of JBI or a Third Party; and</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">

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          </td>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">(ii)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>under the Isis Manufacturing and Analytical Patents and Isis Manufacturing and Analytical Know-How, solely to (y) [***] or (z) [***];</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <div style="text-align: justify; margin-left: 108pt; font-size: 12pt;"><font style="font-style: italic; font-size: 10pt;">provided that</font><font style="font-size: 10pt;"> each such sublicense will be subject to, and consistent with, the terms and
        conditions of this Agreement.&#160; If, within 90 days of first learning of any breach of such sublicense terms, JBI fails to take any action to enforce the sublicense terms of a sublicense granted pursuant to this <u>Section 4.1.2</u>, which failure
        would cause an adverse effect on Isis, JBI hereby grants Isis the right to enforce such sublicense terms on JBI&#8217;s behalf and will cooperate with Isis (which cooperation will be at JBI&#8217;s sole expense and will include, JBI joining any action before a
        court or administrative body filed by Isis against such Sublicensee if and to the extent necessary for Isis to have legal standing before such court or administrative body)<font style="font-weight: bold;">&#160;</font>in connection with enforcing such
        terms.&#160; JBI will provide Isis with a true and complete copy of any sublicense granted pursuant to this <u>Section 4.1.2</u> within [***] days after the execution thereof.</font></div>
    <div>&#160;</div>
    <table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">

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          </td>
          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">(b)</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>In connection with [***], or supply API and Finished Drug Product for Commercialization, Isis will, at JBI&#8217;s option, either (1) [***], which Isis agrees it will [***], or, (2) permit JBI to [***].&#160; Each such manufacturing agreement between
              JBI and [***] will contain provisions permitting Isis to elect to have such agreements assigned to Isis to the extent such agreement relates to the applicable Clinical Supplies or Finished Drug Product in the event of a termination of this
              Agreement with respect to a particular Drug Discovery Program.&#160; JBI will provide Isis with a true and complete copy of any manufacturing agreement entered into with [***] within [***] days after the execution thereof.&#160; Notwithstanding the
              foregoing, if Isis fails to comply with the terms of this <u>Section 4.1.2(b)</u> and does not cure such failure within [***] days after written notice from JBI specifying the details of any such failure, JBI will have the right to grant a
              sublicense under the Isis Manufacturing and Analytical Patents and Isis Manufacturing and Analytical Know-How to [***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" id="DSPFPageBreakArea">
      <div style="text-align: center;" id="DSPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;" id="DSPFPageNumber">14</font></div>
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          </td>
          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">(c)</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Effect of Termination on Sublicenses</u></font><font style="font-size: 10pt;">.&#160; If this Agreement terminates for any reason, any Sublicensee will, from the
                effective date of such termination, automatically become a direct licensee of Isis with respect to the rights sublicensed to the Sublicensee by JBI; <font style="font-style: italic;">so long as</font> (i) such Sublicensee is not in breach
                of its sublicense agreement, (ii) such Sublicensee agrees in writing to comply with all of the terms of this Agreement to the extent applicable to the rights originally sublicensed to it by JBI, and (iii) such Sublicensee agrees to pay
                directly to Isis such Sublicensee&#8217;s payments under this Agreement to the extent applicable to the rights sublicensed to it by JBI.&#160; JBI agrees that it will confirm clause (i) of the foregoing in writing at the request and for the benefit of
                Isis and if requested, the Sublicensee.</font></div>
          </td>
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    <div>&#160;</div>
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          </td>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">4.1.3</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>No Implied Licenses</u></font><font style="font-size: 10pt;">.&#160; All rights in and to Licensed Technology not expressly licensed to JBI under this Agreement are
                hereby retained by Isis or its Affiliates.&#160; All rights in and to JBI Technology not expressly licensed or assigned to Isis under this Agreement, are hereby retained by JBI or its Affiliates.&#160; Except as expressly provided in this Agreement,
                no Party will be deemed by estoppel or implication to have granted the other Party any license or other right with respect to any intellectual property.</font></div>
          </td>
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    </table>
    <div>&#160;</div>
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          </td>
          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">4.1.4</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>License Conditions; Limitations</u></font><font style="font-size: 10pt;">.&#160; Subject to <u>Section 6.9</u>, any license granted under <u>Section 4.1.1</u> and
                the sublicense rights under <u>Section 4.1.2</u> are subject to and limited by (i) any applicable Third Party Obligations, (ii) the Prior Agreements, and (iii) the Isis In-License Agreements, in each case to the extent the provisions of
                such obligations or agreements are specifically disclosed to JBI in writing (or via electronic data room) prior to JBI&#8217;s exercise of the applicable Option.&#160; Isis will disclose to JBI any Third Party Obligations Isis believes apply to
                applicable Products each time [***], and JBI will have the right to elect to exclude any Third Party Patent Rights and Know-How to which such Third Party Obligations apply by providing Isis written notice prior to Option exercise.&#160; If,
                prior to an Option exercise, JBI provides Isis with such a written notice to exclude certain Third Party Patent Rights and Know-How, such Third Party Patent Rights and Know-How will not be included in the Licensed Technology licensed with
                respect to the applicable Products under this Agreement.&#160; If JBI does not provide Isis with such a written notice to exclude such Third Party Patent Rights and Know-How prior to an Option exercise, such Third Party Patent Rights and
                Know-How (and any Third Party Obligations to the extent applicable to Products) will be included in the Licensed Technology licensed with respect to the applicable Products under this Agreement.</font></div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">

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          </td>
          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">4.1.5</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Trademarks for Products</u></font><font style="font-size: 10pt;">.&#160; JBI or its designated Affiliate will be solely responsible for developing, selecting,
                searching, registering and maintaining, and, subject to <u>Section 10.3</u>, will be the exclusive owner of, all trademarks, trade dress, logos, slogans, designs, copyrights and domain names used on or in connection with Products.</font></div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" id="DSPFPageBreakArea">
      <div style="text-align: center;" id="DSPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;" id="DSPFPageNumber">15</font></div>
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    </div>
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          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">4.2</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Assignment of Isis Product-Specific Patents; Grant Back to Isis</u></font><font style="font-size: 10pt;">.</font></div>
          </td>
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    </table>
    <div>&#160;</div>
    <table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">

        <tr>
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          </td>
          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">4.2.1</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>After JBI has (a) exercised its Option for a particular Product and obtained the license under <u>Section 4.1.1</u>, and (b) [***], then following review and consideration by each Party&#8217;s patent representatives, Isis will assign to JBI or
              one or more of its designated Affiliates, Isis&#8217; ownership interest in (i) all Isis Product-Specific Patents related to such Product in the Field that are owned by Isis (whether solely owned or jointly owned with one or more Third Parties),
              and (ii) any Jointly-Owned Program Patents Covering such Product, and thereafter, subject to <u>Section 7.2.4</u>, Isis will have no further right to control any aspect of the Prosecution and Maintenance of such Isis Product Specific Patents
              and such Jointly-Owned Program Patents.&#160; The assignment of Patent Rights assigned in this <u>Section 4.2.1</u> will occur within 30 days of JBI paying Isis the milestone for Completion of a PoC for the applicable Product.</div>
          </td>
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    </table>
    <div>&#160;</div>
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          </td>
          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">4.2.2</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>JBI grants to Isis a fully-paid, royalty-free, worldwide, exclusive, sublicensable license under any Isis Product Specific Patents and Jointly-Owned Program Patents assigned to JBI under <u>Section 4.2.1</u>, (i) [***], (ii) to [***] and
              (iii) to [***] to the extent permitted by this Agreement.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">4.3</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Subcontracting</u></font><font style="font-size: 10pt;">.&#160; Subject to the terms of this <u>Section 4.3</u>, each Party will have the right to engage Third-Party
                subcontractors to perform certain of its obligations under this Agreement.&#160; Any subcontractor to be engaged by a Party to perform a Party&#8217;s obligations set forth in the Agreement will meet the qualifications typically required by such Party
                for the performance of work similar in scope and complexity to the subcontracted activity and will enter into such Party&#8217;s standard nondisclosure agreement consistent with such Party&#8217;s standard practices.&#160; Any Party engaging a subcontractor
                hereunder will remain responsible and obligated for such activities and will not grant rights to such subcontractor that interfere with the rights of the other Party under this Agreement.</font></div>
          </td>
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    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">4.4</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Technology Transfer after Option Exercise</u></font><font style="font-size: 10pt;">.&#160; On a Drug Discovery Program-by-Drug Discovery Program basis, Isis will
                promptly, but no later than [***] days after JBI exercises its Option for such Drug Discovery Program hereunder, deliver to JBI or one or more designated Affiliates:</font></div>
          </td>
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    </table>
    <div>&#160;</div>
    <table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">

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          </td>
          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">4.4.1</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Isis Know-How</u></font><font style="font-size: 10pt;">.&#160; All Isis Know-How in Isis&#8217; possession that has not previously been provided hereunder, for use solely
                in accordance with the licenses granted under <u>Section 4.1.1</u> and <u>Section 10.3.2</u>, including transferring the IND for the applicable Development Candidate to JBI together with all regulatory documentation (including drafts)
                related to the applicable Development Candidate.</font></div>
          </td>
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    </table>
    <div>&#160;</div>
    <table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">

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          </td>
          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">4.4.2</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Isis Manufacturing and Analytical Know-How</u></font><font style="font-size: 10pt;">.&#160; Solely for use by JBI, its Affiliates or a Third Party acting on JBI&#8217;s
                behalf to Manufacture API in JBI&#8217;s own or an Affiliate&#8217;s manufacturing facility, all Isis Manufacturing and Analytical Know-How in Isis&#8217; Control relating to applicable Products, which is necessary for the exercise by JBI, its Affiliates or
                a Third Party of the Manufacturing rights granted under <u>Section 4.1.1</u>, in each case solely to Manufacture API, Clinical Supplies or Finished Drug Product in accordance with the terms of this Agreement.</font></div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" id="DSPFPageBreakArea">
      <div style="text-align: center;" id="DSPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;" id="DSPFPageNumber">16</font></div>
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    </div>
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          </td>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">4.4.3</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Isis Contribution of FTEs for Know-How Transfer.</u></font><font style="font-size: 10pt;">&#160; Isis will provide up to [***] hours of its time [***] to JBI for each
                Drug Discovery Program to transfer such Isis Know-How and Manufacturing and Analytical Know-How under <u>Section 4.4.1</u> and <u>Section 4.4.2.</u> Thereafter, if requested by JBI, Isis will provide JBI with a reasonable level of
                assistance in connection with such transfer, which JBI will reimburse Isis for its time incurred in providing such assistance at [***] incurred by Isis in providing such assistance and shall invoice JBI in accordance with Section 6.10.</font></div>
          </td>
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    </table>
    <div>&#160;</div>
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          </td>
          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">4.4.4</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>API and Product</u></font><font style="font-size: 10pt;">.&#160; Upon JBI&#8217;s written request, Isis will sell to JBI any bulk API in Isis&#8217; possession at the time of
                Option exercise, at a price equal to [***].</font></div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <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 style="font-weight: bold;"><u>Cross-Licenses Under Program Technology.</u></div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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          </td>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">4.5.1</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Enabling Patent Licenses from JBI to Isis.</u></font><font style="font-size: 10pt;">&#160; Subject to the terms and conditions of this Agreement (including Isis&#8217;
                exclusivity obligations under <u>Section 2.1.1</u>), JBI hereby grants Isis a fully-paid, royalty-free, irrevocable, worldwide, non-exclusive, sublicenseable license under any JBI Program Technology to research, develop, manufacture, have
                manufactured and commercialize [***].</font></div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">

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          </td>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">4.5.2</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Enabling Patent Licenses from Isis to JBI.</u></font><font style="font-size: 10pt;">&#160; Subject to the terms and conditions of this Agreement (including JBI&#8217;s
                exclusivity obligations under <u>Section 2.1.1</u>), Isis hereby grants JBI a fully-paid, royalty-free, irrevocable, worldwide, non-exclusive, sublicenseable license under any Isis Program Technology to research, develop, manufacture, have
                manufactured and commercialize [***].</font></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;">DEVELOPMENT, MANUFACTURING AND COMMERCIALIZATION</div>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">5.1</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>JBI Diligence</u></font><font style="font-size: 10pt;">.&#160; Following an Option exercise, JBI will be solely responsible for all Development, Manufacturing and
                Commercialization activities, and for all costs and expenses associated therewith, with respect to the Development, Manufacture and Commercialization of applicable Products; and JBI will use Commercially Reasonable Efforts to Develop,
                Manufacture and Commercialize in each and every Major Market at least one Product from each Drug Discovery Program for which an Option has been exercised.</font></div>
          </td>
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    <div>&#160;</div>
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          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">5.2</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Specific Performance Milestone Events</u></font><font style="font-size: 10pt;">.&#160; Without limiting any of the foregoing, following an Option exercise, JBI will
                use Commercially Reasonable Efforts to achieve the specific performance milestone events set forth in <font style="font-variant: small-caps;"><u>Schedule </u></font><u>5.2</u> (&#8220;<font style="font-weight: bold; font-style: italic;">Specific


                  Performance Milestone Events</font>&#8221;) for a Product on the timeline set forth in <font style="font-variant: small-caps;"><u>Schedule </u></font><u>5.2</u>; <font style="font-style: italic;">provided, however</font>, if [***].</font></div>
          </td>
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    </table>
    <div>&#160;</div>
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      <div style="text-align: center;" id="DSPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;" id="DSPFPageNumber">17</font></div>
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      <div style="width: 100%;" id="DSPFPageHeader">Confidential</div>
    </div>
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        <tr>
          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">5.3</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Integrated Development Plan</u></font><font style="font-size: 10pt;">.&#160; On a Product-by-Product basis, JBI will prepare a Development and global integrated
                Development plan outlining key aspects of the Development of each Product through Approval (each, an &#8220;<font style="font-weight: bold; font-style: italic;">Integrated Development Plan</font>&#8221; or &#8220;<font style="font-weight: bold; font-style: italic;">IDP</font>&#8221;).&#160; JBI will prepare the IDP no later than [***] after [***], and the IDP will contain information consistent with JBI&#8217;s Development plans for its similar products at similar stages of development.&#160; Once JBI has
                prepared such plans, JBI will update the IDP consistent with JBI&#8217;s standard practice and provide such updates to Isis annually via the ISC.</font></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;">5.4</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Regulatory</u></font><font style="font-size: 10pt;">.</font></div>
          </td>
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    <div>&#160;</div>
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          </td>
          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">5.4.1</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Ownership of and Assistance with Regulatory Filings</u></font><font style="font-size: 10pt;">.</font></div>
          </td>
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    <div>&#160;</div>
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          </td>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">(a)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>For each Product for which JBI has exercised its Option, JBI will be the sponsor and will be responsible for filing the IND.&#160; Once a Development Candidate is designated under this Agreement, the JRC will work to establish a plan for IND
              filing support and activities, which plan will include a timeline and responsibilities for filing the IND.</div>
          </td>
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          </td>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">(b)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>[***] begin to prepare a plan, for drafting and reviewing the sections of the NDA and MAA for the applicable Product (including establishing responsibilities for drafting and reviewing common technical document (&#8220;<font style="font-weight: bold; font-style: italic;">CTD</font>&#8221;) modules, authorship, plan activity timelines and associated costs and expenses).&#160; The Parties will act in good faith and mutually agree upon each such plan, <font style="font-style: italic;">provided,

                however</font>, that, after exercising an Option for the applicable Drug Discovery Program, JBI will have final decision making authority with respect to the contents of such plan that do not require Isis&#8217; participation.</div>
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          <td style="width: 63pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">(c)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>[***] regulatory filings for the Product, [***] and JBI, including [***] plus any reasonable ***] providing such assistance and will specify that JBI will [***] designated responsibilities in connection with the applicable regulatory
              filing [***] in accordance with Section [***]; provided there will be no additional ***] conducted under a Development Plan where [***].</div>
          </td>
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          </td>
          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">5.4.2</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>[</u></font><font style="font-size: 10pt;"><u>***</u><font style="font-weight: bold;"><u>] Meetings with FDA</u></font>.&#160; For each Product, JBI shall [***]
                meetings with the FDA to discuss (i) pre-IND filing matters; (ii) end of Phase II matters; or (iii) pre-NDA filing matters.&#160; [***].</font></div>
          </td>
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    <div>&#160;</div>
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          </td>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">5.4.3</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>[</u></font><font style="font-size: 10pt;"><u>***</u><font style="font-weight: bold;"><u>] Regulatory Meetings</u></font>.&#160; JBI will [***] of any meetings JBI
                has or plans to have with a Regulatory Authority regarding pre-approval or Approval matters for a Product or that directly relate to ***], and may allow [***].&#160; In addition, JBI will provide Isis with as much advance written notice as
                practicable of any [***] Regulatory Authorities, and JBI [***].</font></div>
          </td>
        </tr>

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    <div>&#160;</div>
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          </td>
          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">5.4.4</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Regulatory Communications</u></font><font style="font-size: 10pt;">.&#160; [***], JBI [***] provide Isis with copies of documents and communications submitted to, or
                received from, Regulatory Authorities [***] that materially impact the Development or Commercialization of Products for [***], and JBI will [***] such documents and communications.</font></div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" id="DSPFPageBreakArea">
      <div style="text-align: center;" id="DSPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;" id="DSPFPageNumber">18</font></div>
      <div style="page-break-after: always;" id="DSPFPageBreak">
        <hr style="border-width: 0px; clear: both; margin: 4px 0px; width: 100%; height: 2px; color: #000000; background-color: #000000;" noshade="noshade"></div>
      <div style="width: 100%;" id="DSPFPageHeader">Confidential</div>
    </div>
    <table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">5.4.5</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Class Generic Claims</u></font><font style="font-size: 10pt;">.&#160; To the extent JBI intends to make any claims in a Product label or regulatory filing that are
                class generic to ASOs, JBI will provide such claims and regulatory filings to Isis in advance and will consider in good faith any proposals and comments made by Isis.</font></div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">5.4.6</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>End of Obligations if [</u></font><font style="font-size: 10pt;">***<font style="font-weight: bold;"><u>]</u></font>.&#160; JBI&#8217;s obligations under Section 5.4.2,
                Section 5.4.3,&#160; and Section 5.4.4 will cease with respect to a particular Product if [***].</font></div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" 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 style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Applicable Laws</u></font><font style="font-size: 10pt;">.&#160; JBI will use commercially reasonable efforts perform its activities pursuant to this Agreement in
                compliance with GLP, GCP and GMP, in each case as applicable under the laws and regulations of the country and the state and local government wherein such activities are conducted.</font></div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">5.6</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Isis&#8217; Antisense Safety Database</u></font><font style="font-size: 10pt;">.</font></div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 63pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">(a)</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>JBI will provide Isis with copies of [***] and the [***] within [***] days following the date such information is [***], as applicable.&#160; JBI will [***].&#160; All such information disclosed by JBI to Isis will be JBI Confidential Information.&#160;
              JBI will deliver all such information to Isis Pharmaceuticals, Inc., 2855 Gazelle Court, Carlsbad, California 92010, Attention: Chief Medical Officer (or to such other address/contact designated in writing by Isis).&#160; JBI will also cause its
              Affiliates and Sublicensees to comply with this <u>Section 5.6(a)</u>.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 63pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">(b)</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>During the term of this Agreement, if requested by JBI, JBI and Isis will [***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <div style="text-align: center; font-weight: bold;">ARTICLE 6. FINANCIAL PROVISIONS</div>
    <div>&#160;</div>
    <table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">6.1</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Option Fee</u></font><font style="font-size: 10pt;">.&#160; In partial consideration for JBI&#8217;s Options hereunder, within five Business Days following the Effective
                Date, JBI will pay Isis an Option fee equal to $10,000,000 for each of the three Drug Discovery Programs for an aggregate payment of $30,000,000.</font></div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">6.2</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Fourth Target Fee</u></font><font style="font-size: 10pt;">.&#160; If JBI elects to designate a fourth target, JBI will pay Isis $[***] within [***] days of JBI&#8217;s
                written notice to Isis designating such target.</font></div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <div>
      <table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">

          <tr>
            <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">6.3</font></td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Milestone Payments for Achievement of Pre-Licensing Milestone Event</u></font><font style="font-size: 10pt;">.&#160; As further consideration for JBI&#8217;s Options and
                  Licenses hereunder, on a Collaboration Target-by-Collaboration Target basis, JBI will pay to Isis a milestone payment of $[***] for achievement of [***] for such Collaboration Target (each, a &#8220;<font style="font-weight: bold; font-style: italic;">Pre-Licensing Milestone Event</font>&#8221;).&#160; Isis shall provide JBI with written notice of achievement of [***] and JBI shall make such payment within [***] days of receipt of such notification.&#160; With respect to [***], the Parties
                  agree that [***] is deemed to have been achieved so that Isis may [***], and JBI will make the associated payment under this <u>Section 6.3</u> within [***] days of the Effective Date; <u>provided</u> such payment does not limit the
                  Parties&#8217; obligation to conduct the activities set forth in the Drug Discovery Plan for [***].</font></div>
            </td>
          </tr>

      </table>
    </div>
    <div> <br>
    </div>
    <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" id="DSPFPageBreakArea">
      <div style="text-align: center;" id="DSPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;" id="DSPFPageNumber">19</font></div>
      <div style="page-break-after: always;" id="DSPFPageBreak">
        <hr style="border-width: 0px; clear: both; margin: 4px 0px; width: 100%; height: 2px; color: #000000; background-color: #000000;" noshade="noshade"></div>
      <div style="width: 100%;" id="DSPFPageHeader">Confidential</div>
    </div>
    <table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">6.4</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>License Fee</u></font><font style="font-size: 10pt;">.&#160; On an Option-by-Option basis, together with JBI&#8217;s written notice to Isis stating that JBI is exercising
                the Option with respect to the Drug Discovery Program for a Collaboration Target in accordance with this Agreement, JBI will pay to Isis the applicable one-time license fee set forth in <font style="font-variant: small-caps;"><u>Table 1</u></font>
                below (each, a &#8220;<font style="font-weight: bold; font-style: italic;">License Fee</font>&#8221;):</font></div>
          </td>
        </tr>

    </table>
    <div style="text-align: justify;">&#160;<br>
      <table id="z45f4b04968844bf1ab7325df0455c15a" 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 rowspan="1" style="vertical-align: middle; background-color: rgb(191, 191, 191); border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);" colspan="3">
              <div style="text-align: center; font-variant: small-caps; font-weight: bold;"><u>Table 1</u></div>
            </td>
          </tr>
          <tr>
            <td colspan="1" style="width: 1%; vertical-align: middle; background-color: rgb(217, 217, 217); border-left: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">&#160;</td>
            <td style="width: 49%; vertical-align: middle; background-color: rgb(217, 217, 217); border-right: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
              <div style="font-weight: bold;">Option</div>
            </td>
            <td style="width: 50%; vertical-align: middle; background-color: rgb(217, 217, 217); border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
              <div style="text-align: center; font-weight: bold;">License Fee</div>
            </td>
          </tr>
          <tr>
            <td colspan="1" style="width: 1%; vertical-align: middle; border-left: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">&#160;</td>
            <td style="width: 49%; vertical-align: middle; border-right: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
              <div>[***]</div>
            </td>
            <td style="width: 50%; vertical-align: middle; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
              <div style="text-align: center;">$[***]</div>
            </td>
          </tr>
          <tr>
            <td colspan="1" style="width: 1%; vertical-align: middle; border-left: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">&#160;</td>
            <td style="width: 49%; vertical-align: middle; border-right: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
              <div>[***]</div>
            </td>
            <td style="width: 50%; vertical-align: middle; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
              <div style="text-align: center;">$[***]</div>
            </td>
          </tr>

      </table>
    </div>
    <div>&#160;</div>
    <table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" 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 style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Milestone Payments for Achievement of Post-Licensing Milestone Events</u></font><font style="font-size: 10pt;">.&#160; On a Drug Discovery Program-by-Drug Discovery
                Program basis, JBI will pay to Isis the applicable milestone payment set forth in <font style="font-variant: small-caps;"><u>Table 2</u></font> below for the first achievement of the corresponding milestone event in <font style="font-variant: small-caps;"><u>Table 2</u></font> (each, a <font style="font-style: italic;">&#8220;</font><font style="font-weight: bold; font-style: italic;">Post-Licensing</font><font style="font-style: italic;">&#160;</font><font style="font-weight: bold; font-style: italic;">Milestone Event</font><font style="font-style: italic;">&#8221;</font>) by the first Product against such Collaboration Target to achieve such Post-Licensing Milestone Event:</font></div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <div>
      <table id="zdca9b7ec28b0400b9e0ed300d6c397a3" 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 rowspan="1" style="vertical-align: middle; background-color: rgb(191, 191, 191); border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);" colspan="3">
              <div style="text-align: center; font-variant: small-caps; font-weight: bold;"><u>Table 2</u></div>
            </td>
          </tr>
          <tr>
            <td colspan="1" style="width: 1%; vertical-align: middle; background-color: rgb(217, 217, 217); border-left: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">&#160;</td>
            <td style="width: 49%; vertical-align: middle; background-color: rgb(217, 217, 217); border-right: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
              <div style="font-weight: bold;">Post-Licensing Milestone Event</div>
            </td>
            <td style="width: 50%; vertical-align: middle; background-color: #D9D9D9; border-left: #000000 2px solid; border-right: #000000 2px solid; border-top: #000000 2px solid; border-bottom: #000000 2px solid;">
              <div style="text-align: center; font-weight: bold;">Milestone Event Payment</div>
            </td>
          </tr>
          <tr>
            <td colspan="1" style="width: 1%; vertical-align: middle; border-left: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">&#160;</td>
            <td style="width: 49%; vertical-align: middle; border-right: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
              <div>[***]</div>
            </td>
            <td style="width: 50%; vertical-align: middle; border-left: #000000 2px solid; border-right: #000000 2px solid; border-top: #000000 2px solid; border-bottom: #000000 2px solid;">
              <div style="text-align: center;">$[***]</div>
            </td>
          </tr>
          <tr>
            <td colspan="1" style="width: 1%; vertical-align: middle; border-left: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">&#160;</td>
            <td style="width: 49%; vertical-align: middle; border-right: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
              <div>[***]</div>
            </td>
            <td style="width: 50%; vertical-align: middle; border-left: #000000 2px solid; border-right: #000000 2px solid; border-top: #000000 2px solid; border-bottom: #000000 2px solid;">
              <div style="text-align: center;">$[***]</div>
            </td>
          </tr>
          <tr>
            <td colspan="1" style="width: 1%; vertical-align: middle; border-left: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">&#160;</td>
            <td style="width: 49%; vertical-align: middle; border-right: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
              <div>[***]*</div>
            </td>
            <td style="width: 50%; vertical-align: middle; border-left: #000000 2px solid; border-right: #000000 2px solid; border-top: #000000 2px solid; border-bottom: #000000 2px solid;">
              <div style="text-align: center;">$[***]*</div>
            </td>
          </tr>
          <tr>
            <td colspan="1" style="width: 1%; vertical-align: middle; border-left: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">&#160;</td>
            <td style="width: 49%; vertical-align: middle; border-right: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
              <div>[***]</div>
            </td>
            <td style="width: 50%; vertical-align: middle; border-left: #000000 2px solid; border-right: #000000 2px solid; border-top: #000000 2px solid; border-bottom: #000000 2px solid;">
              <div style="text-align: center;">$[***]</div>
            </td>
          </tr>
          <tr>
            <td colspan="1" style="width: 1%; vertical-align: middle; border-left: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">&#160;</td>
            <td style="width: 49%; vertical-align: middle; border-right: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
              <div>[***]</div>
            </td>
            <td style="width: 50%; vertical-align: middle; border-left: #000000 2px solid; border-right: #000000 2px solid; border-top: #000000 2px solid; border-bottom: #000000 2px solid;">
              <div style="text-align: center;">$[***]</div>
            </td>
          </tr>
          <tr>
            <td colspan="1" style="width: 1%; vertical-align: middle; border-left: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">&#160;</td>
            <td style="width: 49%; vertical-align: middle; border-right: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
              <div>[***]</div>
            </td>
            <td style="width: 50%; vertical-align: middle; border-left: #000000 2px solid; border-right: #000000 2px solid; border-top: #000000 2px solid; border-bottom: #000000 2px solid;">
              <div style="text-align: center;">$[***]</div>
            </td>
          </tr>
          <tr>
            <td colspan="1" style="width: 1%; vertical-align: middle; border-left: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">&#160;</td>
            <td style="width: 49%; vertical-align: middle; border-right: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
              <div>[***]</div>
            </td>
            <td style="width: 50%; vertical-align: middle; border-left: #000000 2px solid; border-right: #000000 2px solid; border-top: #000000 2px solid; border-bottom: #000000 2px solid;">
              <div style="text-align: center;">$[***]</div>
            </td>
          </tr>
          <tr>
            <td colspan="1" style="width: 1%; vertical-align: middle; border-left: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">&#160;</td>
            <td style="width: 49%; vertical-align: middle; border-right: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
              <div>[***]</div>
            </td>
            <td style="width: 50%; vertical-align: middle; border-left: #000000 2px solid; border-right: #000000 2px solid; border-top: #000000 2px solid; border-bottom: #000000 2px solid;">
              <div style="text-align: center;">$[***]</div>
            </td>
          </tr>
          <tr>
            <td colspan="1" style="width: 1%; vertical-align: middle; border-left: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">&#160;</td>
            <td style="width: 49%; vertical-align: middle; border-right: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
              <div>[***]</div>
            </td>
            <td style="width: 50%; vertical-align: middle; border-left: #000000 2px solid; border-right: #000000 2px solid; border-top: #000000 2px solid; border-bottom: #000000 2px solid;">
              <div style="text-align: center;">$[***]</div>
            </td>
          </tr>
          <tr>
            <td colspan="1" style="width: 1%; vertical-align: middle; border-left: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">&#160;</td>
            <td style="width: 49%; vertical-align: middle; border-right: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
              <div>[***]</div>
            </td>
            <td style="width: 50%; vertical-align: middle; border-left: #000000 2px solid; border-right: #000000 2px solid; border-top: #000000 2px solid; border-bottom: #000000 2px solid;">
              <div style="text-align: center;">$[***]</div>
            </td>
          </tr>
          <tr>
            <td colspan="1" style="width: 1%; vertical-align: middle; border-left: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">&#160;</td>
            <td style="width: 49%; vertical-align: middle; border-right: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
              <div>[***]</div>
            </td>
            <td style="width: 50%; vertical-align: middle; border-left: #000000 2px solid; border-right: #000000 2px solid; border-top: #000000 2px solid; border-bottom: #000000 2px solid;">
              <div style="text-align: center;">$[***]</div>
            </td>
          </tr>
          <tr>
            <td colspan="1" style="width: 1%; vertical-align: middle; border-left: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">&#160;</td>
            <td style="width: 49%; vertical-align: middle; border-right: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
              <div>[***]</div>
            </td>
            <td style="width: 50%; vertical-align: middle; border-left: #000000 2px solid; border-right: #000000 2px solid; border-top: #000000 2px solid; border-bottom: #000000 2px solid;">
              <div style="text-align: center;">$[***]</div>
            </td>
          </tr>

      </table>
    </div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">*[***].</div>
    <div><br>
    </div>
    <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" id="DSPFPageBreakArea">
      <div style="text-align: center;" id="DSPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;" id="DSPFPageNumber">20</font></div>
      <div style="page-break-after: always;" id="DSPFPageBreak">
        <hr style="border-width: 0px; clear: both; margin: 4px 0px; width: 100%; height: 2px; color: #000000; background-color: #000000;" noshade="noshade"></div>
      <div style="width: 100%;" id="DSPFPageHeader">Confidential</div>
    </div>
    <table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" 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 style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Limitations on Milestone Payments; Exceptions; Notice</u></font><font style="font-size: 10pt;">.</font></div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">6.6.1</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>Each milestone payment set forth in <font style="font-variant: small-caps;"><u>Table 2</u></font> above will be paid only once per Drug Discovery Program upon the first achievement of the applicable Post-Licensing Milestone Event,
              regardless of how many Products under a Drug Discovery Program achieve such Milestone Event.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">6.6.2</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>If a particular Post-Licensing Milestone Event is not achieved because Development activities transpired such that achievement of such earlier Milestone Event was unnecessary or did not otherwise occur, then upon achievement of the next
              Post-Licensing Milestone Event to be achieved, the Post-Licensing Milestone Event payment applicable to such earlier Post-Licensing Milestone Event will also be due.&#160; For example, if a Party proceeds directly to [***] without achieving the
              [***] then upon achieving the [***] Milestone Event, both the [***] and [***] Milestone Event payments are due.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">6.6.3</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>Each time a Post-Licensing Milestone Event is achieved under this <u>ARTICLE 6</u>, JBI will send Isis, or Isis will send JBI, as the case may be, a written notice thereof promptly (but no later than [***]) following the date of
              achievement of such Milestone Event, and such payment will be due within [***] of the date such notice was delivered.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">6.7</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Net Sales Milestone Payments</u></font><font style="font-size: 10pt;">.&#160; On a Drug Discovery Program-by-Drug Discovery Program basis, for the first Calendar Year
                in which Annual worldwide Net Sales of the first Product progressed from a Drug Discovery Program that achieves or exceeds each of the levels of Annual worldwide Net Sales set forth in <font style="font-variant: small-caps;">Table 3</font>
                below (each, a &#8220;<font style="font-weight: bold; font-style: italic;">Sales Milestone Event</font>&#8221;), JBI will pay Isis the corresponding one-time Sales Milestone Event payment within [***] days of the end of the Calendar Quarter during such
                Calendar Year in which such Sales Milestone Event occurs.</font></div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <div>
      <table id="z4501531f06f949c18c83d0ed056b262e" 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 rowspan="1" style="vertical-align: middle; background-color: rgb(191, 191, 191); border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);" colspan="3">
              <div style="text-align: center; font-variant: small-caps; font-weight: bold;"><u>Table 3</u></div>
            </td>
          </tr>
          <tr>
            <td colspan="1" style="width: 1%; vertical-align: middle; background-color: rgb(217, 217, 217); border-left: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">&#160;</td>
            <td style="width: 49%; vertical-align: middle; background-color: rgb(217, 217, 217); border-right: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
              <div style="font-weight: bold;">Annual Worldwide Net Sales</div>
            </td>
            <td style="width: 49.97%; vertical-align: middle; background-color: #D9D9D9; border-left: #000000 2px solid; border-right: #000000 2px solid; border-top: #000000 2px solid; border-bottom: #000000 2px solid;">
              <div style="text-align: center; font-weight: bold;">Sales Milestone Event Payment</div>
            </td>
          </tr>
          <tr>
            <td colspan="1" style="width: 1%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">&#160;</td>
            <td style="width: 49%; vertical-align: top; border-right: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
              <div style="text-align: center;">&#8805; $[***]</div>
            </td>
            <td style="width: 49.97%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-top: #000000 2px solid; border-bottom: #000000 2px solid;">
              <div style="text-align: center;">$[***]</div>
            </td>
          </tr>
          <tr>
            <td colspan="1" style="width: 1%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">&#160;</td>
            <td style="width: 49%; vertical-align: top; border-right: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
              <div style="text-align: center;">&#8805; $[***]</div>
            </td>
            <td style="width: 49.97%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-top: #000000 2px solid; border-bottom: #000000 2px solid;">
              <div style="text-align: center;">$[***]</div>
            </td>
          </tr>
          <tr>
            <td colspan="1" style="width: 1%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">&#160;</td>
            <td style="width: 49%; vertical-align: top; border-right: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
              <div style="text-align: center;">&#8805; $[***]</div>
            </td>
            <td style="width: 49.97%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-top: #000000 2px solid; border-bottom: #000000 2px solid;">
              <div style="text-align: center;">$[***]</div>
            </td>
          </tr>

      </table>
    </div>
    <div><br>
    </div>
    <div style="text-align: justify; margin-left: 36pt;">Each Sales Milestone Event payment set forth in <font style="font-variant: small-caps;">Table 3</font> above will be due only one time per Drug Discovery Program, for the first Calendar Year in
      which the corresponding Sales Milestone Event occurs.&#160; If more than one of the above Sales Milestone Events is achieved in the same year, JBI will pay all applicable milestone payments.</div>
    <div>&#160;</div>
    <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" id="DSPFPageBreakArea">
      <div style="text-align: center;" id="DSPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;" id="DSPFPageNumber">21</font></div>
      <div style="page-break-after: always;" id="DSPFPageBreak">
        <hr style="border-width: 0px; clear: both; margin: 4px 0px; width: 100%; height: 2px; color: #000000; background-color: #000000;" noshade="noshade"></div>
      <div style="width: 100%;" id="DSPFPageHeader">Confidential</div>
    </div>
    <table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">6.8</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Royalty Payments to Isis</u></font><font style="font-size: 10pt;">.</font></div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">6.8.1</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>JBI Royalty</u></font><font style="font-size: 10pt;">.&#160; As partial consideration for the rights granted to JBI hereunder, subject to the provisions of this <u>Section


                  6.8.1</u> and <u>Section 6.8.2</u>, JBI will pay to Isis royalties on a Product-by-Product basis, on Annual worldwide Net Sales of Products included in the applicable Drug Discovery Program sold by JBI, its Affiliates or Sublicensees, on
                a country-by-country basis, in each case in the amounts as follows in <font style="font-variant: small-caps;"><u>Table 4</u></font> below (the &#8220;<font style="font-weight: bold; font-style: italic;">JBI Royalty</font>&#8221;):</font></div>
          </td>
        </tr>

    </table>
    <br>
    <div>
      <div>
        <table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: #000000;" id="z9c6561d77c404ee9ace1c4b76b8949e4" cellpadding="0" cellspacing="0">

            <tr>
              <td style="width: 100%; vertical-align: top; background-color: rgb(191, 191, 191); border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0);">
                <div style="text-align: center; font-variant: small-caps; font-weight: bold;"><u>Table 4</u></div>
              </td>
            </tr>

        </table>
      </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: 15.41%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
            <div style="text-align: center; font-weight: bold;">Royalty</div>
            <div style="text-align: center; font-weight: bold;">Tier</div>
          </td>
          <td colspan="1" style="width: 1%; vertical-align: bottom; border-left: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">&#160;</td>
          <td style="width: 68%; vertical-align: bottom; border-right: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
            <div style="font-weight: bold;">Annual Worldwide Net Sales of Products</div>
          </td>
          <td style="width: 16%; vertical-align: middle; border-left: #000000 2px solid; border-right: #000000 2px solid; border-top: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center; font-weight: bold;">Royalty</div>
            <div style="text-align: center; font-weight: bold;">Rate</div>
          </td>
        </tr>
        <tr>
          <td style="width: 15.41%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0);">
            <div style="text-align: center;">1</div>
          </td>
          <td colspan="1" style="width: 1%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0);">&#160;</td>
          <td style="width: 68%; vertical-align: top; border-right: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0);">
            <div>For the portion of Annual Worldwide Net Sales</div>
            <div>&lt; $[***]</div>
          </td>
          <td style="width: 16%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0);">
            <div style="text-align: center;">[***]%</div>
          </td>
        </tr>
        <tr>
          <td style="width: 15.41%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);" rowspan="1">&#160;</td>
          <td colspan="1" style="width: 1%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);" rowspan="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);" rowspan="1">&#160;</td>
          <td style="width: 16%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);" rowspan="1">&#160;</td>
        </tr>
        <tr>
          <td style="width: 15.41%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0);">
            <div style="text-align: center;">2</div>
          </td>
          <td colspan="1" style="width: 1%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0);">&#160;</td>
          <td style="width: 68%; vertical-align: top; border-right: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0);">
            <div>For the portion of Annual Worldwide Net Sales</div>
            <div><u>&gt;</u> $[***] but &lt; $[***]</div>
          </td>
          <td style="width: 16%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0);">
            <div style="text-align: center;">[***]%</div>
          </td>
        </tr>
        <tr>
          <td style="width: 15.41%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);" rowspan="1">&#160;</td>
          <td colspan="1" style="width: 1%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0);" rowspan="1">&#160;</td>
          <td style="width: 68%; vertical-align: top; border-right: 2px solid rgb(0, 0, 0);" rowspan="1">&#160;</td>
          <td style="width: 16%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);" rowspan="1">&#160;</td>
        </tr>
        <tr>
          <td style="width: 15.41%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0);">
            <div style="text-align: center;">3</div>
          </td>
          <td colspan="1" style="width: 1%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0);">&#160;</td>
          <td style="width: 68%; vertical-align: top; border-right: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0);">
            <div>For the portion of Annual Worldwide Net Sales</div>
            <div><u>&gt;</u> $[***]</div>
          </td>
          <td style="width: 16%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0);">
            <div style="text-align: center;">[***]%</div>
          </td>
        </tr>
        <tr>
          <td style="width: 15.41%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);" rowspan="1">&#160;</td>
          <td colspan="1" style="width: 1%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);" rowspan="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);" rowspan="1">&#160;</td>
          <td style="width: 16%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);" rowspan="1">&#160;</td>
        </tr>

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

        <tr>
          <td style="width: 63pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">(a)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>Annual worldwide Net Sales will be calculated by [***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 63pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">(b)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>For purposes of clarification, any Isis Product-Specific Patents and Jointly-Owned Program Patents assigned to JBI as set forth in <u>Section 4.2.1</u> will still be royalty-bearing and considered Isis Product-Specific Patents and
              Jointly-Owned Program Patents, respectively, for determining the royalty term and applicable royalty rates under this <u>ARTICLE 6</u>.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">6.8.2</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Application of Royalty Rates</u></font><font style="font-size: 10pt;">.&#160; All royalties set forth under <u>Section 6.8.1</u> are subject to the provisions of
                this <u>Section 6.8.2</u>, and are payable as follows:</font></div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 63pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">(a)</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Royalty Period</u></font><font style="font-size: 10pt;">.&#160; JBI&#8217;s obligation to pay Isis the JBI Royalty above with respect to Products will continue on a
                country-by-country and Product-by-Product basis from the date of First Commercial Sale of such Product in a country until the later of the date of expiration of (i) the last Valid Claim within the Licensed Patents or Program Patents
                Covering such Product in the country in which such Product is made, used or sold, [***] (such royalty period, the &#8220;<font style="font-weight: bold; font-style: italic;">Royalty Period</font>&#8221;).</font></div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 63pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">(b)</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Royalty Reduction</u></font><font style="font-size: 10pt;"><u> &#8211; </u><font style="font-weight: bold;"><u>U.S. Loss of Patent Rights.</u></font>&#160; If (i) there is
                no longer a Valid Claim within the Licensed Patents or Program Patents Covering a Product in the U.S., and [***], then JBI may reduce the royalty payments for sales in the U.S. described in Table 4 by [***] ([***]) percent.&#160; JBI shall make
                the reduced royalty payments to Isis for the remainder of the Royalty Period.</font></div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" id="DSPFPageBreakArea">
      <div style="text-align: center;" id="DSPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;" id="DSPFPageNumber">22</font></div>
      <div style="page-break-after: always;" id="DSPFPageBreak">
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      <div style="width: 100%;" id="DSPFPageHeader">Confidential</div>
    </div>
    <table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 63pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">(c)</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Royalty Reduction </u></font><font style="font-size: 10pt;"><u>&#8211; </u><font style="font-weight: bold;"><u>Early Generic Product Entry.</u></font>&#160; If after the
                [***] anniversary of the First Commercial Sale of a Product, in a given country within the Territory, entry of a Generic Product has occurred prior to the expiry of the last Licensed Patent or Program Patent with a Valid Claim covering a
                Product, and either (i) subsequently the sales of the Product have declined by [***] percent ([***]%) or more but less than [***] percent ([***]%) as compared to the [***] Calendar Quarters [***] prior to such Generic Product entry, then
                JBI may reduce the royalty payments for sales in such country described in Table 4 by [***] percent ([***]%), or (ii) subsequently the sales of the Product have declined by [***] percent ([***]%) or more as compared to the [***] Calendar
                Quarters [***] prior to such Generic Product entry, then no further royalty payments shall be due to Isis for such Product in such country;<u> provided</u>, if JBI reduced or ceased paying the royalty payments under this Section, and
                thereafter a court of competent jurisdiction determines that the Licensed Patent is valid and infringed by the Generic Product, JBI shall resume making royalty payments at the full amount as of the date of such court order.</font></div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 63pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">(d)</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Limitation on Aggregate Reduction for JBI Royalties</u></font><font style="font-size: 10pt;">.</font></div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 108pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">(i)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>In no event will the aggregate royalty offsets under <u>Section 6.9.3(b)</u> reduce the royalties payable to Isis on Net Sales of a Product in any given period to [***]% of the JBI Royalty rates listed in <font style="font-variant: small-caps;"><u>Table 4</u></font>.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 108pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">(ii)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>In addition, in no event will the aggregate royalty offsets and reductions under Section&#160; <u>6.8.2(c)</u> (as applicable) and<u> Section 6.9.3(b)</u> reduce the royalties payable to Isis on Net Sales of a Product in any given period to
              less than [***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 63pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">(e)</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>End of Royalty Obligation</u></font><font style="font-size: 10pt;">.&#160; On a country-by-country and Product-by-Product basis JBI&#8217;s obligation to make royalty
                payments hereunder for such Product in such country will end on the expiration of the Royalty Period at which time JBI will have a fully paid up license under the Licensed Patents; <u>provided</u> [***].</font></div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">6.9</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Third Party Payment Obligations</u></font><font style="font-size: 10pt;">.</font></div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">6.9.1</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Existing Isis In-License Agreements</u></font><font style="font-size: 10pt;">.</font></div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 63pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">(a)</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>Certain of the Licensed Technology Controlled by Isis as of the Effective Date licensed to JBI under <u>Section 4.1.1</u> was in-licensed or was acquired by Isis under the agreements with Third Party licensors or sellers listed on <font style="font-variant: small-caps;"><u>Schedule </u></font><u>6.9.1</u> (all such license or purchase agreements being the &#8220;<font style="font-weight: bold; font-style: italic;">Isis In-License Agreements</font>&#8221;).&#160; Certain license fees,
              maintenance fees, milestone payments, royalties or similar payments that apply to Products may become payable by Isis to such Third Parties under the Isis In-License Agreements based on the Development and Commercialization of a Product by
              JBI under this Agreement.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" id="DSPFPageBreakArea">
      <div style="text-align: center;" id="DSPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;" id="DSPFPageNumber">23</font></div>
      <div style="page-break-after: always;" id="DSPFPageBreak">
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      <div style="width: 100%;" id="DSPFPageHeader">Confidential</div>
    </div>
    <table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 63pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">(b)</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>Any payment obligations arising under the Isis In-License Agreements as existing on the Effective Date and up until JBI exercises an Option under this Agreement, as they apply to the Isis Core Technology used by Products developed under
              this Agreement will be paid by [***], and [***], as [***].&#160; In the event JBI determines that it wishes to obtain a sublicense under the Isis In-License Agreements, [***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">6.9.2</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>New In-Licensed Isis Product-Specific Patents</u></font><font style="font-size: 10pt;">.&#160; If after the Effective Date, Isis obtains Third Party Patent Rights
                necessary or useful to Develop, Manufacture or Commercialize a Product that would have been considered an Isis Product-Specific Patent had Isis Controlled such Patent Rights on the Effective Date, to the extent Controlled by Isis, Isis will
                include such Third Party Patent Rights in the license granted to JBI under <u>Section 4.1.1</u> if JBI agrees in writing to pay Isis (i) [***] and (ii) [***].&#160; In the event JBI declines to pay Isis [***], nothing in this Agreement [***].</font></div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">6.9.3</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Additional Core IP In-License Agreements</u></font><font style="font-size: 10pt;">.</font></div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 63pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">(a)</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>JBI will promptly provide Isis written notice of any Additional Core IP JBI believes it has identified and Isis will have the first right, but not the obligation, to negotiate with, and obtain a license from the Third Party Controlling
              such Additional Core IP.&#160; If Isis obtains such a Third Party license, Isis will include such Additional Core IP in the license granted to JBI under <u>Section 4.1.1</u>, and any financial obligations under such Third Party agreement will be
              [***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 63pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">(b)</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>If, however, Isis elects not to obtain such a license to such Third Party intellectual property, Isis will so notify JBI, and JBI may obtain such a Third Party license and, subject to <u>Section 6.8.2(d)</u>, JBI may offset an amount
              equal to [***]% of any [***] paid by JBI under such Third Party license against any [***] of this Agreement in such country for [***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 63pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">(c)</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>If it is unclear whether certain intellectual property identified by JBI pursuant to <u>Section 6.9.3(a)</u> is Additional Core IP under <u>Section 6.9.3(b)</u>, Isis will send written notice to such effect to JBI, and the Parties will
              engage a mutually agreed upon independent Third Party intellectual property lawyer with expertise in the patenting of ASOs, and appropriate professional credentials in the relevant jurisdiction, to determine the question of whether or not
              such Third Party intellectual property is Additional Core IP.&#160; The determination of the Third Party expert engaged under the preceding sentence will be binding on the Parties solely for purposes of determining whether JBI is permitted to
              [***].&#160; The costs of any Third Party expert engaged under this <u>Section 6.9.3(c)</u> will be paid by the Party against whose position the Third Party lawyer&#8217;s determination is made.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" id="DSPFPageBreakArea">
      <div style="text-align: center;" id="DSPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;" id="DSPFPageNumber">24</font></div>
      <div style="page-break-after: always;" id="DSPFPageBreak">
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      <div style="width: 100%;" id="DSPFPageHeader">Confidential</div>
    </div>
    <table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">6.9.4</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Other Third Party Payments</u></font><font style="font-size: 10pt;">.</font></div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 63pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">(a)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Isis&#8217; Third Party Agreements</u></font><font style="font-size: 10pt;">.&#160; Except as otherwise expressly agreed to by JBI under <u>Section 6.9.2</u>, after Option
                exercise, JBI will be responsible for paying [***]% of the [***] arising under any Third Party agreements entered into by Isis.</font></div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 63pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">(b)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>JBI&#8217;s Third Party Agreements</u></font><font style="font-size: 10pt;">.&#160; Without limiting any applicable [***] under Section 6.9.3(b), JBI will be responsible
                for paying [***]% of the [***] arising under any Third Party agreements entered into by JBI as they apply to Products.</font></div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">6.10</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Invoices.</u></font><font style="font-size: 10pt;"> Unless otherwise specified hereunder, JBI shall make payments required hereunder to Isis within [***] ([***])
                days from the date an invoice is received by JBI provided that any invoiced costs are for fees or services that have been rendered by Isis plus Out of Pocket Expenses incurred by Isis and further subject to the invoice having been received
                by JBI. All invoices must reference a valid Purchase Order (PO) Number which JBI shall provide to Isis within [***] ([***]) days of any such contracted service after the Effective Date. Isis&#8217; invoices will include Isis&#8217; good faith estimate
                of the FTE cost incurred by Isis in performing the services and the amount of Out-of Pocket Expenses incurred and charged by Isis. Before Isis commences work, JBI and Isis will agree to a budget for the work JBI requests Isis to perform
                that will include Isis&#8217; good faith estimate of the FTE cost plus Out of Pocket Expenses. Isis shall provide reasonable support for each invoice. Reasonable support means [***]. Invoices shall be sent to: Johnson &amp; Johnson Shared
                Services, P.O. Box 16540, New Brunswick, NJ 08906-6540, United States, with a copy to Immunology TA Controller, c/o J&amp;J PRD, PO Box 766, Welsh &amp; McKean Road, Spring House 19477, or via www.ap.jnj.com if Isis is established with a
                web invoice account.&#160; JBI reserves the right to return to Isis unprocessed and unpaid those invoices that do not reference a valid P.O. number.</font></div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">6.11</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Payments</u></font><font style="font-size: 10pt;">.</font></div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">6.11.1</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Commencement</u></font><font style="font-size: 10pt;">.&#160; Beginning with the Calendar Quarter in which the First Commercial Sale for a Product is made and for
                each Calendar Quarter thereafter, JBI will make royalty payments to Isis under this Agreement within [***] days following the end of each such Calendar Quarter.&#160; Each royalty payment will be accompanied by a report showing on a Product-by
                Product and country-by-country basis the gross sales, the Net Sales, and a calculation of the amount of royalty due on such Net Sales. This report shall also include the exchange rates and other methodology used in converting Net Sales into
                <u>US dollars </u>from the currencies in which sales were made in order to determine the appropriate royalty tier and royalty.&#160; If no royalties are payable in respect of a given Calendar Quarter, JBI will submit a written royalty report to
                Isis so indicating together with an explanation as to why no such royalties are payable.&#160; In addition, on a Product-by-Product basis, beginning with the Calendar Quarter in which the First Commercial Sale for such Product is made and for
                each Calendar Quarter thereafter for the next [***] ([***]) years, JBI will (based on information JBI collects, and in a format JBI uses for its own internal planning and reporting purposes) provide Isis a preliminary non-binding report
                estimating the total Net Sales of, and royalties payable to Isis for Products projected for such Calendar Quarter.&#160; JBI will endeavor to provide such preliminary non-binding report within [***] Business Days following the end of each such
                Calendar Quarter; <u>provided</u> JBI will provide such preliminary non-binding report no later than [***] Business Days following the end of each such Calendar Quarter.</font></div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" id="DSPFPageBreakArea">
      <div style="text-align: center;" id="DSPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;" id="DSPFPageNumber">25</font></div>
      <div style="page-break-after: always;" id="DSPFPageBreak">
        <hr style="border-width: 0px; clear: both; margin: 4px 0px; width: 100%; height: 2px; color: #000000; background-color: #000000;" noshade="noshade"></div>
      <div style="width: 100%;" id="DSPFPageHeader">Confidential</div>
    </div>
    <table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">6.11.2</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Mode of Payment</u></font><font style="font-size: 10pt;">.&#160; All payments under this Agreement will be (i) payable in full in U.S. dollars, regardless of the
                country(ies) in which sales are made, (ii) made by wire transfer of immediately available funds to an account designated by Isis in writing, and (iii) non-creditable, irrevocable and non-refundable.&#160; With respect to sales of Product
                invoiced in a currency other than USD, such amounts and the amounts payable hereunder shall be expressed in their USD equivalent calculated as follows: For the upcoming Calendar Year, JBI shall provide: 1) a Currency Hedge Rate(s) to be
                used for the local currency of each country of the Territory and 2) the details of such Currency Hedge Rate(s) in writing to Isis not later than [***] business days after the Currency Hedge Rate(s) are available from the GTSC or its
                Affiliates, which is customarily at the end of October.&#160; Such Currency Hedge Rate(s) will remain constant throughout the upcoming calendar year.&#160; JBI shall use the Currency Hedge Rate(s) to convert Net Sales to USD for the purpose of
                calculating royalties and Sales Milestones.</font></div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">6.11.3</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Records Retention</u></font><font style="font-size: 10pt;">.&#160; Commencing with the First Commercial Sale of a Product, JBI will keep complete and accurate records
                pertaining to the sale of Products for a period of [***] Calendar Years after the year in which such sales occurred, and in sufficient detail to permit Isis to confirm the accuracy of the Net Sales or royalties paid by JBI hereunder.</font></div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">6.12</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Audits</u></font><font style="font-size: 10pt;">.&#160; After Option exercise, during the Agreement Term and for a period of [***] Calendar Years thereafter, at the
                written request and expense of Isis, JBI will permit an independent certified public accountant of nationally recognized standing appointed by Isis and reasonably acceptable to JBI, at reasonable times and upon reasonable notice, but in no
                case more than [***], to examine such records at the location where such records are maintained as may be necessary for the sole purpose of verifying the calculation and reporting of milestones and Net Sales, and the correctness of any
                milestone and royalty payments made under this Agreement for any period within the preceding [***] Calendar Years.&#160; As a condition to examining any records of JBI, such auditor will sign a nondisclosure agreement reasonably acceptable to
                JBI in form and substance.&#160; Any and all records of JBI examined by such independent certified public accountant will be deemed JBI&#8217;s Confidential Information.&#160; The report of the independent public accountant shall be shared with JBI prior
                to distribution to Isis such that JBI can provide the independent public accountant with justifying remarks for inclusion in the report prior to sharing the conclusions of such independent public audit with Isis.&#160; Upon completion of the
                audit, the accounting firm will provide both JBI and Isis with a written report disclosing whether the royalty payments made by JBI are correct or incorrect, whether any milestone payment that became due during the audited period was timely
                reported and paid, and the specific details concerning any discrepancies (&#8220;<font style="font-weight: bold; font-style: italic;">Audit Report</font>&#8221;).&#160; If, as a result of any inspection of the books and records of JBI, it is shown that
                JBI&#8217;s royalty payments under this Agreement were less than the royalty amount which should have been paid, and/or that any milestone payment was not paid when due or at all, then JBI will make all payments required to be made by paying Isis
                the difference between such amounts to eliminate any discrepancy revealed by said inspection within [***] days of receiving the Audit Report, with interest calculated in accordance with <u>Section 6.14</u>.&#160; If, as a result of any
                inspection of the books and records of JBI, it is shown that JBI&#8217;s payments under this Agreement were greater than the royalty amount which should have been paid, then JBI will receive a credit against future royalty payments due under <u>Section


                  6.8</u> equal to the difference between the amounts paid by JBI and the royalty amounts which should have been paid.&#160; Isis will pay for such audit, except that if JBI is found to have underpaid Isis by more than [***]% of the amount that
                should have been paid, and/or not to have paid any milestone that should have been paid, JBI will reimburse Isis&#8217; reasonable costs of the audit.</font></div>
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          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">6.13</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Taxes</u></font><font style="font-size: 10pt;">.</font></div>
          </td>
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          </td>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">6.13.1</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Taxes on Income</u></font><font style="font-size: 10pt;">.&#160; Each Party will be solely responsible for the payment of all taxes imposed on its share of income
                arising directly or indirectly from the activities of the Parties under this Agreement.</font></div>
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          </td>
          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">6.13.2</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>Isis will provide JBI with any and all tax forms in advance of the due dates that may be reasonably necessary in order for JBI to lawfully not withhold tax or to withhold tax at a reduced rate under an applicable bilateral income tax
              treaty.&#160; Following JBI&#8217;s timely receipt of such tax forms from Isis, JBI will not withhold tax or will withhold tax at a reduced rate under an applicable bilateral income tax treaty, if appropriate under the applicable laws.&#160; Each Party will
              provide the other with reasonable assistance to enable the recovery, as permitted by applicable law, of withholding taxes resulting from payments made under this Agreement, such recovery to be for the benefit of the Party who would have been
              entitled to receive the money but for the application of withholding tax under this <u>Section 6.13.2</u>.</div>
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          </td>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">6.13.3</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>JBI will make all payments to Isis under this Agreement without deduction or withholding for Taxes except to the extent that any such deduction or withholding is required by law in effect at the time of payment.</div>
          </td>
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          </td>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">6.13.4</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>Any Tax required to be withheld on amounts payable under this Agreement will be paid by JBI on behalf of Isis to the appropriate governmental authority, and JBI will furnish Isis with proof of payment of such Tax. Any such Tax required to
              be withheld will be an expense of and borne by Isis. If any such Tax is assessed against and paid by JBI, then Isis will indemnify and hold harmless JBI from and against such Tax unless the assessment and payment of such Tax is a result of
              acts or omissions by JBI.</div>
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          <td style="width: 36pt; vertical-align: top; font-weight: bold;">6.13.5</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>JBI and Isis will cooperate with one another and use reasonable efforts to lawfully avoid or reduce withholding or similar obligations in respect of royalties, milestone payments and other payments made by the paying Party to the receiving
              party under this agreement, including but not limited to all documentation required by any taxing authority or reasonably requested by either Party to secure a reduction in the rate of applicable withholding Taxes or similar obligations.&#160;
              Within five Business Days of the Effective Date of this Agreement, Isis will deliver to JBI an accurate and complete Internal Revenue Service Form W-9.</div>
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          <td style="width: 36pt; vertical-align: top; font-weight: bold;">6.13.6</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>The provisions of this <u>Section 6.13</u> Are to be read in conjunction with the provisions of <u>Section 12.4</u> below.</div>
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          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">6.14</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Interest</u></font><font style="font-size: 10pt;">.&#160; Any undisputed payments to be made hereunder that are not paid on or before the date such payments are due
                under this Agreement will bear interest at a rate per annum equal to the lesser of (i) the rate announced by Bank of America (or its successor) as its prime rate in effect on the date that such payment would have been first due plus 1% or
                (ii) the maximum rate permissible under applicable law.</font></div>
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          <td style="width: 36pt; vertical-align: top; font-weight: bold;">6.15</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Paying Agent.</u></font><font style="font-size: 10pt;">&#160; Janssen Research &amp; Development, L.L.C., an Affiliate of JBI acting as a paying agent for JBI, may
                make certain payments due under this Agreement.</font></div>
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    <div>&#160;</div>
    <div style="text-align: center; font-weight: bold;">ARTICLE 7.</div>
    <div style="text-align: center; font-weight: bold;">INTELLECTUAL PROPERTY</div>
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          <td style="width: 36pt; vertical-align: top; font-weight: bold;">7.1</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Ownership</u></font><font style="font-size: 10pt;">.</font></div>
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          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">7.1.1</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Isis Technology and JBI Technology</u></font><font style="font-size: 10pt;">.&#160; As between the Parties, Isis will own and retain all of its rights, title and
                interest in and to the Licensed Know-How and Licensed Patents and JBI will own and retain all of its rights, title and interest in and to the JBI Know-How and JBI Patents, subject to any assignments, rights or licenses expressly granted by
                one Party to the other Party under this Agreement.</font></div>
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          </td>
          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">7.1.2</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Agreement Technology</u></font><font style="font-size: 10pt;">.&#160; As between the Parties, JBI is the sole owner of any Know-How discovered, developed, invented or
                created solely by or on behalf of JBI or its Affiliates during the Drug Discovery Term (&#8220;<font style="font-weight: bold; font-style: italic;">JBI Program Know-How</font>&#8221;) and any Patent Rights that claim or cover JBI Program Know-How (&#8220;<font style="font-weight: bold; font-style: italic;">JBI Program Patents</font>&#8221; and together with the JBI Program Know-How, the &#8220;<font style="font-weight: bold; font-style: italic;">JBI Program Technology</font>&#8221;), and will retain all of its
                rights, title and interest thereto, subject to any rights or licenses expressly granted by JBI to Isis under this Agreement.&#160; As between the Parties, Isis is the sole owner of any Know-How discovered, developed, invented or created solely
                by or on behalf of Isis or its Affiliates during the Drug Discovery Term (&#8220;<font style="font-weight: bold; font-style: italic;">Isis Program Know-How</font>&#8221;) and any Patent Rights that claim or cover such Know-How (&#8220;<font style="font-weight: bold; font-style: italic;">Isis Program Patents</font>&#8221; and together with the Isis Program Know-How, the &#8220;<font style="font-weight: bold; font-style: italic;">Isis Program Technology</font>&#8221;), and will retain all of
                its rights, title and interest thereto, subject to any assignment, rights or licenses expressly granted by Isis to JBI under this Agreement.&#160; Any Know-How discovered, developed, invented or created jointly during the Drug Discovery Term by
                or on behalf of both Parties or their respective Affiliates or Third Parties acting on their behalf (&#8220;<font style="font-weight: bold; font-style: italic;">Jointly-Owned Program Know-How</font>&#8221;), and any Patent Rights that claim or cover
                such Jointly-Owned Program Know-How (&#8220;<font style="font-weight: bold; font-style: italic;">Jointly-Owned Program Patents</font>&#8221;, and together with the Jointly-Owned Program Know-How, the &#8220;<font style="font-weight: bold; font-style: italic;">Jointly-Owned Program Technology</font>&#8221;), are owned jointly by JBI and Isis on an equal and undivided basis, including all rights, title and interest thereto, subject to any rights or licenses expressly granted by one Party to
                the other Party under this Agreement.&#160; Except as expressly provided in this Agreement, neither Party will have any obligation to account to the other for profits with respect to, or to obtain any consent of the other Party to license or
                exploit, Jointly-Owned Program Technology by reason of joint ownership thereof, and each Party hereby waives any right it may have under the laws of any jurisdiction to require any such consent or accounting.&#160; Each Party will promptly
                disclose to the other Party in writing, and will cause its Affiliates to so disclose, the discovery, development, invention or creation of any Jointly-Owned Program Technology.&#160; The JBI Program Patents, Isis Program Patents and
                Jointly-Owned Program Patents are collectively referred to herein as the &#8220;<font style="font-weight: bold; font-style: italic;">Program Patents</font>.&#8221;</font></div>
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          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">7.1.3</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Joint Patent Committee</u></font><font style="font-size: 10pt;">.</font></div>
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          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">(a)</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>The Parties will establish a &#8220;<font style="font-weight: bold; font-style: italic;">Joint Patent Committee</font>&#8221; or &#8220;<font style="font-weight: bold; font-style: italic;">JPC</font>.&#8221;&#160; The JPC will serve as the primary contact and forum
              for discussion between the Parties with respect to intellectual property matters arising under this Agreement, and will cooperate with respect to the activities set forth in this 7.1.3.&#160; Isis&#8217; obligation to participate in the JPC will
              terminate upon the end of the Drug Discovery Term.&#160; Thereafter, Isis will have the right, but not the obligation, to participate in JPC meetings.&#160; If the JPC dissolves, each Party will designate a patent attorney who will be responsible for
              intellectual property matters under this Agreement.&#160; A strategy will be discussed with regard to (i) prosecution and maintenance, defense and enforcement of Isis Product-Specific Patents that would be or are licensed to JBI under <u>Section
                4.1.1</u> in connection with a Product and JBI Product-Specific Patents, (ii) defense against allegations of infringement of Third Party Patent Rights, (iii) licenses to Third Party Patent Rights or Know-How, and (iv) the timing and subject
              matter of any potential publications regarding a Drug Discovery Program, in each case to the extent such matter would be reasonably likely to have a material impact on the Agreement or the licenses granted hereunder, which strategy will be
              considered in good faith by the Party entitled to prosecute, enforce and defend such Patent Rights, as applicable, hereunder, but will not be binding on such Party.</div>
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          <td style="width: 36pt; vertical-align: top; font-weight: bold;">(b)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>In addition, the Joint Patent Committee will be responsible for the determination of inventorship of Program Patents in accordance with United States patent laws.&#160; In case of a dispute in the Joint Patent Committee (or otherwise between
              Isis and JBI) over inventorship of Program Patents, if the Joint Patent Committee cannot resolve such dispute, even after seeking the JRC&#8217;s input, such dispute will be resolved by independent patent counsel not engaged or regularly employed
              in the past two years by either Party and reasonably acceptable to both Parties.&#160; The decision of such independent patent counsel will be binding on the Parties.&#160; Expenses of such patent counsel will be shared equally by the Parties.</div>
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          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">(c)</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>The JPC will comprise an equal number of members from each Party.&#160; The Joint Patent Committee will meet as often as agreed by them (and at least semi-Annually), to discuss matters arising out of the activities set forth in this 7.1.3.&#160; The
              JPC will determine the JPC operating procedures at its first meeting, including the JPC&#8217;s policies for replacement of JPC members, and the location of meetings, which will be codified in the written minutes of the first JPC meeting.&#160; To the
              extent reasonably requested by either Party, the Joint Patent Committee will solicit the involvement of more senior members of their respective legal departments (up to the most senior intellectual property attorney, where appropriate) with
              respect to critical issues, and may escalate issues to the Executives for input and resolution pursuant to <u>Section 12.1</u>.&#160; Each Party&#8217;s representatives on the Joint Patent Committee will consider comments and suggestions made by the
              other in good faith.&#160; If either Party deems it reasonably advisable, the Parties will enter into a mutually agreeable common interest agreement covering the matters contemplated by this Agreement. Each party shall bear their own cost of
              participation on the JPC.</div>
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          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">7.2</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Prosecution and Maintenance of Patents</u></font><font style="font-size: 10pt;">.</font></div>
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          <td style="width: 36pt; vertical-align: top; font-weight: bold;">7.2.1</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Patent Filings</u></font><font style="font-size: 10pt;">.&#160; The Party responsible for Prosecution and Maintenance of any Patent Rights as set forth in <u>Section
                  7.2.2</u> and <u>Section 7.2.3</u> will endeavor to obtain patent protection for the applicable Product as it Prosecutes and Maintains its other patents Covering products in development, using counsel of its own choice but reasonably
                acceptable to the other Party, in such countries as the responsible Party sees fit.</font></div>
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          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">7.2.2</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Licensed Patents and JBI Patents</u></font><font style="font-size: 10pt;">.</font></div>
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          <td style="width: 36pt; vertical-align: top; font-weight: bold;">(a)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Licensed Patents In General</u></font><font style="font-size: 10pt;">.&#160; Prior to exercise of an Option, Isis will control and be responsible for all aspects of
                the Prosecution and Maintenance of all Licensed Patents that are the subject of such Option, subject to <u>Section 7.2.2(b)</u>, <u>Section 7.2.3</u> and <u>Section 7.2.4</u>.&#160; During the Agreement Term, Isis will control and be
                responsible for all aspects of the Isis Core Technology Patents, Isis Manufacturing and Analytical Patents, and Isis Formulation Patents.</font></div>
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          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">(b)</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Licensed Patents After Option Exercise</u></font><font style="font-size: 10pt;">.&#160; After JBI exercises its Option for a particular Drug Discovery Program, JBI
                will control and be responsible for all aspects of the Prosecution and Maintenance of all Isis Product-Specific Patents and Jointly-Owned Program Patents that cover Products under such Research project to the same extent Isis had the right
                to control and was responsible for such Prosecution and Maintenance immediately prior to such Option exercise, subject to <u>Section 7.2.3</u> and <u>Section 7.2.4</u>, and will grant Isis the license set forth in <u>Section 4.2.2</u>.</font></div>
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          <td style="width: 36pt; vertical-align: top; font-weight: bold;">(c)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>JBI Patents</u></font><font style="font-size: 10pt;">.&#160; JBI will control and be responsible for all aspects of the Prosecution and Maintenance of all JBI
                Patents, subject to <u>Section 7.2.3</u> and <u>Section 7.2.4</u>.</font></div>
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          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">7.2.3</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Jointly-Owned Program Patents</u></font><font style="font-size: 10pt;">.&#160; Isis will control and be responsible for all aspects of the Prosecution and Maintenance
                of Jointly-Owned Program Patents that are not Product Specific Patents.&#160; Prior to exercise of an Option, Isis will control and be responsible for all aspects of the Prosecution and Maintenance of Jointly-Owned Program Patents that are
                Product Specific Patents and the subject of such Option.&#160; After exercise of an Option, JBI will control and be responsible for all aspects of the Prosecution and Maintenance of Jointly-Owned Program Patents that are Product Specific Patents
                and are the subject of such exercised Option.</font></div>
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          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">7.2.4</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Other Matters Pertaining to Prosecution and Maintenance of Patents</u></font><font style="font-size: 10pt;">.</font></div>
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          <td style="width: 36pt; vertical-align: top; font-weight: bold;">(a)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>Each Party will keep the other Party informed through the Joint Patent Committee as to material developments with respect to the Prosecution and Maintenance of the Product-Specific Patents or Jointly-Owned Program Patents for which such
              Party has responsibility for Prosecution and Maintenance pursuant to <u>Section 7.2.2</u>, <u>Section 7.2.3</u> or this <u>Section 7.2.4</u>, including by providing copies of material data as it arises, any office actions or office action
              responses or other correspondence that such Party provides to or receives from any patent office, including notice of all interferences, reissues, re-examinations, oppositions or requests for patent term extensions, and all patent-related
              filings, and by providing the other Party the timely opportunity to have reasonable input into the strategic aspects of such Prosecution and Maintenance.</div>
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          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">(b)</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>If JBI elects (a) not to file and prosecute patent applications for the Jointly-Owned Program Patent Rights or Isis Product-Specific Patents that have been licensed or assigned to JBI under this Agreement or the JBI Product-Specific
              Patents (&#8220;<font style="font-weight: bold; font-style: italic;">JBI-Prosecuted Patents</font>&#8221;) in a particular country, (b) not to continue the prosecution (including any interferences, oppositions, reissue proceedings, re-examinations, and
              patent term extensions, adjustments, and restorations) or maintenance of any JBI-Prosecuted Patent in a particular country, or (c) not to file and prosecute patent applications for the JBI-Prosecuted Patent in a particular country following a
              written request from Isis to file and prosecute in such country, then JBI will so notify Isis promptly in writing of its intention (including a reasonably detailed rationale for doing so) in good time to enable Isis to meet any deadlines by
              which an action must be taken to establish or preserve any such Patent Right in such country; and Isis will have the right, but not the obligation, to file, prosecute, maintain, enforce, or otherwise pursue such JBI-Prosecuted Patent in the
              applicable country at its own expense with counsel of its own choice.&#160; In such case, JBI will cooperate with Isis to file for, or continue to Prosecute and Maintain or enforce, or otherwise pursue such JBI-Prosecuted Patent in such country in
              Isis&#8217; own name, but only to the extent that JBI is not required to take any position with respect to such abandoned JBI-Prosecuted Patent that would be reasonably likely to adversely affect the scope, validity or enforceability of any of the
              other Patent Rights being prosecuted and maintained by JBI under this Agreement.&#160; Notwithstanding anything to the contrary in this Agreement, if Isis assumes responsibility for the Prosecution and Maintenance of any such JBI-Prosecuted Patent
              under this <u>Section 7.2.4(b)</u>, Isis will have no obligation to notify JBI if Isis intends to abandon such JBI-Prosecuted Patent.</div>
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          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">(c)</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>If, during the Agreement Term, Isis intends to abandon any Isis Product-Specific Patent for which Isis is responsible for Prosecution and Maintenance without first filing a continuation or substitution, then, if the applicable Option
              Deadline has not passed, Isis will notify JBI of such intention at least 60 days before such Patent Right will become abandoned, and JBI will have the right, but not the obligation, to assume responsibility for the Prosecution and Maintenance
              thereof at its own expense (subject to <u>Section 7.3.1</u>) with counsel of its own choice.&#160; Notwithstanding anything to the contrary in this Agreement, if JBI assumes responsibility for the Prosecution and Maintenance of any such Isis
              Product-Specific Patent under this <u>Section 7.2.4(c)</u>, JBI will have no obligation to notify Isis if JBI intends to abandon such Isis Product-Specific Patent.</div>
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          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">(d)</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>The Parties, through the Joint Patent Committee, will cooperate in good faith to determine if and when any divisional or continuation applications will be filed with respect to any Program Patents or Product-Specific Patents, and where a
              divisional or continuation patent application filing would be practical and reasonable, then such a divisional or continuation filing will be made.</div>
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          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">(e)</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>If the Party responsible for Prosecution and Maintenance pursuant to <u>Section 7.2.3</u> intends to abandon such Jointly-Owned Program Patent without first filing a continuation or substitution, then such Party will notify the other
              Party of such intention at least 60 days before such Jointly-Owned Program Patent will become abandoned, and such other Party will have the right, but not the obligation, to assume responsibility for the Prosecution and Maintenance thereof at
              its own expense (subject to <u>Section 7.3.1</u>) with counsel of its own choice, in which case the abandoning Party will, and will cause its Affiliates to, assign to the other Party (or, if such assignment is not possible, grant a
              fully-paid exclusive license in) all of their rights, title and interest in and to such Jointly-Owned Program Patents.&#160; If a Party assumes responsibility for the Prosecution and Maintenance of any such Jointly-Owned Program Patents under this
              <u>Section 7.2.4(e)</u>, such Party will have no obligation to notify the other Party of any intention of such Party to abandon such Jointly-Owned Program Patents.</div>
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          <td style="width: 36pt; vertical-align: top; font-weight: bold;">(f)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>In addition, the Parties will consult, through the Joint Patent Committee, and take into consideration the comments of the other Party for all matters relating to interferences, reissues, re-examinations and oppositions with respect to
              those Patent Rights in which such other Party (i) has an ownership interest, (ii) has received a license thereunder in accordance with this Agreement, or (iii) may in the future, in accordance with this Agreement, obtain a license or
              sublicense thereunder.</div>
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          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">7.3</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Patent Costs</u></font><font style="font-size: 10pt;">.</font></div>
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          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">7.3.1</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Jointly-Owned Program Patents</u></font><font style="font-size: 10pt;">.&#160; Unless the Parties agree otherwise, Isis and JBI will share equally the Patent Costs
                associated with the Prosecution and Maintenance of Jointly-Owned Program Patents; <font style="font-style: italic;">provided that,</font> either Party may decline to pay its share of costs for filing, prosecuting and maintaining any
                Jointly-Owned Program Patents in a particular country or particular countries, in which case the declining Party will, and will cause its Affiliates to, assign to the other Party (or, if such assignment is not possible, grant a fully-paid
                exclusive license in) all of their rights, titles and interests in and to such Jointly-Owned Program Patents.</font></div>
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          <td style="width: 36pt; vertical-align: top; font-weight: bold;">7.3.2</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Licensed Patents and JBI Patents</u></font><font style="font-size: 10pt;">.&#160; Except as set forth in <u>Section 7.2.4</u> and <u>Section 7.3.1</u>, each Party
                will be responsible for all Patent Costs incurred by such Party prior to and after the Effective Date in all countries in the Prosecution and Maintenance of Patent Rights for which such Party is responsible under <u>Section 7.2</u>; <font style="font-style: italic;">provided, however</font>, that after Option exercise, JBI will be solely responsible for Patent Costs arising from the Prosecution and Maintenance of the Isis Product-Specific Patents.</font></div>
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          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">7.4</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Defense of Claims Brought by Third </u></font><font style="font-weight: bold; font-size: 10pt;"><u>Parties</u></font><font style="font-size: 10pt;">.</font></div>
          </td>
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          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">7.4.1</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>If a Third Party initiates a Proceeding claiming a Patent Right owned by or licensed to such Third Party is infringed by the Development, Manufacture or Commercialization of a Product, (a) Isis will have the first right, but not the
              obligation, to defend against any such Proceeding initiated prior to Option exercise at its sole cost and expense and (b) JBI will have the first right, but not the obligation, to defend against any such Proceeding initiated after Option
              exercise at its sole cost and expense.&#160; If the Party having the first right to defend against such Proceeding (the &#8220;<font style="font-weight: bold; font-style: italic;">Lead Party</font>&#8221;) elects to defend against such Proceeding, then the
              Lead Party will have the sole right to direct the defense and to elect whether to settle such claim (but only with the prior written consent of the other Party, not to be unreasonably withheld, conditioned or delayed).&#160; The other Party will
              reasonably assist the Lead Party in defending such Proceeding and cooperate in any such litigation at the request and expense of the Lead Party.&#160; The Lead Party will provide the other Party with prompt written notice of the commencement of
              any such Proceeding that is of the type described in this <u>Section 7.4</u>, and the Lead Party will keep the other Party apprised of the progress of such Proceeding. If the Lead Party elects not to defend against a Proceeding, then the
              Lead Party will so notify the other Party in writing within 60 days after the Lead Party first receives written notice of the initiation of such Proceeding, and the other Party (the &#8220;<font style="font-weight: bold; font-style: italic;">Step-In

                Party</font>&#8221;) will have the right, but not the obligation, to defend against such Proceeding at its sole cost and expense and thereafter the Step-In Party will have the sole right to direct the defense thereof, including the right to
              settle such claim.&#160; In any event, the Party not defending such Proceeding will reasonably assist the other Party and cooperate in any such litigation at the request and expense of the Party defending such Proceeding.&#160; Each Party may at its
              own expense and with its own counsel join any defense initiated or directed by the other Party under this <u>Section 7.4</u>.&#160; Each Party will provide the other Party with prompt written notice of the commencement of any such Proceeding
              under this <u>Section 7.4</u>, and such Party will promptly furnish the other Party with a copy of each communication relating to the alleged infringement that is received by such Party.</div>
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          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">7.4.2</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Discontinued Product</u></font><font style="font-size: 10pt;">.&#160; If a Third Party initiates a Proceeding claiming that any Patent Right or Know-How owned by or
                licensed to such Third Party is infringed by the Development, Manufacture or Commercialization of a Discontinued Product, Isis will have the first right, but not the obligation, to defend against and settle such Proceeding at its sole cost
                and expense.&#160; JBI will reasonably assist Isis in defending such Proceeding and cooperate in any such litigation at the request and expense of Isis.&#160; Each Party may at its own expense and with its own counsel join any defense directed by the
                other Party.&#160; Isis will provide JBI with prompt written notice of the commencement of any such Proceeding, or of any allegation of infringement of which Isis becomes aware and that is of the type described in this <u>Section 7.4.2</u>, and
                Isis will promptly furnish JBI with a copy of each communication relating to the alleged infringement received by Isis.</font></div>
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          <td style="width: 36pt; vertical-align: top; font-weight: bold;">7.4.3</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Interplay Between Enforcement of IP and Defense of Third Party Claims</u></font><font style="font-size: 10pt;">. Notwithstanding the provisions of <u>Section
                  7.4.1</u> and <u>Section 7.4.2</u>, to the extent that a Party&#8217;s defense against a Third Party claim of infringement under this <u>Section 7.4</u> involves (i) the enforcement of the other Party&#8217;s Know-How or Patent Rights, or (ii) the
                defense of an invalidity claim with respect to such other Party&#8217;s Know-How or Patent Rights, then, in each case, the general concepts of <u>Section 7.5</u> will apply to the enforcement of such other Party&#8217;s Know-How or Patent Rights or
                the defense of such invalidity claim (<font style="font-style: italic;">i.e.</font>, each Party has the right to enforce its own intellectual property, except that the relevant Commercializing Party will have the initial right, to the
                extent provided in <u>Section 7.5</u>, to enforce such Know-How or Patent Rights or defend such invalidity claim, and the other Party will have a step-in right, to the extent provided in <u>Section 7.5</u>, to enforce such Know-How or
                Patent Rights or defend such invalidity claim).</font></div>
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          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">7.5</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Enforcement of Patents Against Competitive Infringement</u></font><font style="font-size: 10pt;">.</font></div>
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          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">7.5.1</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Duty to Notify of Competitive Infringement</u></font><font style="font-size: 10pt;">.&#160; If either Party learns of an infringement, unauthorized use,
                misappropriation or threatened infringement by a Third Party to which such Party does not owe any obligation of confidentiality with respect to any Product-Specific Patents by reason of the development, manufacture, use or commercialization
                of a product directed against the RNA that encodes a Collaboration Target in the Field (&#8220;<font style="font-weight: bold; font-style: italic;">Competitive</font><font style="font-style: italic;">&#160;</font><font style="font-weight: bold; font-style: italic;">Infringement</font>&#8221;), such Party will promptly notify the other Party in writing and will provide such other Party with available evidence of such Competitive Infringement; <font style="font-style: italic;">provided,


                  however</font>, that for cases of Competitive Infringement under <u>Section 7.5.7</u> below, such written notice will be given within 10 days.</font></div>
          </td>
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    </table>
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          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">7.5.2</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Prior to Option Exercise</u></font><font style="font-size: 10pt;">.&#160; For any Competitive Infringement with respect to a Product occurring after the Effective
                Date but before Option exercise, Isis will have the first right, but not the obligation, to institute, prosecute, and control a Proceeding with respect thereto, by counsel of its own choice, and JBI will have the right to be represented in
                that action by counsel of its own choice at its own expense, <font style="font-style: italic;">however</font>, Isis will have the sole right to control such litigation.&#160; Isis will provide JBI with prompt written notice of the commencement
                of any such Proceeding, and Isis will keep JBI apprised of the progress of such Proceeding.&#160; If Isis fails to initiate a Proceeding within a period of 90 days after receipt of written notice of such Competitive Infringement (subject to a 90
                day extension to conclude negotiations, which extension will apply only in the event that Isis has commenced good faith negotiations with an alleged infringer for elimination of such Competitive Infringement within such 90 day period), JBI
                will have the right to initiate and control a Proceeding with respect to such Competitive Infringement by counsel of its own choice; <font style="font-style: italic;">provided that</font> Isis will have the right to be represented in any
                such action by counsel of its own choice at its own expense.&#160; Notwithstanding the foregoing, Isis will at all times have the sole right to institute, prosecute, and control any Proceeding under this <u>Section 7.5.2</u> to the extent
                involving any the Isis Core Technology Patents, Isis Manufacturing and Analytical Patents, or Isis Formulation Patents.</font></div>
          </td>
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    </table>
    <div>&#160;</div>
    <table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">

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          </td>
          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">7.5.3</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Following Option Exercise</u></font><font style="font-size: 10pt;">.&#160; For any Competitive Infringement with respect to a particular Product (except for a
                Discontinued Product) occurring after Option exercise, so long as part of such Proceeding JBI also enforces any Patent Rights Controlled by JBI being infringed that Cover the Product, then JBI will have the first right, but not the
                obligation, to institute, prosecute, and control a Proceeding to enforce the Isis Product Specific Patents with respect thereto by counsel of its own choice at its own expense, and Isis will have the right, at its own expense, to be
                represented in that action by counsel of its own choice, <font style="font-style: italic;">however,</font> JBI will have the right to control such litigation.&#160; If JBI fails to initiate a Proceeding within a period of 90 days after receipt
                of written notice of such Competitive Infringement (subject to a 90-day extension to conclude negotiations, if JBI has commenced good faith negotiations with an alleged infringer for elimination of such Competitive Infringement within such
                90 day period), Isis will have the right to initiate and control a Proceeding with respect to such Competitive Infringement by counsel of its own choice, and JBI will have the right to be represented in any such action by counsel of its own
                choice at its own expense.&#160; Isis will at all times have the sole right to institute, prosecute, and control any Proceeding under this <u>Section 7.5.3</u> to the extent involving any Isis Core Technology Patents, Isis Manufacturing and
                Analytical Patents, or Isis Formulation Patents.</font></div>
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    </table>
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          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">7.5.4</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Joinder</u></font><font style="font-size: 10pt;">.</font></div>
          </td>
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    </table>
    <div>&#160;</div>
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          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">(a)</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>If a Party initiates a Proceeding in accordance with this <u>Section 7.5</u>, the other Party agrees to be joined as a party plaintiff where necessary and to give the first Party reasonable assistance and authority to file and prosecute
              the Proceeding.&#160; Subject to <u>Section 7.5.5</u>, the costs and expenses of each Party incurred pursuant to this <u>Section 7.5.4(a)</u> will be borne by the Party initiating such Proceeding.</div>
          </td>
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    </table>
    <div>&#160;</div>
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          <td style="width: 36pt; vertical-align: top; font-weight: bold;">(b)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>If one Party initiates a Proceeding in accordance with this <u>Section 7.5.4</u>, the other Party may join such Proceeding as a party plaintiff where necessary for such other Party to seek lost profits with respect to such infringement.</div>
          </td>
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    <div>&#160;</div>
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          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">7.5.5</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Share of Recoveries</u></font><font style="font-size: 10pt;">.&#160; Any damages or other monetary awards recovered with respect to a Proceeding brought pursuant to
                this <u>Section 7.5</u> will be shared as follows:</font></div>
          </td>
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    </table>
    <div>&#160;</div>
    <table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">

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          <td style="width: 63pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">(a)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>the amount of such recovery will first be applied to the Parties&#8217; reasonable Out-of-Pocket Costs incurred in connection with such Proceeding (which amounts will be allocated <font style="font-style: italic;">pro rata</font> if
              insufficient to cover the totality of such expenses); then</div>
          </td>
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    </table>
    <div>&#160;</div>
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          <td style="width: 36pt; vertical-align: top; font-weight: bold;">(b)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>any remaining proceeds constituting direct or actual damages for acts of infringement occurring prior to JBI&#8217;s exercise of the Option will be (i) [***]; or (ii) [***]; then</div>
          </td>
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          <td style="width: 36pt; vertical-align: top; font-weight: bold;">(c)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>any remaining proceeds constituting direct or actual damages for acts of infringement occurring after JBI&#8217;s exercise of the Option [***]; then</div>
          </td>
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    </table>
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    <table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">

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          <td style="width: 36pt; vertical-align: top; font-weight: bold;">(d)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>any remaining proceeds constituting punitive or treble damages will be allocated between the Parties as follows: the Party initiating the Proceeding will receive and retain [***]% of such proceeds and the other Party will receive and
              retain [***]% of such proceeds.</div>
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          <td style="width: 36pt; vertical-align: top; font-weight: bold;">7.5.6</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Settlement</u></font><font style="font-size: 10pt;">.&#160; Notwithstanding anything to the contrary under this Section 7.5.6 neither Party may enter a settlement,
                consent judgment or other voluntary final disposition of a suit under this 7.5.6 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.</font></div>
          </td>
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    </table>
    <div>&#160;</div>
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          </td>
          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">7.5.7</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>35 USC 271(e)(2) Infringement</u></font><font style="font-size: 10pt;">.&#160; Notwithstanding anything to the contrary in this <u>Section 7.5</u>, solely with
                respect to Licensed Patents that have not been assigned to JBI under this Agreement for a Competitive Infringement under 35 USC 271(e)(2), the time period set forth in <u>Section 7.5.2</u> during which a Party will have the initial right
                to bring a Proceeding will be shortened to a total of 25 days, so that, to the extent the other Party has the right, pursuant to such Section to initiate a Proceeding if the first Party does not initiate a Proceeding, such other Party will
                have such right if the first Party does not initiate a Proceeding within 25 days after such first Party&#8217;s receipt of written notice of such Competitive Infringement.</font></div>
          </td>
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    </table>
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          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">7.6</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Other Infringement</u></font><font style="font-size: 10pt;">.</font></div>
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    <div>&#160;</div>
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          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">7.6.1</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Jointly-Owned Program Patents</u></font><font style="font-size: 10pt;">.&#160; With respect to the infringement of a Jointly-Owned Program Patent which is not a
                Competitive Infringement, the Parties will cooperate in good faith to bring suit together against such infringing party or the Parties may decide to permit one Party to solely bring suit.&#160; Any damages or other monetary awards recovered with
                respect to a Proceeding brought pursuant to this <u>Section 7.6.1</u> will be shared as follows: (i) the amount of such recovery will first be applied to the Parties&#8217; reasonable Out-of-Pocket costs incurred in connection with such
                Proceeding (which amounts will be allocated <font style="font-style: italic;">pro rata</font> if insufficient to cover the totality of such expenses); (ii) any remaining proceeds constituting direct damages will be [***], and (iii) any
                remaining proceeds constituting punitive or treble damages will be allocated as follows: (A) if the Parties jointly initiate a Proceeding pursuant to this <u>Section 7.6.1</u>, each Party will receive [***]% of such proceeds; and (B) if
                only one Party initiates the Proceeding pursuant to this <u>Section 7.6.1</u>, such Party will receive [***]% of such proceeds and the other Party will receive [***]% of such proceeds.</font></div>
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    <div>&#160;</div>
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          </td>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">7.6.2</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Patents Solely Owned by Isis</u></font><font style="font-size: 10pt;">.&#160; Isis will retain all rights to pursue an infringement of any Patent Right solely owned
                by Isis which is other than a Competitive Infringement and Isis will retain all recoveries with respect thereto.</font></div>
          </td>
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    </table>
    <div>&#160;</div>
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          </td>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">7.6.3</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Patents Solely Owned by JBI</u></font><font style="font-size: 10pt;">.&#160; JBI will retain all rights to pursue an infringement of any Patent Right solely owned by
                JBI which is other than a Competitive Infringement and JBI will retain all recoveries with respect thereto.</font></div>
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    </table>
    <div>&#160;</div>
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          <td style="width: 36pt; vertical-align: top; font-weight: bold;">7.7</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Patent Listing</u></font><font style="font-size: 10pt;">.&#160; JBI will promptly, accurately and completely list, with the applicable Regulatory Authorities during
                the Agreement Term, all applicable Patent Rights that Cover a Product.&#160; Prior to such listings, the Parties will meet, through the Joint Patent Committee, to evaluate and identify all applicable Patent Rights, and JBI will have the right to
                review, where reasonable, original records relating to any invention for which Patent Rights are being considered by the Joint Patent Committee for any such listing.&#160; Notwithstanding the preceding sentence, JBI will retain final
                decision-making authority as to the listing of all applicable Patent Rights for the Product that are not Isis Core Technology Patents, Isis Manufacturing and Analytical Patents, or Isis Formulation Patents, regardless of which Party owns
                such Patent Rights.</font></div>
          </td>
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    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">7.8</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Joint research agreement under the Leahy-Smith America Invents Act</u></font><font style="font-weight: bold; font-size: 10pt;">.</font><font style="font-size: 10pt;">&#160; In the event that a Party intends to so invoke the Leahy-Smith America Invents Act, once agreed to by the other Party, it will notify the other Party and the Parties shall use reasonable efforts to cooperate and coordinate their
                activities with such Party with respect to any submissions, filings or other activities in support thereof.&#160; The Parties acknowledge and agree that this Agreement is a &#8220;joint research agreement&#8221; as defined in <font style="color: #000000;">35


                  U.S.C. &#167; 100(h)</font></font></div>
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    </table>
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          <td style="width: 36pt; vertical-align: top; font-weight: bold;">7.9</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Obligations to Third Parties</u></font><font style="font-size: 10pt;">.&#160; Notwithstanding any of the foregoing, each Party&#8217;s rights and obligations with respect
                to Licensed Technology under this Section 7.9 will be subject to the Third Party rights and obligations under any (i) New Third Party License the restrictions and obligations of which JBI has agreed to under <u>Section 6.9.2,</u> (ii)
                Prior Agreements, and (iii) Isis In-License Agreements; <font style="font-style: italic;">provided</font>, <font style="font-style: italic;">however</font>, that, to the extent that Isis has a non-transferable right to prosecute, maintain
                or enforce any Patent Rights licensed to JBI hereunder and, this Agreement purports to grant any such rights to JBI, Isis will act in such regard with respect to such Patent Rights at JBI&#8217;s direction.</font></div>
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          <td style="width: 36pt; vertical-align: top; font-weight: bold;">7.10</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Additional Right and Exceptions</u></font><font style="font-size: 10pt;">.&#160; Notwithstanding any provision of this Section 7.10, Isis retains the sole right to
                Prosecute and Maintain Isis Core Technology Patents and Isis Manufacturing and Analytical Patents during the Agreement Term and to control any enforcement of Isis Core Technology Patents and Isis Manufacturing and Analytical Patents, and
                will take the lead on such enforcement solely to the extent that the scope or validity of any Patent Rights Controlled by Isis and Covering the Isis Core Technology Patents or Isis Manufacturing and Analytical Patents is at risk.</font></div>
          </td>
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    </table>
    <div>&#160;</div>
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          <td style="width: 36pt; vertical-align: top; font-weight: bold;">7.11</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Patent Term Extension</u></font><font style="font-weight: bold; font-size: 10pt;">.&#160; </font><font style="font-size: 10pt;">The Parties will cooperate with each
                other in gaining patent term extension wherever applicable to the Product.&#160; After exercising an Option, JBI will determine which relevant patents will be extended.</font></div>
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          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">7.12</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Rights in Bankruptcy.</u></font><font style="font-size: 10pt;">&#160; All rights and licenses granted under or pursuant to any section of this Agreement are and will
                otherwise be deemed to be for purposes of Section 365(n) of Title 11, United States Code (the &#8220;Bankruptcy Code&#8221;) licenses of rights to &#8220;intellectual property&#8221; as defined in Section 101(56) of the Bankruptcy Code.&#160; The Parties will retain
                and may fully exercise all of their respective rights and elections under the Bankruptcy Code.&#160; Upon the bankruptcy of any Party, the non-bankrupt Party will further be entitled to a complete duplicate of, or complete access to, any such
                intellectual property, and such, if not already in its possession, will be promptly delivered to the non-bankrupt Party, unless the bankrupt Party elects in writing to continue, and continues, to perform all of its obligations under this
                Agreement.</font></div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <div style="text-align: center; font-weight: bold;">ARTICLE 8.</div>
    <div style="text-align: center; font-weight: bold;">REPRESENTATIONS AND WARRANTIES</div>
    <div>&#160;</div>
    <table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">8.1</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Representations and Warranties of Both Parties</u></font><font style="font-size: 10pt;">.&#160; Each Party hereby represents and warrants to the other Party, as of
                the Effective Date, that:</font></div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">8.1.1</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>such Party is duly organized, validly existing and in good standing under the laws of the jurisdiction of its incorporation or organization and has full corporate power and authority to enter into this Agreement and to carry out the
              provisions hereof;</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">

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          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">8.1.2</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>such Party has taken all necessary action on its part to authorize the execution and delivery of this Agreement and the performance of its obligations hereunder;</div>
          </td>
        </tr>

    </table>
    &#160;
    <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" id="DSPFPageBreakArea">
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    </div>
    <div>
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            </td>
            <td style="width: 36pt; vertical-align: top; font-weight: bold;">8.1.3</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>this Agreement has been duly executed and delivered on behalf of such Party, and constitutes a legal, valid and binding obligation, enforceable against it in accordance with the terms hereof;</div>
            </td>
          </tr>

      </table>
    </div>
    <div> <br>
    </div>
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          </td>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">8.1.4</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>the execution, delivery and performance of this Agreement by such Party will not constitute a default under or conflict with any agreement, instrument or understanding, oral or written, to which it is a party or by which it is bound, or
              violate any law or regulation of any court, governmental body or administrative or other agency having jurisdiction over such Party;</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">

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          </td>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">8.1.5</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>no government authorization, consent, approval, license, exemption of or filing or registration with any court or governmental department, commission, board, bureau, agency or instrumentality, domestic or foreign, under any applicable
              laws, rules or regulations currently in effect, is or will be necessary for, or in connection with, the transaction contemplated by this Agreement or any other agreement or instrument executed in connection herewith, or for the performance by
              it of its obligations under this Agreement and such other agreements; and</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">

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          </td>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">8.1.6</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>it has not employed (and, to the best of its knowledge, has not used a contractor or consultant that has employed) and in the future will not employ (or, to the best of its knowledge, use any contractor or consultant that employs, provided
              that such Party may reasonably rely on a representation made by such contractor or consultant) any Person debarred by the FDA (or subject to a similar sanction of EMA or foreign equivalent), or any Person which is the subject of an FDA
              debarment investigation or proceeding (or similar proceeding of EMA or foreign equivalent), in the conduct of the Pre-Clinical Studies or Clinical Studies of the Product and its activities under each Drug Discovery Program.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">8.2</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Representations and Warranties of Isis</u></font><font style="font-size: 10pt;">.&#160; Isis hereby represents and warrants to JBI, as of the Effective Date, that:</font></div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">

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          </td>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">8.2.1</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>To the best of its knowledge and belief, there are no additional licenses (beyond those that would be granted to JBI under <u>Section 4.1.1</u> upon the exercise of the Option for a Product arising under the Drug Discovery Programs) under
              any intellectual property owned or Controlled by Isis or its Affiliates as of the Effective Date that would be required in order for JBI to further Develop and Commercialize a Product.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">

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          </td>
          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">8.2.2</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-variant: small-caps; font-size: 10pt;"><u>Schedule </u></font><font style="font-size: 10pt;"><u>8.2.2(a)</u>, <font style="font-variant: small-caps;"><u>Schedule </u></font><u>8.2.2(b),</u>&#160;<font style="font-variant: small-caps;"><u>Schedule </u></font><u>8.2.2(c)</u> and <font style="font-variant: small-caps;"><u>Schedule </u></font><u>8.2.2(d)</u> set forth true, correct and complete lists of all Isis Core Technology Patents,
                Isis Manufacturing and Analytical Patents, and Isis Formulation Patents that apply to the Compounds contemplated under the Drug Discovery Programs as of the Effective Date (the <font style="font-weight: bold; font-style: italic;">&#8220;Isis
                  Platform Technology&#8221;</font>), respectively, and indicates whether each such Patent Right is owned by Isis or licensed by Isis from a Third Party and if so, identifies the licensor or sublicensor from which the Patent Right is licensed.&#160;
                Isis Controls such Patent Rights existing as of the Effective Date and is entitled to grant all rights and licenses (or sublicenses, as the case may be) under such Patent Rights it purports to grant to JBI under this Agreement.</font></div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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      <div style="text-align: center;" id="DSPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;" id="DSPFPageNumber">39</font></div>
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      <div style="width: 100%;" id="DSPFPageHeader">Confidential</div>
    </div>
    <table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">

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          </td>
          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">8.2.3</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>There are no claims, judgments or settlements against or owed by Isis or its Affiliates or pending against Isis or, to the best of Isis&#8217; knowledge, threatened against Isis, in each case relating to the Isis Platform Technology or
              Collaboration Targets that would prevent Isis from performing the activities under this Agreement or from granting JBI the licenses under <u>Section 4.1</u>.&#160; To the best of Isis&#8217; knowledge, there are no claims, judgments or settlements
              against or owed by any Third Party that is party to a Prior Agreement, or pending or threatened claims or litigation against any Third Party that is party to a Prior Agreement, in each case relating to the Isis Platform Technology or
              Collaboration Targets that would prevent Isis from performing the activities under this Agreement or from granting JBI the licenses under <u>Section 4.1</u>.</div>
          </td>
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    </table>
    <div>&#160;</div>
    <table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">

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          </td>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">8.2.4</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>At the Effective Date (a) there is no fact or circumstance known by Isis that would cause Isis to reasonably conclude that any Isis Core Technology Patent or Isis Manufacturing and Analytical Patent is invalid or un-enforceable, (b) there
              is no fact or circumstance known by Isis that would cause Isis to reasonably conclude the inventorship of each Isis Core Technology Patent or Isis Manufacturing and Analytical Patent is not properly identified on each patent, and (c) all
              official fees, maintenance fees and annuities for the Isis Core Technology Patent or Isis Manufacturing and Analytical Patent have been paid.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">

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          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">8.2.5</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>All Isis In-License Agreements are in full force and effect and have not been modified or amended.&#160; Neither Isis nor, to the best knowledge of Isis, the Third Party licensor in an Isis In-License Agreement is in default with respect to a
              material obligation under such Isis In-License Agreement, and neither such party has claimed or has grounds upon which to claim that the other party is in default with respect to a material obligation under, any Isis In-License Agreement.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">

        <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 style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Isis Covenants</u></font><font style="font-size: 10pt;">.&#160; Isis hereby covenants to JBI that, except as expressly permitted under this Agreement:</font></div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">8.3.1</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>Isis will promptly amend <font style="font-variant: small-caps;"><u>Schedule </u></font><u>8.2.2(a)</u>, <font style="font-variant: small-caps;"><u>Schedule </u></font><u>8.2.2(b)</u> and <font style="font-variant: small-caps;"><u>Schedule

                </u></font><u>8.2.2(c)</u> and submit such amended Schedules to JBI if Isis becomes aware that any Isis Core Technology Patents, Isis Manufacturing and Analytical Patents or Isis Product-Specific Patents are not properly identified on such
              Schedule.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">

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          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">8.3.2</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>During the Agreement Term, Isis will maintain and not breach any Isis In-License Agreements and any agreements with Third Parties entered into after the Effective Date (&#8220;<font style="font-weight: bold; font-style: italic;">New Third Party
                Licenses</font>&#8221;) that provide a grant of rights from such Third Party to Isis that are Controlled by Isis and are licensed or that Isis believes may become subject to a license from Isis to JBI for the Development Candidate under this
              Agreement;</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <div>
      <div></div>
    </div>
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      <div style="text-align: center;" id="DSPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;" id="DSPFPageNumber">40</font></div>
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    </div>
    <div>
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            </td>
            <td style="width: 36pt; vertical-align: top; font-weight: bold;">8.3.3</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>Isis will promptly notify JBI of any material breach by Isis or a Third Party of any New Third Party License, and in the event of a breach by Isis, will permit JBI to cure such breach on Isis&#8217; behalf upon JBI&#8217;s request;</div>
            </td>
          </tr>

      </table>
    </div>
    <div> <br>
    </div>
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          </td>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">8.3.4</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>Isis will not amend, modify or terminate any Isis In-License Agreement or New Third Party License in a manner that would adversely affect JBI&#8217;s rights hereunder without first obtaining JBI&#8217;s written consent, which consent may be withheld
              in JBI&#8217;s sole discretion; and</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">

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          </td>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">8.3.5</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>all of Isis&#8217; employees performing activities hereunder on behalf of Isis will be obligated to assign all right, title and interest in and to any inventions developed by them, whether or not patentable, to Isis as the sole owner thereof.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">8.4</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-weight: bold;"><u>DISCLAIMER</u>.&#160; EXCEPT AS OTHERWISE EXPRESSLY SET FORTH IN THIS AGREEMENT, NEITHER PARTY NOR ITS AFFILIATES MAKES ANY REPRESENTATION OR EXTENDS ANY WARRANTY OF ANY KIND, EITHER EXPRESS OR IMPLIED, INCLUDING
              ANY WARRANTY OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE.&#160; JBI AND ISIS UNDERSTAND THAT EACH PRODUCT IS THE SUBJECT OF ONGOING RESEARCH AND DEVELOPMENT AND THAT NEITHER PARTY CAN ASSURE THE SAFETY, USEFULNESS OR COMMERCIAL OR
              TECHNICAL VIABILITY OF EACH PRODUCT.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <div style="text-align: center; font-weight: bold;">ARTICLE 9.</div>
    <div style="text-align: center; font-weight: bold;">INDEMNIFICATION; INSURANCE</div>
    <div>&#160;</div>
    <table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">9.1</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Indemnification by JBI</u></font><font style="font-size: 10pt;">.&#160; JBI will indemnify, defend and hold harmless Isis and its Affiliates, and its or their
                respective directors, officers, employees and agents, from and against any and all liabilities, damages, losses, costs and expenses including the reasonable fees of attorneys (collectively &#8220;<font style="font-weight: bold; font-style: italic;">Losses</font>&#8221;) arising out of or resulting from any and all Third Party suits, claims, actions, proceedings or demands (&#8220;<font style="font-weight: bold; font-style: italic;">Claims</font>&#8221;) based upon:</font></div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">

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          </td>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">9.1.1</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>the gross negligence or willful misconduct of JBI, its Affiliates or Sublicensees and its or their respective directors, officers, employees and agents, in connection with JBI&#8217;s performance of its obligations or exercise of its rights
              under this Agreement;</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">

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          </td>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">9.1.2</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>any breach of any representation or warranty or express covenant made by JBI under <u>ARTICLE 8</u> or any other provision under this Agreement;</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">

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          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">9.1.3</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>the Development or Manufacturing activities that are conducted by or on behalf of JBI or its Affiliates or Sublicensees; or</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">

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          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">9.1.4</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>the Commercialization of a Product by or on behalf of JBI or its Affiliates or Sublicensees;</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt; margin-left: 36pt;">except, in each case above, to the extent such Claim arose out of or resulted from or is attributable to any acts or omissions of Isis or its Affiliates, licensees, Sublicensees or
      contractors, and its or their respective directors, officers, employees and agents or other circumstance in each case for which Isis has an indemnity obligation pursuant to <u>Section 9.2</u>.</div>
    <div>&#160;</div>
    <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" id="DSPFPageBreakArea">
      <div style="text-align: center;" id="DSPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;" id="DSPFPageNumber">41</font></div>
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    </div>
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          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">9.2</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Indemnification by Isis</u></font><font style="font-size: 10pt;">.&#160; Isis will indemnify, defend and hold harmless JBI and its Affiliates, and its or their
                respective directors, officers, employees and agents, from and against any and all Losses arising out of or resulting from any and all Claims based upon:</font></div>
          </td>
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    <div>&#160;</div>
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          </td>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">9.2.1</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>the gross negligence or willful misconduct of Isis, its Affiliates or Sublicensees or its or their respective directors, officers, employees and agents, in connection with Isis&#8217; performance of its obligations or exercise of its rights
              under this Agreement;</div>
          </td>
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    </table>
    <div>&#160;</div>
    <table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">

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          </td>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">9.2.2</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>any breach of any representation or warranty or express covenant made by Isis under <u>ARTICLE 8</u> or any other provision under this Agreement; or</div>
          </td>
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    <div>&#160;</div>
    <table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">

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          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">9.2.3</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>any development, manufacturing or commercialization activities that are conducted by or on behalf of Isis or its Affiliates or Sublicensees with respect to a Discontinued Product.</div>
          </td>
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    </table>
    <div>&#160;</div>
    <div style="text-align: justify; margin-left: 72pt;">except, in each case above, to the extent such Claim arose out of or resulted from or is attributable to any acts or omissions of JBI or its Affiliates, licensees, Sublicensees or contractors and its
      or their respective directors, officers, employees and agents or other circumstance, in each case for which JBI has an indemnity obligation pursuant to <u>Section 9.1</u>.</div>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">9.3</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Procedure</u></font><font style="font-size: 10pt;">.&#160; If a Person entitled to indemnification under <u>Section 9.1</u> or <u>Section 9.2</u> (an &#8220;<font style="font-weight: bold; font-style: italic;">Indemnitee</font>&#8221;) seeks such indemnification, such Indemnitee will (i) inform the indemnifying Party in writing of a Claim as soon as reasonably practicable after such Indemnitee receives
                notice of such Claim, (ii) permit the indemnifying Party to assume direction and control of the defense of the Claim (including the sole right to settle such Claim at the sole discretion of the indemnifying Party, <font style="font-style: italic;">provided that</font> (A) such settlement or compromise does not admit any fault or negligence on the part of the Indemnitee, or impose any obligation on, or otherwise materially adversely affect, the Indemnitee or other Party and
                (B) the indemnifying Party first obtain the written consent of the Indemnitee with respect to such settlement, which consent will not be unreasonably withheld), (iii) cooperate as reasonably requested (at the expense of the indemnifying
                Party) in the defense of the Claim, and (iv) undertake reasonable steps to mitigate any Losses with respect to the Claim.&#160; The provisions of <u>Section 7.4</u> will govern the procedures for responding to a Claim of infringement described
                therein.&#160; Notwithstanding anything in this Agreement to the contrary, the indemnifying Party will have no liability under <u>Section 9.1</u> or <u>Section 9.2</u>, as the case may be, for Claims settled or compromised by the Indemnitee
                without the indemnifying Party&#8217;s prior written consent.</font></div>
          </td>
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    <div>&#160;</div>
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          <td style="width: 36pt; vertical-align: top; font-weight: bold;">9.4</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Insurance</u></font><font style="font-size: 10pt;">.</font></div>
          </td>
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    <div>&#160;</div>
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          </td>
          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">9.4.1</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Isis&#8217; Insurance Obligations</u></font><font style="font-size: 10pt;">.&#160; Isis will maintain, at its cost, reasonable insurance against liability and other risks
                associated with its activities contemplated by this Agreement.</font></div>
          </td>
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    </table>
    <div>&#160;</div>
    <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" id="DSPFPageBreakArea">
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          </td>
          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">9.4.2</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>JBI&#8217;s Insurance Obligations</u></font><font style="font-size: 10pt;">.&#160; JBI will maintain, at its cost, reasonable insurance against liability and other risks
                associated with its activities contemplated by this Agreement, <font style="font-style: italic;">provided, that</font>, at a minimum, JBI will maintain, in force from [***] days prior to enrollment of the first patient in a Clinical Study,
                a clinical trials/product liability insurance policy providing coverage of at least $[***] per claim and $[***] Annual aggregate and, <font style="font-style: italic;">provided further</font> that such coverage is increased to at least
                $[***] at least [***] days before JBI initiates the First Commercial Sale of a Product hereunder.&#160; JBI will furnish to Isis evidence of such insurance upon request.&#160; Notwithstanding the foregoing, JBI may self-insure to the extent that it
                self-insures for its other products, but at a minimum will self-insure at levels that are consistent with levels customarily maintained against similar risks by similar companies in JBI&#8217;s industry.</font></div>
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    <div>&#160;</div>
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          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">9.5</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-weight: bold;"><u>LIMITATION OF CONSEQUENTIAL DAMAGES</u>.&#160; EXCEPT FOR (a) CLAIMS OF A THIRD PARTY THAT ARE SUBJECT TO INDEMNIFICATION UNDER THIS <u>ARTICLE 9</u>, (b) CLAIMS ARISING OUT OF A PARTY&#8217;S WILLFUL MISCONDUCT UNDER
              THIS AGREEMENT, (c) A PARTY&#8217;S BREACH OF <u>ARTICLE 2</u>, OR A BREACH OF <u>SECTION 10.3.4(a)</u> BY JBI OR ITS AFFILIATES OR (d) CLAIMS ARISING OUT OF A PARTY&#8217;S BREACH OF ITS CONFIDENTIALITY OBLIGATIONS UNDER THIS AGREEMENT, NEITHER PARTY
              NOR ANY OF ITS AFFILIATES WILL BE LIABLE TO THE OTHER PARTY TO THIS AGREEMENT OR ITS AFFILIATES FOR ANY INCIDENTAL, CONSEQUENTIAL, SPECIAL, PUNITIVE OR OTHER INDIRECT DAMAGES OR LOST OR IMPUTED PROFITS OR ROYALTIES, LOST DATA OR COST OF
              PROCUREMENT OF SUBSTITUTE GOODS OR SERVICES, WHETHER LIABILITY IS ASSERTED IN CONTRACT, TORT (INCLUDING NEGLIGENCE AND STRICT PRODUCT LIABILITY), INDEMNITY OR CONTRIBUTION, AND IRRESPECTIVE OF WHETHER THAT PARTY OR ANY REPRESENTATIVE OF THAT
              PARTY HAS BEEN ADVISED OF, OR OTHERWISE MIGHT HAVE ANTICIPATED THE POSSIBILITY OF, ANY SUCH LOSS OR DAMAGE.</div>
          </td>
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    </table>
    <div>&#160;</div>
    <div style="text-align: center; font-weight: bold;">ARTICLE 10.</div>
    <div style="text-align: center; font-weight: bold;">TERM; TERMINATION</div>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">10.1</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Agreement Term; Expiration</u></font><font style="font-size: 10pt;">.&#160; This Agreement is effective as of the Effective Date and, unless earlier terminated
                pursuant to the other provisions of this <u>ARTICLE 10</u>, will continue in full force and effect until the expiration of all payment obligations under this Agreement with respect to all Products in all countries; <font style="font-style: italic;">provided, however,</font> that if every Option either (a) has expired as a result of JBI not providing Isis a written notice stating JBI is exercising such Option and paying Isis the applicable license fee
                under <u>Section 6.4</u> by the applicable Option Deadline, or (b) has been terminated prior to Option exercise pursuant to <u>Section 10.2.1</u> or <u>10.2.2</u>, then this Agreement will expire on the expiration or termination, as
                applicable, of the last Option.</font></div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <div style="text-align: justify; margin-left: 36pt;">The period from the Effective Date until the date of expiration of this Agreement pursuant to this <u>Section 10.1</u> is the &#8220;<font style="font-weight: bold; font-style: italic;">Agreement Term</font>.&#8221;</div>
    <div>&#160;</div>
    <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" id="DSPFPageBreakArea">
      <div style="text-align: center;" id="DSPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;" id="DSPFPageNumber">43</font></div>
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          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">10.2</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Termination of the Agreement</u></font><font style="font-size: 10pt;">.</font></div>
          </td>
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    <div>&#160;</div>
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          </td>
          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">10.2.1</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>JBI&#8217;s Termination for Convenience</u></font><font style="font-size: 10pt;">.&#160; At any time following payment by JBI of the upfront fee under <u>Section 6.1</u>,
                subject to <u>Section 10.3.1</u> below, JBI will be entitled to terminate this Agreement as a whole, or terminate this Agreement in part with respect to a particular Drug Discovery Program and applicable Collaboration Target, for
                convenience by providing 90 days written notice to Isis of such termination.</font></div>
          </td>
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    <div>&#160;</div>
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          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">10.2.2</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Termination for Material Breach</u></font><font style="font-size: 10pt;">.</font></div>
          </td>
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    <div>&#160;</div>
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          </td>
          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">(a)</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>JBI&#8217;s Right to Terminate</u></font><font style="font-size: 10pt;">.&#160; If JBI believes that Isis is in material breach of this Agreement (other than with respect
                to a failure to use Commercially Reasonable Efforts under <u>Section 1.2.5</u>, which is governed by <u>Section 10.2.3</u> below), then JBI may deliver notice of such material breach to Isis.&#160; If the breach is curable, Isis will have 60
                days to cure such breach.&#160; If Isis fails to cure such breach within the 60 day period, or if the breach is not subject to cure, JBI may terminate this Agreement as a whole, or terminate this Agreement in part with respect to the particular
                Program affected by such breach, and the applicable Collaboration Target, by providing written notice to Isis.&#160; Without limiting the foregoing, breach by a Party of <u>ARTICLE 2</u> of this Agreement constitutes a material breach of this
                Agreement with respect to the Program affected by such breach and the applicable Collaboration Target.</font></div>
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    <div>&#160;</div>
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          </td>
          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">(b)</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Isis&#8217; Right to Terminate</u></font><font style="font-size: 10pt;">.&#160; If Isis believes that JBI is in material breach of this Agreement (other than with respect
                to a failure to use Commercially Reasonable Efforts under <u>Section 1.2.5</u>, <u>Section 5.1</u> or <u>Section 5.2</u>, which is governed by <u>Section 10.2.3</u> below), then Isis may deliver notice of such material breach to JBI.&#160;
                If the breach is curable, JBI will have 60 days to cure such breach (except to the extent such breach involves the failure to make a payment when due, which breach must be cured within 30 days following such notice).&#160; If JBI fails to cure
                such breach within the 60 day or 30 day period, as applicable, or if the breach is not subject to cure, Isis in its sole discretion may terminate this Agreement with respect to the Drug Discovery Program(s) and the applicable Collaboration
                Target(s) affected by such breach by providing written notice thereof to JBI.&#160; To the extent such material breach is uncured for one Drug Discovery Program, the remaining active Drug Discovery Programs for which there is no uncured material
                breach shall remain in effect.</font></div>
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    </table>
    <div>&#160;</div>
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          </td>
          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">10.2.3</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Remedies for Failure to Use Commercially Reasonable Efforts</u></font><font style="font-size: 10pt;">.</font></div>
          </td>
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    <div>&#160;</div>
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          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">(a)</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>If Isis, in JBI&#8217;s reasonable determination, fails to use Commercially Reasonable Efforts in the activities contemplated in <u>Section 1.2.5</u> prior to Option exercise with respect to a particular Drug Discovery Program or with respect
              to other agreed-upon activities to be performed by Isis associated with the research, Development, or Commercialization of a Product, under this Agreement, JBI will notify Isis and, within 30 days thereafter, Isis and JBI will meet and confer
              to discuss and resolve the matter in good faith, and attempt to devise a mutually agreeable plan to address any outstanding issues related to Isis&#8217; use of Commercially Reasonable Efforts in <u>Section 1.2.5</u> or for activities otherwise
              agreed upon by Isis under this Agreement.&#160; Following such a meeting, if Isis fails to use Commercially Reasonable Efforts as contemplated by <u>Section 1.2.5</u> with respect to such Drug Discovery Program, then subject to <u>Section 10.2.4</u>
              below, JBI will have the right to terminate this Agreement as it relates to the applicable&#160; Drug Discovery Program.</div>
          </td>
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    <div>&#160;</div>
    <table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">

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          </td>
          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">(b)</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>If JBI, in Isis&#8217; reasonable determination, fails to use Commercially Reasonable Efforts under <u>Section 1.2.5</u>, <u>Section 5.1</u> or <u>Section 5.2 </u>with respect to a Product or Drug Discovery Program above, Isis will notify
              JBI and, within 30 days thereafter, Isis and JBI will meet and confer to discuss and resolve the matter in good faith, and attempt to devise a mutually agreeable plan to address any outstanding issues related to JBI&#8217;s use of Commercially
              Reasonable Efforts in <u>Section 1.2.5</u>, <u>Section 5.1</u> or <u>Section 5.2</u>.&#160; Following such a meeting, if JBI fails to use Commercially Reasonable Efforts with respect to the applicable Product or Drug Discovery Program as
              contemplated by <u>Section 1.2.5</u>, <u>Section 5.1</u> or <u>Section 5.2</u>, then subject to <u>Section 10.2.4</u> below, Isis will have the right, at its sole discretion, to terminate this Agreement as it relates to such Product or
              Drug Discovery Program.</div>
          </td>
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    </table>
    <div>&#160;</div>
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          </td>
          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">10.2.4</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Disputes Regarding Material Breach</u></font><font style="font-size: 10pt;">.&#160; Notwithstanding the foregoing, if the Breaching Party in <u>Section 10.2.2</u> or
                <u>Section 10.2.3</u> disputes in good faith the existence, materiality, or failure to cure of any such breach which is not a payment breach, and provides notice to the Non-Breaching Party of such dispute within such 60 day period, the
                Non-Breaching Party will not have the right to terminate this Agreement in accordance with <u>Section 10.2.2</u> or <u>Section 10.2.3</u>, as applicable, unless and until it has been determined in accordance with <u>Section 12.1</u> that
                this Agreement was materially breached by the Breaching Party and the Breaching Party fails to cure such breach within 30 days following such determination.&#160; It is understood and acknowledged that during the pendency of such dispute, all
                the terms and conditions of this Agreement will remain in effect and the Parties will continue to perform all of their respective obligations hereunder, including satisfying any payment obligations.</font></div>
          </td>
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    <div>&#160;</div>
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          </td>
          <td style="width: 36pt; vertical-align: top;"><font style="font-weight: bold;">10.2.5</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Termination for Patent Challenge</u></font><font style="font-size: 10pt;">.&#160; Isis may terminate this Agreement, if JBI disputes, [***] validity [***], provided
                however that, [***] Isis shall not have the right to terminate if [***]:</font></div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <div style="text-align: justify; margin-left: 72pt;">(a) JBI asserts invalidity as a defense in any court proceeding bought by Isis asserting infringement of a granted Patent within the Isis Core Technology Patents, Isis Manufacturing and Analytical
      Patents, or [***]; or</div>
    <div>&#160;</div>
    <div style="text-align: justify; margin-left: 72pt;">(b) JBI (i) acquires a Third Party that has an existing challenge, whether in a court or administrative proceeding, against a granted Patent within the Isis Core Technology Patents, Isis
      Manufacturing and Analytical Patents, or Isis Formulation Patents or (ii) licenses a product for which Isis has an existing challenge, whether in a court or administrative proceeding, against [***].</div>
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            <td style="width: 36pt; vertical-align: top; font-weight: bold;">10.2.6</td>
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              <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Termination for Insolvency</u></font><font style="font-size: 10pt;">. Either Party may terminate this Agreement if, at any time, the other Party files in any
                  court or agency pursuant to any statute or regulation of any state or country a petition in bankruptcy or insolvency or for reorganization or for an arrangement or for the appointment of a receiver or trustee of the Party or of
                  substantially all of its assets; or if the other Party proposes a written agreement of composition or extension of substantially all of its debts; or if the other Party will be served with an involuntary petition against it, filed in any
                  insolvency proceeding, and such petition will not be dismissed within 90 days after the filing thereof; or if the other Party will propose or be a party to any dissolution or liquidation; or if the other Party will make an assignment of
                  substantially all of its assets for the benefit of creditors.</font></div>
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              <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Consequences of Expiration or Termination of the Agreement</u></font><font style="font-size: 10pt;">.</font></div>
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            <td style="width: 36pt; vertical-align: top;"><a name="z_Ref311053565"></a><a name="z_Ref309574338"></a><a name="z_Ref305050864"></a><font style="font-weight: bold;">10.3.1</font></td>
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              <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>In General</u></font><font style="font-size: 10pt;">.&#160; If this Agreement expires or is terminated by a Party in accordance with this <u>ARTICLE 10</u> at any
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      <div>&#160;</div>
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              <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Return of Information and Materials</u></font><font style="font-size: 10pt;">.&#160; The Parties will return (or destroy, as directed by the other Party) all data,
                  files, records and other materials containing or comprising the other Party&#8217;s Confidential Information, except to the extent such Confidential Information is necessary or useful to conduct activities under a surviving Drug Discovery
                  Program.&#160; Notwithstanding the foregoing, the Parties will be permitted to retain one copy of such data, files, records, and other materials for archival and legal compliance purposes.</font></div>
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            <td style="width: 36pt; vertical-align: top;"><a name="z_Ref243720065"></a><a name="z_Ref253666874"></a><a name="z_Ref309575432"></a><font style="font-weight: bold;">(b)</font></td>
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              <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Accrued Rights</u></font><font style="font-size: 10pt;">.&#160; Termination or expiration of this Agreement for any reason will be without prejudice to any rights
                  or financial compensation that will have accrued to the benefit of a Party prior to such termination or expiration.&#160; Such termination or expiration will not relieve a Party from obligations that are expressly indicated to survive the
                  termination or expiration of this Agreement.&#160; For purposes of clarification, milestone payments under <u>ARTICLE 6</u> accrue as of the date the applicable Milestone Event is achieved even if the payment is not due at that time.</font></div>
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      <div>&#160;</div>
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            <td style="width: 36pt; vertical-align: top;"><a name="z_Ref253666879"></a><font style="font-weight: bold;">(c)</font></td>
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              <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Survival</u></font><font style="font-size: 10pt;">.&#160; The following provisions of this Agreement will survive the expiration or termination of this Agreement: <u>Section



                    4.1.2(c)</u> (Effect of Termination on Sublicenses), <u>Section 4.2.2</u>, <u>Section 6.11.3</u> (Records Retention), <u>Section 6.12</u> (Audits), <u>Section 7.1.1</u> (Isis Technology and JBI Technology), <u>Section 7.1.2</u>
                  (Agreement Technology), <u>Section 8.4</u> (Disclaimer), <u>ARTICLE 9</u> (Indemnification; Insurance), <u>Section 10.2.5</u> (Termination for Insolvency), <u>Section 10.3</u> (Consequences of Expiration or Termination of the
                  Agreement), <u>ARTICLE 11</u> (Confidentiality), <u>ARTICLE 12</u> (Miscellaneous) and <font style="font-variant: small-caps;"><u>Appendix 1</u></font> (Definitions) (to the extent definitions are embodied in the foregoing listed
                  Articles and Sections).</font></div>
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              <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Perpetual, Royalty-Free Non-Exclusive License</u></font><font style="font-size: 10pt;">.&#160; If JBI has exercised its Option for a particular Drug Discovery
                  Program, then upon expiration of the Royalty Period in all countries in which the applicable Products are being or have been sold, Isis will and hereby does grant to JBI a perpetual, nonexclusive, worldwide, royalty-free, fully paid-up,
                  sublicensable license under the Isis Know-How to Manufacture, Develop and Commercialize any Product under such Drug Discovery Program.</font></div>
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      <div>&#160;</div>
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            <td style="width: 36pt; vertical-align: top; font-weight: bold;">10.3.3</td>
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              <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Termination Before Option Exercise</u></font><font style="font-size: 10pt;">.&#160; If this Agreement expires or is terminated by a Party in accordance with this <u>ARTICLE



                    10</u> before Option exercise, then, in addition to the terms set forth in <u>Section 10.3.1</u>, the following terms will apply to each Drug Discovery Program that is the subject of such expiration or termination:</font></div>
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      <div>&#160;</div>
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              <div>JBI&#8217;s Option under <u>Section 3.1</u> will expire and Isis will be free to Develop and Commercialize Compounds included in such Drug Discovery Program on its own or with a Third Party.</div>
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      <div>&#160;</div>
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              <div>Neither Party will have any further obligations under <u>Section 2.1</u> of this Agreement with respect to the terminated Drug Discovery Program(s).</div>
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      <div>&#160;</div>
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              <div>To the extent requested by Isis, JBI will promptly transfer to Isis all data, results and information (including JBI&#8217;s Confidential Information and any regulatory documentation (including drafts)) related to the terminated Drug Discovery
                Program(s) in the possession of JBI and its contractors to the extent such data, results and information were generated by or on behalf of JBI under this Agreement.</div>
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      <div>&#160;</div>
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              <div>Except as explicitly set forth in <u>Section 10.3.1(a)</u>, <u>Section 10.3.1(b)</u> or <u>Section 10.3.1(c)</u>, JBI will have no further rights and Isis will have no further obligations with respect to each terminated Drug Discovery
                Program.</div>
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      <div>&#160;</div>
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              <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Termination After Option Exercise</u></font><font style="font-size: 10pt;">.&#160; If this Agreement is terminated by a Party in accordance with this <u>ARTICLE 10</u>
                  after Option exercise, then, in addition to the terms set forth in <u>Section 10.3.1</u>, the following terms will apply to any Pre-Clinical Development Program that is the subject of such termination:</font></div>
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      <div>&#160;</div>
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              <div>The applicable licenses granted by Isis to JBI under this Agreement will terminate and JBI, its Affiliates and Sublicensees will cease selling the applicable Products.</div>
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              <div>Neither Party will have any further obligations under <u>Section 2.1</u> of this Agreement with respect to the terminated Pre-Clinical Development Program(s).</div>
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      <div>&#160;</div>
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              <div>Except as explicitly set forth in <u>Section 10.3.1(a)</u>, JBI will have no further rights and Isis will have no further obligations with respect to the terminated Pre-Clinical Development Program.</div>
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      <div>&#160;</div>
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            <td style="width: 36pt; vertical-align: top; font-weight: bold;">(d)</td>
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              <div>If (y) JBI terminates the Agreement under <u>Section 10.2.1</u> (JBI&#8217;s Termination for Convenience) or (z) Isis terminates this Agreement under <u>Section 10.2.2(b)</u> (Isis&#8217; Right to Terminate) or <u>Section 10.2.3</u> (Remedies for
                Failure to Use Commercially Reasonable Efforts), then the following additional terms will also apply <font style="font-style: italic;">solely with respect to the terminated </font>Pre-<font style="font-style: italic;">Clinical Development
                  Program(s)</font>:</div>
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      <div>&#160;</div>
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            <td style="width: 36pt; vertical-align: top; font-weight: bold;">(i)</td>
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              <div>JBI will grant to Isis a sublicensable, worldwide, royalty bearing exclusive license or sublicense, as the case may be, to all JBI Technology Controlled by JBI as of the date of such reversion that Covers the applicable Discontinued
                Product(s) solely as necessary to Develop, make, have made, use, sell, offer for sale, have sold, import and otherwise Commercialize the applicable Discontinued Product(s) in the Field (such license will be sublicensable by Isis in
                accordance with <u>Section 4.1.2</u>, <font style="font-style: italic;">mutatis mutandis</font>);</div>
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      <div>&#160;</div>
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            <td style="width: 108pt;"><br>
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              <div>For each Discontinued Product for which JBI, its Affiliate or Sublicensee has [***], Isis or any sublicensee or collaborator shall pay to JBI a royalty on net sales made by Isis or its Affiliates or sublicensee of such Discontinued
                Product according to the following: (a) if neither [***] prior to termination: [***]% of Net Sales, (b) if JBI, its Affiliate or Sublicensee [***] for such Discontinued Product prior to termination: [***]% of Net Sales, (c) if JBI, its
                Affiliate or Sublicensee [***] for such Discontinued Product prior to termination: [***]% of Net Sales, and (d) if JBI, its Affiliate or Sublicensee [***] for such Discontinued Product prior to termination: [***]% of Net Sales; <u>provided</u>
                (A) if (i) Isis enters an arms-length license agreement with a Third Party with respect to a Discontinued Product and (ii) the definition of Net Sales is different in such license agreement than as described above, then, the Parties will
                use the definition described in the Third Party license for the calculation of royalties under this <u>Section 10.3.4(d)(ii)</u>; and (B) <u>Sections 6.8.2, 6.10, 6.12</u> and <u>6.14</u> will govern the payment of royalties from Isis to
                JBI under this <u>Section 10.3.4(d)(ii)</u>, <font style="font-style: italic;">mutatis mutandis</font>.</div>
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      <div>&#160;</div>
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            <td style="width: 36pt; vertical-align: top; font-weight: bold;">(iii)</td>
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              <div>JBI will assign to Isis any Product-Specific Patent Rights and Isis&#8217; interest in any Jointly-Owned Program Patents that, in each case relate to the applicable Discontinued Product(s) previously assigned by Isis to JBI under this
                Agreement;</div>
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      </div>
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            <td style="width: 36pt; vertical-align: top; font-weight: bold;">(iv)</td>
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              <div>JBI will transfer to Isis for use with respect to the Development and Commercialization of the applicable Discontinued Product(s), any Know-How data, results, regulatory information, filings, and files in the possession of JBI as of the
                date of such reversion to the extent related to such Discontinued Product(s), and any other information or material specified in <u>Section 4.4</u>;</div>
            </td>
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      <div>&#160;</div>
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            <td style="width: 36pt; vertical-align: top; font-weight: bold;">(v)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>JBI will license to Isis any trademarks that are specific to a Discontinued Product(s) solely for use with such Discontinued Product(s), in accordance with <u>Section 4.1.5</u>, <font style="font-style: italic;">mutatis mutandis</font>;
                <font style="font-style: italic;">provided, however</font>, that in no event will JBI have any obligation to license to Isis any trademarks used by JBI both in connection with the Product and in connection with the sale of any other product
                or service, including any JBI- or JBI-formative marks; and</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table id="z5e6a28ee0a0c4a66a4dd1c621e65fb45" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

          <tr>
            <td style="width: 108pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top; font-weight: bold;">(vi)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>Isis will control and be responsible for all aspects of the Prosecution and Maintenance of all Jointly-Owned Program Patents arising from the terminated Pre-Clinical Development Program (or the corresponding Drug Discovery Program), and
                JBI will provide Isis with (and will instruct its counsel to provide Isis with) all of the information and records in JBI&#8217;s and its counsel&#8217;s possession related to the Prosecution and Maintenance of such Jointly-Owned Program Patents; <font style="font-style: italic;">provided, however</font>, if Isis intends to abandon any such Jointly-Owned Program Patents without first filing a continuation or substitution, then Isis will notify JBI of such intention at least 60 days
                before such Patent Right will become abandoned, and JBI will have the right, but not the obligation, to assume responsibility for the Prosecution and Maintenance thereof at its own expense with counsel of its own choice.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table id="z1bee4a0fb95547b9aea7ec6b9adb442b" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

          <tr>
            <td style="width: 72pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top; font-weight: bold;">(e)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>If Isis terminates this Agreement due to JBI&#8217;s material breach or JBI terminates this Agreement for convenience, upon Isis&#8217; written request pursuant to a mutually agreed supply agreement, JBI will sell to Isis any bulk API, Clinical
                Supplies and Finished Drug Product in JBI&#8217;s possession at the time of such termination, at a price equal to JBI&#8217;s cost at the time of manufacture.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table id="z26e07c56b6984476b9a2b7642b4de76e" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

          <tr>
            <td style="width: 72pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top; font-weight: bold;">(f)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>To the extent requested by Isis, JBI will promptly assign to Isis any manufacturing agreements identified by Isis solely to the extent related to the applicable Discontinued Products to which JBI is a party.</div>
            </td>
          </tr>

      </table>
      <div> <br>
      </div>
      <div id="DSPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
        <div id="DSPFPageNumberArea" style="text-align: center;"><font id="DSPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">49</font></div>
        <div id="DSPFPageBreak" style="page-break-after: always;">
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      <div style="text-align: center; font-weight: bold;"><a name="z_Ref243449453"></a><a name="z_Ref254872630"></a>ARTICLE 11.</div>
      <div style="text-align: center; font-weight: bold;">CONFIDENTIALITY</div>
      <div>&#160;</div>
      <table id="z8c150251e9664b5d80229cc7ba6103d6" class="DSPFListTable" style="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;"><a name="z_Ref243282675"></a><font style="font-weight: bold;">11.1</font></td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Confidentiality; Exceptions</u></font><font style="font-size: 10pt;">.&#160; Except to the extent expressly authorized by this Agreement or otherwise agreed in
                  writing, the Parties agree that, during the Agreement Term and for five years thereafter, the receiving Party (the &#8220;<font style="font-weight: bold; font-style: italic;">Receiving Party</font>&#8221;) and its Affiliates will keep confidential
                  and will not publish or otherwise disclose or use for any purpose other than as provided for in this Agreement any confidential or proprietary information or materials, patentable or otherwise, in any form (written, oral, photographic,
                  electronic, magnetic, or otherwise) which is disclosed to it by the other Party (the &#8220;<font style="font-weight: bold; font-style: italic;">Disclosing Party</font>&#8221;) or its Affiliates or otherwise received or accessed by a Receiving Party
                  in the course of performing its obligations or exercising its rights under this Agreement, including trade secrets, Know-How, inventions or discoveries, proprietary information, formulae, processes, techniques and information relating to
                  the past, present and future marketing, financial, and research and development activities of any product or potential product or useful technology of the Disclosing Party or its Affiliates and the pricing thereof (collectively, &#8220;<font style="font-weight: bold; font-style: italic;">Confidential Information</font>&#8221;).</font></div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table id="zfade113bfc1e459a8aedff022cb0540d" class="DSPFListTable" style="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;"><a name="z_Ref243203476"></a><font style="font-weight: bold;">11.2</font></td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Prior Confidentiality Agreement Superseded</u></font><font style="font-size: 10pt;">.&#160; As of the Effective Date, this Agreement supersedes the Confidential
                  Disclosure Agreement executed by Isis and JBI on July 30, 2014 (including any and all amendments thereto).&#160; All information exchanged between the Parties under such Confidential Disclosure Agreement will be deemed Confidential Information
                  hereunder and will be subject to the terms of this <u>ARTICLE 11</u>.</font></div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table id="zf96f4581458a459aa4058fb34abb6ff1" class="DSPFListTable" style="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;"><a name="z_Ref323742403"></a><font style="font-weight: bold;">11.3</font></td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Authorized Disclosure</u></font><font style="font-size: 10pt;">.&#160; Except as expressly provided otherwise in this Agreement, a Receiving Party or its Affiliates
                  may use and disclose to Third Parties Confidential Information of the Disclosing Party as follows: (i) solely in connection with the performance of its obligations or exercise of rights granted or reserved in this Agreement under
                  confidentiality provisions no less restrictive than those in this Agreement, <font style="font-style: italic;">provided,</font> that Confidential Information may be disclosed by a Receiving Party to a governmental entity or agency
                  without requiring such entity or agency to enter into a confidentiality agreement; (ii) to the extent reasonably necessary to file or prosecute patent, copyright and trademark applications (subject to <u>Section 11.4</u> below),
                  complying with applicable governmental regulations, obtaining Approvals, conducting Pre-Clinical Studies or Clinical Studies, marketing the Product, or as otherwise required by applicable law, regulation, rule or legal process (including
                  the rules of the SEC and any stock exchange); <font style="font-style: italic;">provided, however</font>, that if a Receiving Party or any of its Affiliates is required by law or regulation to make any such disclosure of a Disclosing
                  Party&#8217;s Confidential Information it will, except where impracticable for necessary disclosures, give reasonable advance notice to the Disclosing Party of such disclosure requirement and will use its reasonable efforts to secure
                  confidential treatment of such Confidential Information required to be disclosed; (iii) in communication with actual or potential lenders, investors, merger partners, acquirers, consultants, or professional advisors on a need-to-know
                  basis, in each case under confidentiality provisions no less restrictive than those of this Agreement; (iv) to the extent such disclosure is required to comply with existing expressly stated contractual obligations owed to such Party&#8217;s or
                  its Affiliates&#8217; licensor with respect to any intellectual property licensed to the other Party under this Agreement; or (v) as mutually agreed to in writing by the Parties.</font></div>
            </td>
          </tr>

      </table>
      <div> <br>
      </div>
      <div id="DSPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
        <div id="DSPFPageNumberArea" style="text-align: center;"><font id="DSPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">50</font></div>
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          <hr style="border-width: 0px; clear: both; margin: 4px 0px; width: 100%; height: 2px; color: #000000; background-color: #000000;" noshade="noshade"></div>
        <div style="width: 100%;" id="DSPFPageHeader">Confidential</div>
      </div>
      <table id="z7ae04aa939e44f41ba3deec6511cf38e" class="DSPFListTable" style="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;"><a name="z_Ref302642829"></a><a name="z_Ref243202179"></a><font style="font-weight: bold;">11.4</font></td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Press Release; Publications; Disclosure of Agreement</u></font><font style="font-size: 10pt;">.</font></div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table id="za621de638f1d46d79b2e87293f70ef51" class="DSPFListTable" style="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: 36pt; vertical-align: top; font-weight: bold;">11.4.1</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Announcement of Transaction</u></font><font style="font-size: 10pt;">.&#160; On or promptly after the Effective Date, the Parties will issue a public announcement
                  of the execution of this Agreement in form and substance mutually agreed by the Parties and included in Schedule 11.4.</font></div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table id="z7ffed3fa3d894d04ad306e43dbc42a3d" class="DSPFListTable" style="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: 36pt; vertical-align: top; font-weight: bold;">11.4.2</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Other Disclosures</u></font><font style="font-size: 10pt;">.&#160; Except to the extent required to comply with applicable law, regulation, rule or legal process or
                  as otherwise permitted in accordance with this <u>Section 11.4</u>, neither Party nor such Party&#8217;s Affiliates will make any public announcements, press releases or other public disclosures concerning a Drug Discovery Program, a Product,
                  this Agreement or the terms or the subject matter hereof without the prior written consent of the other, which will not be unreasonably withheld, conditioned or delayed.</font></div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table id="z84f1c668f5174f3da9e9da88f582fc34" class="DSPFListTable" style="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: 36pt; vertical-align: top; font-weight: bold;">11.4.3</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Use of Name</u></font><font style="font-size: 10pt;">.&#160; Except as set forth in <u>Section 11.4.8</u>, neither Party will use the other Party&#8217;s name in a press
                  release or other publication without first obtaining the prior consent of the Party to be named.</font></div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table id="z60b7c08f932d4815a0c11f7d6b50c28f" class="DSPFListTable" style="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: 36pt; vertical-align: top; font-weight: bold;">11.4.4</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Notice of Significant Events</u></font><font style="font-size: 10pt;">.&#160; Each party will immediately notify (and provide as much advance notice as possible,
                  but at a minimum two Business Days advance notice to) the other Party of any event materially related to a Product (including in such notice any disclosure of starting/stopping of a Clinical Study, clinical data or results, material
                  regulatory discussions, filings, Approval or JBI&#8217;s sales projections) so the Parties may analyze the need for or desirability of publicly disclosing or reporting such event.</font></div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table id="z050229f222bf4faf9e108359d56db1a6" class="DSPFListTable" style="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: 36pt; vertical-align: top; font-weight: bold;">11.4.5</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>JBI Disclosures After Option Exercise</u></font><font style="font-size: 10pt;">.&#160; After Option if JBI intends to make a press release or similar public
                  communication disclosing regulatory discussions, the efficacy or safety data <font style="color: #000000;">or</font> results related to such Product or JBI&#8217;s sales projections, (i) JBI will submit such proposed communication to Isis for
                  review at least two Business Days in advance of such proposed public disclosure, (ii) Isis will have the right to review and recommend changes to such communication, and (iii) JBI will in good faith consider any changes that are timely
                  recommended by Isis.</font></div>
            </td>
          </tr>

      </table>
      <div> <br>
      </div>
      <div id="DSPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
        <div id="DSPFPageNumberArea" style="text-align: center;"><font id="DSPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">51</font></div>
        <div id="DSPFPageBreak" style="page-break-after: always;">
          <hr style="border-width: 0px; clear: both; margin: 4px 0px; width: 100%; height: 2px; color: #000000; background-color: #000000;" noshade="noshade"></div>
        <div style="width: 100%;" id="DSPFPageHeader">Confidential</div>
      </div>
      <table id="z5913374c39424656b149e85dc0361ccc" class="DSPFListTable" style="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: 36pt; vertical-align: top; font-weight: bold;">11.4.6</td>
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              <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Scientific or Clinical Presentations</u></font><font style="font-size: 10pt;">.&#160; The Parties agree to use Commercially Reasonable Efforts to control public
                  scientific disclosures of results of the Development activities under this Agreement to prevent any potential adverse effect of any premature public disclosure of such results.&#160; The Parties will establish a procedure for publication
                  review and each Party will first submit to the other Party through the Joint Patent Committee an early draft of all such publications or presentations, whether they are to be presented orally or in written form, at least 45 days prior to
                  submission for publication including to facilitate the publication of any summaries of Clinical Studies data and results as required on the clinical trial registry of each respective Party.&#160; Each Party will review such proposed
                  publication in order to avoid the unauthorized disclosure of a Party&#8217;s Confidential Information and to preserve the patentability of inventions arising from the Drug Discovery Programs.&#160; If, during such 45-day period, the other Party
                  informs such Party that its proposed publication contains Confidential Information of the other Party, then such Party will delete such Confidential Information from its proposed publication.&#160; In addition, if at any time during such
                  45-day period, the other Party informs such Party that its proposed publication discloses inventions made by either Party in the course of the Development under this Agreement that have not yet been protected through the filing of a
                  patent application, or the public disclosure of such proposed publication could be expected to have a material adverse effect on any Patent Rights or Know-How solely owned or Controlled by such other Party, then such Party will either (i)
                  delay such proposed publication for up to 60 days from the date the other Party informed such Party of its objection to the proposed publication, to permit the timely preparation and first filing of patent application(s) on the
                  information involved or (ii) remove the identified disclosures prior to publication.</font></div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table id="z4fae0c9c125b41cea4737155c2ab34dd" class="DSPFListTable" style="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: 36pt; vertical-align: top; font-weight: bold;">11.4.7</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Subsequent Disclosure</u></font><font style="font-size: 10pt;">.&#160; Notwithstanding the foregoing, to the extent information regarding this Agreement or the
                  Product has already been publicly disclosed, either Party (or its Affiliates) may subsequently disclose the same information to the public without the consent of the other Party.</font></div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table id="zbe0d1fe5234a4f1e8735a4e988670343" class="DSPFListTable" style="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: 36pt; vertical-align: top;"><a name="z_Ref309467424"></a><font style="font-weight: bold;">11.4.8</font></td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Acknowledgment</u></font><font style="font-size: 10pt;">.&#160; JBI will acknowledge in any press release, public presentation or publication regarding the
                  collaboration or a Product, Isis&#8217; role in discovering and developing the Product, that the Product is under license from Isis and otherwise acknowledge Isis&#8217; contributions, and Isis&#8217; stock ticker symbol (Nasdaq: ISIS).&#160; Isis may include
                  the Product (and identify JBI as its partner for the Product) in Isis&#8217; drug pipeline.</font></div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <div style="text-align: center; font-weight: bold;"><a name="z_Ref186448804"></a><a name="z_Ref243445322"></a>ARTICLE 12.</div>
      <div style="text-align: center; font-weight: bold;">MISCELLANEOUS</div>
      <div>&#160;</div>
      <table id="z1ef6289dbab84a939b5232f880a40347" class="DSPFListTable" style="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;"><a name="z_Ref189037800"></a><a name="z_Ref309571273"></a><a name="z_Ref186447395"></a><a name="z_Ref186448579"></a><font style="font-weight: bold;">12.1</font></td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Dispute Resolution</u></font><font style="font-size: 10pt;">.<a name="z_Ref243282683"></a><a name="z_Ref150948475"></a></font></div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table id="z380d703d641a422099b89cad9ecaede9" class="DSPFListTable" style="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: 36pt; vertical-align: top;"><a name="z_Ref404190985"></a><a name="z_Ref311531091"></a><font style="font-weight: bold;">12.1.1</font></td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>General</u></font><font style="font-weight: bold; font-size: 10pt;">.</font><font style="font-size: 10pt;">&#160; The Parties recognize that a dispute may arise
                  relating to this Agreement (&#8220;<font style="font-weight: bold; font-style: italic;">Dispute</font>&#8221;).&#160; Except as set forth in <u>Section 12.1.5</u> any Dispute, including Disputes that may involve the parent company, subsidiaries, or
                  affiliates under common control of any Party, shall be resolved in accordance with this Section 12.</font></div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table id="zbd8959108b084292a5f61739601ce30c" class="DSPFListTable" style="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: 36pt; vertical-align: top; font-weight: bold;">12.1.2</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Continuance of Rights and Obligations During Pendency of Dispute Resolution.</u></font><font style="font-size: 10pt;">&#160; If there are any Disputes in connection
                  with this Agreement, including Disputes related to termination of this Agreement under <u>Section 10</u>, all rights and obligations of the Parties shall continue until such time as any Dispute has been resolved in accordance with the
                  provisions of this <u>Section 12</u>.</font></div>
            </td>
          </tr>

      </table>
      <div> <br>
      </div>
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        <div id="DSPFPageNumberArea" style="text-align: center;"><font id="DSPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">52</font></div>
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      </div>
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          <tr>
            <td style="width: 36pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top; font-weight: bold;">12.1.3</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Escalation</u></font><font style="font-size: 10pt;">.&#160; Subject to Section 12.1.5, any claim, Dispute, or controversy as to the breach, enforcement,
                  interpretation or validity of this Agreement will be referred to the Global Therapeutic Area Head, Immunology of JBI and the Chief Operating Officer of Isis (the &#8220;<font style="font-weight: bold; font-style: italic;">Executives</font>&#8221;)
                  for attempted resolution.&#160; In the event the Executives are unable to resolve such Dispute within 30 days of such Dispute being referred to them, then, upon the written request of either Party to the other Party, the Dispute shall be
                  subject to arbitration in accordance with <u>Section 12.1.4</u>, except as expressly set forth in <u>Section 12.1.5</u> or <u>Section 12.3</u>.</font></div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table id="z0bf3cd04b960416ba3fc0b4c68a10263" 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;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;"><a name="z_Ref404063330"></a><a name="z_Ref311063878"></a><a name="z_Ref311115182"></a><font style="font-weight: bold;">12.1.4</font></td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Arbitration</u></font><font style="font-size: 10pt;">.</font></div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table id="z7fe0955626474d8aa3de0aa70c7ace40" 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: 72pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;"><a name="z_Toc141340339"></a><font style="font-weight: bold;">(a)</font></td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>If the Parties fail to resolve the Dispute through Escalation, and a Party desires to pursue resolution of the Dispute, the Dispute shall be submitted by either Party for resolution in arbitration pursuant to the then current CPR
                Non-Administered Arbitration Rules (&#8220;CPR Rules&#8221;) (www.cpradr.org), except where they conflict with these provisions, in which case these provisions control.&#160; The arbitration will be held in Chicago, Illinois. All aspects of the arbitration
                shall be treated as confidential.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table id="zfef45a562eb34993880fc22b56e6019a" 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: 72pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top; font-weight: bold;">(b)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>The arbitrators will be chosen from the CPR Panel of Distinguished Neutrals, unless a candidate not on such panel is approved by both Parties.&#160; Each arbitrator shall be a lawyer with at least 15 years of experience with a law firm or
                corporate law department of over 25 lawyers or who was a judge of a court of general jurisdiction.&#160; To the extent that the Dispute requires special expertise, the Parties will so inform CPR prior to the beginning of the selection process.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table id="ze1ac0f1902d7462a87f67922c414e4f1" 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: 72pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top; font-weight: bold;">(c)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>The arbitration tribunal shall consist of three arbitrators, of whom each Party shall designate one in accordance with the &#8220;screened&#8221; appointment procedure provided in CPR Rule 5.4.&#160; The chair will be chosen in accordance with CPR Rule
                6.4.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table id="za3028118169a49039216b840943b3545" 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: 72pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top; font-weight: bold;">(d)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>If, however, the aggregate award sought by the Parties is less than $5 million and equitable relief is not sought, a single arbitrator shall be chosen in accordance with the CPR Rules.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table id="zdfc96f7e9bb6464f9d6b3b2ef5f9ac59" 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: 72pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top; font-weight: bold;">(e)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>Candidates for the arbitrator position(s) may be interviewed by representatives of the Parties in advance of their selection, provided that all Parties are represented.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table id="zc50f702a6949468d8cee4ee643e9aad6" 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: 72pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top; font-weight: bold;">(f)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>The Parties agree to select the arbitrator(s) within 45 days of initiation of the arbitration.&#160; The hearing will be concluded within nine (9) months after selection of the arbitrator(s) and the award will be rendered within 60 days of
                the conclusion of the hearing, or of any post hearing briefing, which briefing will be completed by both sides within 45 days after the conclusion of the hearing.&#160; In the event the Parties cannot agree upon a schedule, then the
                arbitrator(s) shall set the schedule following the time limits set forth above as closely as practical.</div>
            </td>
          </tr>

      </table>
      <div> <br>
      </div>
      <div id="DSPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
        <div id="DSPFPageNumberArea" style="text-align: center;"><font id="DSPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">53</font></div>
        <div id="DSPFPageBreak" style="page-break-after: always;">
          <hr style="border-width: 0px; clear: both; margin: 4px 0px; width: 100%; height: 2px; color: #000000; background-color: #000000;" noshade="noshade"></div>
        <div style="width: 100%;" id="DSPFPageHeader">Confidential</div>
      </div>
      <table id="z7587840347ec479889498fef66b56ec3" 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>
            <td style="width: 36pt; vertical-align: top; font-weight: bold;">(g)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>The hearing will be concluded in ten hearing days or less.&#160; Multiple hearing days will be scheduled consecutively to the greatest extent possible.&#160; A transcript of the testimony adduced at the hearing shall be made and shall be made
                available to each Party.</div>
            </td>
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      </table>
      <div>&#160;</div>
      <table id="z6defd3e1bcd84d51a6e879bbb7477ae1" 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>
            <td style="width: 36pt; vertical-align: top; font-weight: bold;">(h)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>The arbitrator(s) shall be guided, but not bound, by the CPR Protocol on Disclosure of Documents and Presentation of Witnesses in Commercial Arbitration (www.cpradr.org) (&#8220;Protocol&#8221;).&#160; The Parties will attempt to agree on modes of
                document disclosure, electronic discovery, witness presentation, etc. within the parameters of the Protocol.&#160; If the Parties cannot agree on discovery and presentation issues, the arbitrator(s) shall decide on presentation modes and provide
                for discovery within the Protocol, understanding that the Parties contemplate reasonable discovery.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table id="z4c5d0375a57c4a48b503655d9fa2e415" 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>
            <td style="width: 36pt; vertical-align: top; font-weight: bold;">(i)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>The arbitrator(s) shall decide the merits of any Dispute in accordance with the law governing this Agreement, without application of any principle of conflict of laws that would result in reference to a different law.&#160; The arbitrator(s)
                may not apply principles such as &#8220;amiable compositeur&#8221; or &#8220;natural justice and equity.&#8221;</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table id="z45e0f4c7d3b8468eaeb713ce31212852" 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: 72pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top; font-weight: bold;">(j)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>The arbitrator(s) are expressly empowered to decide dispositive motions in advance of any hearing and shall endeavor to decide such motions as would a United States District Court Judge sitting in the jurisdiction whose substantive law
                governs.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table id="z45d1e9666d844627a5fd9bb27fe34734" 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: 72pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top; font-weight: bold;">(k)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>The arbitrator(s) shall render a written opinion stating the reasons upon which the award is based.&#160; The Parties consent to the jurisdiction of the United States District Court for the district in which the arbitration is held for the
                enforcement of these provisions and the entry of judgment on any award rendered hereunder.&#160; Should such court for any reason lack jurisdiction, any court with jurisdiction may act in the same fashion.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table id="zac83ed81276747d18df6ebee53cc0ca3" 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: 72pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top; font-weight: bold;">(l)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>Each Party has the right to seek from the appropriate court provisional remedies such as attachment, preliminary injunction, replevin, etc. to avoid irreparable harm, maintain the status quo, or preserve the subject matter of the
                Dispute.&#160; Rule 14 of the CPR Rules does not apply to this Agreement.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table id="zb98e5f72e2994a58af12e2f2a68c4a04" 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: 72pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top; font-weight: bold;">(m)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>EXCEPT IN THE CASE OF COURT ACTIONS PERMITTED BY <u>SECTION 12.1.5</u> AND FOR CLAIMS NOT SUBJECT TO ARBITRATION PURSUANT TO <u>SECTION</u>&#160;<u>12.1.4 AS SET FORTH IN SECTION 12.1.5</u>, EACH PARTY HERETO WAIVES: (1) ITS RIGHT TO TRIAL
                OF ANY ISSUE BY JURY, (2) WITH THE EXCEPTION OF RELIEF MANDATED BY STATUTE, ANY CLAIM TO PUNITIVE, EXEMPLARY, MULTIPLIED, INDIRECT, CONSEQUENTIAL OR LOST PROFITS/REVENUES DAMAGES, AND (3) ANY CLAIM FOR ATTORNEY FEES, COSTS AND PREJUDGMENT
                INTEREST.</div>
            </td>
          </tr>

      </table>
      <div> <br>
      </div>
      <div id="DSPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
        <div id="DSPFPageNumberArea" style="text-align: center;"><font id="DSPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">54</font></div>
        <div id="DSPFPageBreak" style="page-break-after: always;">
          <hr style="border-width: 0px; clear: both; margin: 4px 0px; width: 100%; height: 2px; color: #000000; background-color: #000000;" noshade="noshade"></div>
        <div style="width: 100%;" id="DSPFPageHeader">Confidential</div>
      </div>
      <table id="zc7958dcedc0a41c494c15a0e24867e40" 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: 72pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;"><a name="z_Toc320284687"></a><font style="font-weight: bold;">(n)</font></td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>Each Party will bear its own attorney&#8217;s fees, costs, and disbursements arising out of the arbitration, and will pay an equal share of the fees and costs of the arbitrator; <font style="font-style: italic;">provided, however,</font> the
                arbitrator will be authorized to determine whether a Party is the prevailing party, and if so, to award to that prevailing party reimbursement for any or all of its reasonable attorneys&#8217; fees, costs and disbursements (including, for
                example, expert witness fees and expenses, photocopy charges, travel expenses, <font style="font-style: italic;">etc.</font>), and/or the fees and costs of the Administrator and the arbitrator.</div>
            </td>
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      </table>
      <div>&#160;</div>
      <table id="z89dca9cc86174d20b4c035d983e76f9a" class="DSPFListTable" style="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: 36pt; vertical-align: top;"><a name="z_Ref336617182"></a><a name="z_Toc141340343"></a><a name="z_Ref406165554"></a><a name="z_Ref404062664"></a><font style="font-weight: bold;">12.1.5</font></td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Injunctive Relief; Court Actions</u></font><font style="font-weight: bold; font-size: 10pt;">.</font><font style="font-size: 10pt;">&#160; Notwithstanding anything
                  to the contrary in this Agreement, each Party will be entitled to seek from any court of competent jurisdiction, in addition to any other remedy it may have at law or in equity, injunctive or other equitable relief in the event of an
                  actual or threatened breach of this Agreement by the other Party, without the posting of any bond or other security, and such an action may be filed and maintained notwithstanding any ongoing discussions between the Parties or any ongoing
                  arbitration proceeding.&#160; The Parties agree that in the event of a threatened or actual material breach of this Agreement injunctive or equitable relief would be appropriate remedy.&#160; In addition, either Party may bring an action in any
                  court of competent jurisdiction to resolve disputes pertaining to the validity, construction, scope, enforceability, infringement or other violations of Patent Rights or other intellectual property rights, and no such claim will be
                  subject to arbitration pursuant to <u>Section 12.1.4</u>.</font></div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table id="z20acf78729c04d4a8e7c26e5f5701c2f" class="DSPFListTable" style="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;"><a name="z_Ref311065459"></a><font style="font-weight: bold;">12.2</font></td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Governing Law; Jurisdiction; Venue; Service of Process</u></font><font style="font-size: 10pt;">.&#160; This Agreement and any Dispute will be governed by and
                  construed and enforced in accordance with the laws of the State of New York, U.S.A., without reference to conflicts of laws principles.</font></div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table id="zba36e14aa7ed4da4b2ca85e73b5a54fa" class="DSPFListTable" style="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;"><a name="z_Ref404062668"></a><a name="z_Ref304119354"></a><font style="font-weight: bold;">12.3</font></td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Recovery of Losses</u></font><font style="font-size: 10pt;">.&#160; Neither Party will be entitled to recover any Losses relating to any matter arising under one
                  provision of this Agreement to the extent that such Party has already recovered Losses with respect to such matter pursuant to other provisions of this Agreement (including recoveries under <u>Section 9.1</u> or <u>Section 9.2</u>, and
                  the offsets under <u>Section 6.9.3(c)</u>).&#160; Except for the offsets and credits explicitly set forth in <u>Section 6.12</u>, and <u>Section 6.9.3(b)</u> neither Party will have the right to set off any amount it is owed or believes it
                  is owed against payments due or payable to the other Party under this Agreement.</font></div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table id="z979f2c3561754171b106b3537447bb87" class="DSPFListTable" style="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;"><a name="z_Ref311533129"></a><a name="z_Ref406165364"></a><a name="z_Ref311733861"></a><a name="z_Ref312153620"></a><font style="font-weight: bold;">12.4</font></td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Assignment and Successors</u></font><font style="font-size: 10pt;">.&#160; Neither this Agreement nor any obligation of a Party hereunder may be assigned by either
                  Party without the prior written consent of the other, which will not be unreasonably withheld, delayed or conditioned, except that (i) Isis may assign or transfer its rights to receive payments under this Agreement (but no liabilities),
                  without JBI&#8217;s consent, to an Affiliate or to a Third Party in connection with a payment factoring transaction, and (ii) each Party may assign this Agreement and the rights, obligations and interests of such Party hereunder, without the
                  other Party&#8217;s consent to any Third Party purchaser of all or substantially all of its assets or all or substantially all of its assets to which this Agreement relates or to any successor corporation resulting from any merger,
                  consolidation, share exchange or other similar transaction with a Third Party, provided that in the event of any such transaction (whether this Agreement is actually assigned or is assumed by the acquiring Third Party or the successor
                  corporation (as applicable) by operation of law (<font style="font-style: italic;">e.g.</font>, in the context of a reverse triangular merger)), intellectual property rights of the acquiring Third Party that existed prior to such
                  transaction shall not be included in the technology licensed hereunder or otherwise subject to this Agreement; <u>provided</u> that if JBI transfers or assigns this Agreement to [***] described in this Agreement, then JBI (or such
                  Affiliate), will [***] due Isis under <u>ARTICLE 6</u> for the [***] (defined below) such that Isis receives [***].</font></div>
            </td>
          </tr>

      </table>
      <div> <br>
      </div>
      <div id="DSPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
        <div id="DSPFPageNumberArea" style="text-align: center;"><font id="DSPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">55</font></div>
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      </div>
      <div style="text-align: justify; margin-left: 36pt;">The [***].</div>
      <div>&#160;</div>
      <div style="text-align: justify; margin-left: 36pt;">To the extent Isis utilizes [***] in any year, Isis will [***] to JBI [***].&#160; To assist JBI in determining when [***] pursuant to the foregoing sentence, beginning with the first Annual tax return
        for the year in which JBI [***] payment under this <u>Section 12.4</u>, and each year thereafter (including, for clarity, all years in which Isis [***], Isis will provide JBI with Isis&#8217; Annual tax returns (federal and state) and, in years in which
        Isis utilizes [***], supporting documentation for such [***].&#160; Notwithstanding the foregoing, if the [***].</div>
      <div>&#160;</div>
      <div style="text-align: justify; margin-left: 36pt;"><font style="font-weight: bold;">12.4.1</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<font style="font-weight: bold;"><u>Termination of Reporting Obligations Upon Isis Change of Control</u></font>.&#160; If there is a change in
        control of Isis, JBI, at its discretion, may terminate all reporting obligations regarding the Development and/or Commercialization of any Products including reporting under the Information Sharing Committee, except in all cases JBI will continue
        to provide the reports, audit rights and other information required under <u>Sections 6.10</u>, <u>6.11</u>, <u>6.12</u> and <u>6.13</u>.</div>
      <div>&#160;</div>
      <table id="ze2486292ba614d029b72e12c1805f9ec" class="DSPFListTable" style="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;">12.5</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Force Majeure</u></font><font style="font-size: 10pt;">.&#160; No Party will be held 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 performing any obligation of this Agreement when such failure or delay is due to force majeure, and without the fault or negligence of the Party so failing or delaying.&#160;
                  For purposes of this Agreement, force majeure means a cause beyond the reasonable control of a Party, which may include acts of God; acts, regulations, or laws of any government; war; terrorism; civil commotion; fire, flood, earthquake,
                  tornado, tsunami, explosion or storm; pandemic; epidemic and failure of public utilities or common carriers.&#160; In such event the Party so failing or delaying will immediately notify the other Party of such inability and of the period for
                  which such inability is expected to continue.&#160; The Party giving such notice will be excused from such of its obligations under this Agreement as it is thereby disabled from performing for so long as it is so disabled for up to a maximum
                  of 90 days, after which time the Parties will negotiate in good faith any modifications of the terms of this Agreement that may be necessary to arrive at an equitable solution, unless the Party giving such notice has set out a reasonable
                  timeframe and plan to resolve the effects of such force majeure and executes such plan within such timeframe.&#160; To the extent possible, each Party will use reasonable efforts to minimize the duration of any force majeure.</font></div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
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          <tr>
            <td style="width: 36pt; vertical-align: top;"><a name="z_Ref311064869"></a><font style="font-weight: bold;">12.6</font></td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Notices</u></font><font style="font-size: 10pt;">.&#160; Any notice or request required or permitted to be given under or in connection with this Agreement will be
                  deemed to have been sufficiently given if in writing and personally delivered or sent by certified mail (return receipt requested), facsimile transmission (receipt verified), or overnight express courier service (signature required),
                  prepaid, to the Party for which such notice is intended, at the address set forth for such Party below:</font></div>
            </td>
          </tr>

      </table>
      <div> <br>
      </div>
      <div id="DSPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
        <div id="DSPFPageNumberArea" style="text-align: center;"><font id="DSPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">56</font></div>
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          <tr>
            <td style="width: 36pt;"><br>
            </td>
            <td style="width: 180pt; vertical-align: top;">If to Isis, addressed to:</td>
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              <div>Isis Pharmaceuticals, Inc.</div>
            </td>
          </tr>

      </table>
      <div style="margin-left: 216pt;">2855 Gazelle Court</div>
      <div style="margin-left: 216pt;">Carlsbad, CA&#160; 92010</div>
      <div style="margin-left: 216pt;">Attention:&#160; Chief Operating Officer</div>
      <div style="margin-left: 216pt;">Fax:&#160; 760-918-3592</div>
      <div>&#160;</div>
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          <tr>
            <td style="width: 36pt;"><br>
            </td>
            <td style="width: 180pt; vertical-align: top;">with a copy to:</td>
            <td style="width: auto; vertical-align: top;">
              <div>Isis Pharmaceuticals, Inc.</div>
            </td>
          </tr>

      </table>
      <div style="margin-left: 216pt;">2855 Gazelle Court</div>
      <div style="margin-left: 216pt;">Carlsbad, CA&#160; 92010</div>
      <div style="margin-left: 216pt;">Attention:&#160; General Counsel</div>
      <div style="margin-left: 216pt;">Fax:&#160; 760-268-4922</div>
      <div>&#160;</div>
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          <tr>
            <td style="width: 36pt;"><br>
            </td>
            <td style="width: 180pt; vertical-align: top;">If to JBI, addressed to:</td>
            <td style="width: auto; vertical-align: top;">
              <div>Janssen Research &amp; Development, LLC</div>
            </td>
          </tr>

      </table>
      <div style="margin-left: 216pt;">Murray McKinnon, PhD1400 McKean Road</div>
      <div style="margin-left: 216pt;">Spring House, PA&#160; 19477</div>
      <div style="text-indent: 0pt; margin-left: 216pt;">Mmckinno2@its.jnj.com</div>
      <div>with a copy to:</div>
      <div style="margin-left: 216pt; color: rgb(0, 0, 0);">Chief Patent Counsel</div>
      <div style="margin-left: 216pt; color: rgb(0, 0, 0);">Johnson &amp; Johnson</div>
      <div style="margin-left: 216pt;">One Johnson &amp; Johnson Plaza</div>
      <div style="margin-left: 216pt; color: rgb(0, 0, 0);">New Brunswick, NJ&#160; 08933</div>
      <div style="margin-left: 216pt; color: rgb(0, 0, 0);">Attn: Brian Carey</div>
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          <tr>
            <td style="width: 36pt;"><br>
            </td>
            <td style="width: 180pt; vertical-align: top; align: right;"><br>
            </td>
            <td style="width: auto; vertical-align: top;">
              <div><u>Bcarey2@its.jnj.com</u></div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <div style="text-align: justify; margin-left: 36pt;">or to such other address for such Party as it will have specified by like notice to the other Party; <font style="font-style: italic;">provided that</font> notices of a change of address will be
        effective only upon receipt thereof.&#160; If delivered personally or by facsimile transmission, the date of delivery will be deemed to be the date on which such notice or request was given.&#160; If sent by overnight express courier service, the date of
        delivery will be deemed to be the next Business Day after such notice or request was deposited with such service.&#160; If sent by certified mail, the date of delivery will be deemed to be the third Business Day after such notice or request was
        deposited with the U.S. Postal Service.</div>
      <div>&#160;</div>
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          <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 style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>ISIS Reporting of This Agreement</u></font><font style="font-size: 10pt;">.&#160; Isis shall provide JBI with at least [***] ([***]) days written notice of any
                  disclosure of this document to a Third Party or to a governmental authority.&#160; The Parties agree to promptly convene to discuss such disclosure and discuss, <font style="font-style: italic;">inter alia,</font> the subject matter that may
                  be redacted prior to such submission.&#160; Notwithstanding the foregoing, Isis may (i) disclose this Agreement to Isis&#8217; legal counsel, auditors, and other professional advisors on a need-to-know basis, in each case where such advisors have
                  agreed to confidentiality provisions no less restrictive than those of this Agreement, and (ii) may disclose the publicly available redacted version of this Agreement once such redacted version has been filed publicly with the SEC.</font></div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
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          <tr>
            <td style="width: 36pt; vertical-align: top; font-weight: bold;">12.8</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Export Clause</u></font><font style="font-size: 10pt;">.&#160; Each Party acknowledges that the laws and regulations of the United States restrict the export and
                  re-export of commodities and technical data of United States origin.&#160; Each Party agrees that it will not export or re-export restricted commodities or the technical data of the other Party in any form without the appropriate United States
                  and foreign government licenses.</font></div>
            </td>
          </tr>

      </table>
      <div> <br>
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        <div id="DSPFPageNumberArea" style="text-align: center;"><font id="DSPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">57</font></div>
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            <td style="width: 36pt; vertical-align: top; font-weight: bold;">12.9</td>
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              <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Waiver</u></font><font style="font-size: 10pt;">.&#160; Neither Party may waive or release any of its rights or interests in this Agreement except in writing.&#160; The
                  failure of either Party to assert a right hereunder or to insist upon compliance with any term or condition of this Agreement will not constitute a waiver of that right or excuse a similar subsequent failure to perform any such term or
                  condition.&#160; No waiver by either Party of any condition or term in any one or more instances will be construed as a continuing waiver or subsequent waiver of such condition or term or of another condition or term.</font></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;">12.10</td>
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              <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Severability</u></font><font style="font-size: 10pt;">.&#160; If any provision hereof should be held invalid, illegal or unenforceable in any jurisdiction, the
                  Parties will negotiate in good faith a valid, legal and enforceable substitute provision that most nearly reflects the original intent of the Parties and all other provisions hereof will remain in full force and effect in such
                  jurisdiction and will be liberally construed in order to carry out the intentions of the Parties hereto as nearly as may be possible.&#160; Such invalidity, illegality or unenforceability will not affect the validity, legality or
                  enforceability of such provision in any other jurisdiction.</font></div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
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          <tr>
            <td style="width: 36pt; vertical-align: top; font-weight: bold;">12.11</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Entire Agreement</u></font><font style="font-size: 10pt;">.&#160; This Agreement, together with the Schedules and Appendices hereto, sets forth all the covenants,
                  promises, agreements, warranties, representations, conditions and understandings between the Parties and supersedes and terminates all prior agreements and understanding between the Parties.&#160; There are no covenants, promises, agreements,
                  warranties, representations, conditions or understandings, either oral or written, between the Parties other than as set forth herein and therein.&#160; No subsequent alteration, amendment, change or addition to this Agreement will be binding
                  upon the Parties hereto unless reduced to writing and signed by the respective authorized officers of the Parties.</font></div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
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          <tr>
            <td style="width: 36pt; vertical-align: top; font-weight: bold;">12.12</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Independent Contractors</u></font><font style="font-size: 10pt;">.&#160; Nothing herein will be construed to create any relationship of employer and employee, agent
                  and principal, partnership or joint venture between the Parties.&#160; Each Party is an independent contractor.&#160; Neither Party will assume, either directly or indirectly, any liability of or for the other Party.&#160; Neither Party will have the
                  authority to bind or obligate the other Party, and neither Party will represent that it has such authority.</font></div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
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          <tr>
            <td style="width: 36pt; vertical-align: top; font-weight: bold;">12.13</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Interpretation</u></font><font style="font-size: 10pt;">.&#160; Except as otherwise explicitly specified to the contrary, (a) references to a section, exhibit or
                  schedule means a section of, or schedule or exhibit to this Agreement, unless another agreement is specified, (b) the word &#8220;including&#8221; (in its various forms) means &#8220;including without limitation,&#8221; (c) the words &#8220;shall&#8221; and &#8220;will&#8221; have the
                  same meaning, (d) references to a particular statute or regulation include all rules and regulations thereunder and any predecessor or successor statute, rules or regulation, in each case as amended or otherwise modified from time to
                  time, (e) words in the singular or plural form include the plural and singular form, respectively, (f) references to a particular Person include such Person&#8217;s successors and assigns to the extent not prohibited by this Agreement, (g)
                  unless otherwise specified, &#8220;$&#8221; is in reference to United States dollars, and (h) the headings contained in this Agreement, in any exhibit or schedule to this Agreement and in the table of contents to this Agreement are for convenience
                  only and will not in any way affect the construction of or be taken into consideration in interpreting this Agreement.</font></div>
            </td>
          </tr>

      </table>
      <div> <br>
      </div>
      <div id="DSPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
        <div id="DSPFPageNumberArea" style="text-align: center;"><font id="DSPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">58</font></div>
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      <table id="z98ddc96f2a3c4e8892ad9a2eeb52966c" 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;">12.14</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Books and Records</u></font><font style="font-size: 10pt;">.&#160; Any books and records to be maintained under this Agreement by a Party or its Affiliates or
                  Sublicensees will be maintained in accordance with U.S. Generally Accepted Accounting Principles (or any successor standard), consistently applied.</font></div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
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          <tr>
            <td style="width: 36pt; vertical-align: top; font-weight: bold;">12.15</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Further Actions</u></font><font style="font-size: 10pt;">.&#160; Each Party will execute, acknowledge and deliver such further instruments, and do all such other
                  acts, as may be necessary or appropriate in order to carry out the expressly stated purposes and the clear intent of this Agreement.</font></div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table id="z29d66d1a2f514b59a10f6632eeb24fab" 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;">12.16</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Construction of Agreement</u></font><font style="font-size: 10pt;">.&#160; The terms and provisions of this Agreement represent the results of negotiations between
                  the Parties and their representatives, each of which has been represented by counsel of its own choosing, and neither of which has acted under duress or compulsion, whether legal, economic or otherwise.&#160; Accordingly, the terms and
                  provisions of this Agreement will be interpreted and construed in accordance with their usual and customary meanings, and each of the Parties hereto hereby waives the application in connection with the interpretation and construction of
                  this Agreement of any rule of law to the effect that ambiguous or conflicting terms or provisions contained in this Agreement will be interpreted or construed against the Party whose attorney prepared the executed draft or any earlier
                  draft of this Agreement.</font></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;">12.17</td>
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              <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Supremacy</u></font><font style="font-size: 10pt;">.&#160; In the event of any express conflict or inconsistency between this Agreement and any Schedule or Appendix
                  hereto, the terms of this Agreement will apply.&#160; The Parties understand and agree that the Schedules identifying the Licensed Technology are not intended to be the final and complete embodiment of any terms or provisions of this
                  Agreement, and are to be updated from time to time during the Agreement Term, as appropriate and in accordance with the provisions of this Agreement.</font></div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table id="z3684e6f10edf45e39b6f2fde03ab499b" class="DSPFListTable" style="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;">12.18</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Counterparts</u></font><font style="font-size: 10pt;">.&#160; This Agreement may be signed in counterparts, each of which will be deemed an original,
                  notwithstanding variations in format or file designation which may result from the electronic transmission, storage and printing of copies of this Agreement from separate computers or printers.&#160; Facsimile signatures and signatures
                  transmitted via electronic mail in PDF format will be treated as original signatures.</font></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;">12.19</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div style="font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;"><u>Compliance with Laws</u></font><font style="font-size: 10pt;">.&#160; Each Party will, and will ensure that its Affiliates and Sublicensees will, comply with all
                  relevant laws and regulations in exercising its rights and fulfilling its obligations under this Agreement.</font></div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <div style="text-align: center; font-style: italic;">[SIGNATURE PAGE FOLLOWS]</div>
      <div>&#160;</div>
      <div style="text-align: center;">* - * - * - *</div>
      <div>&#160;</div>
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        <div id="DSPFPageNumberArea" style="text-align: center;"><font id="DSPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">59</font></div>
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      <div style="text-align: justify; text-indent: 36pt; font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;">IN WITNESS WHEREOF</font><font style="font-size: 10pt;">, the Parties have caused this Agreement to be executed by their
          representatives thereunto duly authorized as of the Effective Date.</font></div>
      <div>&#160;</div>
      <div>
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            <tr>
              <td colspan="2">
                <div style="text-align: justify; font-weight: bold;">ISIS PHARMACEUTICALS, INC.</div>
              </td>
              <td style="width: 50%;">
                <div>&#160;</div>
              </td>
            </tr>
            <tr>
              <td colspan="2">
                <div>&#160;</div>
              </td>
              <td style="width: 50%;">
                <div>&#160;</div>
              </td>
            </tr>
            <tr>
              <td style="width: 3%;">
                <div style="text-align: justify;">By:</div>
              </td>
              <td style="width: 47%;"><u>/s/ B. Lynne Parshall</u></td>
              <td style="width: 50%;">
                <div>&#160;</div>
              </td>
            </tr>

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            <tr>
              <td rowspan="1" style="width: 5%;">
                <div style="text-align: justify;">Name:<br>
                </div>
              </td>
              <td rowspan="1" style="width: 45%;">B. Lynne Parshall</td>
              <td rowspan="1" style="width: 50%;">&#160;</td>
            </tr>
            <tr>
              <td rowspan="1" style="width: 5%;">
                <div>Title:<br>
                </div>
              </td>
              <td rowspan="1" style="width: 45%;">Chief Operating Officer</td>
              <td rowspan="1" style="width: 50%;">&#160;</td>
            </tr>

        </table>
      </div>
      <div> <br>
      </div>
      <div>
        <div style="text-align: center; font-variant: small-caps; font-weight: bold;">Signature Page to Research Collaboration, Option and License Agreement</div>
      </div>
      <div style="text-align: justify;"><br>
      </div>
      <div id="DSPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
        <div id="DSPFPageNumberArea" style="text-align: center;"><font id="DSPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">60</font></div>
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        <div style="width: 100%;" id="DSPFPageHeader">Confidential</div>
      </div>
      <div><br>
      </div>
      <div style="text-align: justify; text-indent: 36pt; font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;">IN WITNESS WHEREOF</font><font style="font-size: 10pt;">, the Parties have caused this Agreement to be executed by their
          representatives thereunto duly authorized as of the Effective Date.</font></div>
      <div>&#160;</div>
      <div>
        <div>
          <table id="z154949129c784ab6af0f0a4265547d9a" style="font-family: 'Times New Roman'; font-size: 10pt; color: #000000; width: 100%;" border="0" cellpadding="0" cellspacing="0">

              <tr>
                <td colspan="2">
                  <div style="text-align: justify; font-weight: bold;">JANSSEN BIOTECH INC.</div>
                </td>
                <td style="width: 50%;">
                  <div>&#160;</div>
                </td>
              </tr>
              <tr>
                <td colspan="2">
                  <div>&#160;</div>
                </td>
                <td style="width: 50%;">
                  <div>&#160;</div>
                </td>
              </tr>
              <tr>
                <td style="width: 3%;">
                  <div style="text-align: justify;">By:</div>
                </td>
                <td style="width: 47%;"><u>/s/ John Wilson</u></td>
                <td style="width: 50%;">
                  <div>&#160;</div>
                </td>
              </tr>

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

              <tr>
                <td rowspan="1" style="width: 5%;">&#160;</td>
                <td rowspan="1" style="width: 45%;">&#160;</td>
                <td rowspan="1" style="width: 50%;">&#160;</td>
              </tr>
              <tr>
                <td rowspan="1" style="width: 5%;">
                  <div style="text-align: justify;">Name:<br>
                  </div>
                </td>
                <td rowspan="1" style="width: 45%;">John Wilson</td>
                <td rowspan="1" style="width: 50%;">&#160;</td>
              </tr>
              <tr>
                <td rowspan="1" style="width: 5%;">&#160;</td>
                <td rowspan="1" style="width: 45%;">&#160;</td>
                <td rowspan="1" style="width: 50%;">&#160;</td>
              </tr>
              <tr>
                <td rowspan="1" style="width: 5%;">
                  <div>Title:<br>
                  </div>
                </td>
                <td rowspan="1" style="width: 45%;">Vice President, Janssen Biotech Inc</td>
                <td rowspan="1" style="width: 50%;">&#160;</td>
              </tr>

          </table>
        </div>
      </div>
      <div> <br>
      </div>
      <div>
        <div style="text-align: center; font-variant: small-caps; font-weight: bold;">Signature Page to Research Collaboration, Option and License Agreement</div>
      </div>
      <div>&#160;</div>
      <div id="DSPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
        <div id="DSPFPageNumberArea" style="text-align: center;"><font id="DSPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">61</font></div>
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        <div style="width: 100%;" id="DSPFPageHeader">Confidential</div>
      </div>
      <div style="text-align: center; font-weight: bold;"><u>List of Appendices and Schedules</u></div>
      <div>&#160;</div>
      <div>
        <table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: rgb(0, 0, 0);" id="z1927780429164bd5abfa2e6467cc38cf" border="0" cellpadding="0" cellspacing="0">

            <tr>
              <td style="width: 100%; vertical-align: top; background-color: rgb(204, 238, 255);">
                <div style="text-align: justify; font-size: 12pt; color: rgb(0, 0, 0);"><font style="font-size: 10pt; font-variant: small-caps;"><u>Appendix 1</u></font><font style="font-size: 10pt;"> &#8211; Definitions</font></div>
              </td>
            </tr>
            <tr>
              <td rowspan="1" style="width: 100%; vertical-align: top; color: rgb(0, 0, 0);">&#160;</td>
            </tr>
            <tr>
              <td style="width: 100%; vertical-align: top; background-color: rgb(204, 238, 255);">
                <div style="text-align: justify; font-size: 12pt; color: rgb(0, 0, 0);"><font style="font-size: 10pt; font-variant: small-caps;"><u>Appendix 2</u></font><font style="font-size: 10pt;"> &#8211; Development Candidate Checklist</font></div>
              </td>
            </tr>
            <tr>
              <td rowspan="1" style="width: 100%; vertical-align: top; color: rgb(0, 0, 0);">&#160;</td>
            </tr>
            <tr>
              <td style="width: 100%; vertical-align: top; background-color: rgb(204, 238, 255);">
                <div style="text-align: justify; font-size: 12pt; color: rgb(0, 0, 0);"><font style="font-size: 10pt; font-variant: small-caps;"><u>Appendix 3</u></font><font style="font-size: 10pt;"> &#8211; J&amp;J Universal Calendar</font></div>
              </td>
            </tr>
            <tr>
              <td rowspan="1" style="width: 100%; vertical-align: top; color: rgb(0, 0, 0);">&#160;</td>
            </tr>
            <tr>
              <td style="width: 100%; vertical-align: top; background-color: rgb(204, 238, 255);">
                <div style="text-align: justify; font-size: 12pt;"><font style="font-variant: small-caps; font-size: 10pt;"><u>Schedule 1.6.1</u></font><font style="font-variant: small-caps; font-size: 10pt;"> &#8211; </font><font style="font-size: 10pt;">JRC
                    Governance</font></div>
              </td>
            </tr>
            <tr>
              <td rowspan="1" style="width: 100%; vertical-align: top; color: rgb(0, 0, 0);">&#160;</td>
            </tr>
            <tr>
              <td style="width: 100%; vertical-align: top; background-color: rgb(204, 238, 255);">
                <div style="text-align: justify; font-size: 12pt;"><font style="font-variant: small-caps; font-size: 10pt;"><u>Schedule 1.6.5</u></font><font style="font-size: 10pt;"> &#8211; Alliance Management Activities</font></div>
              </td>
            </tr>
            <tr>
              <td rowspan="1" style="width: 100%; vertical-align: top; color: rgb(0, 0, 0);">&#160;</td>
            </tr>
            <tr>
              <td style="width: 100%; vertical-align: top; background-color: rgb(204, 238, 255);">
                <div style="text-align: justify; font-size: 12pt;"><font style="font-variant: small-caps; font-size: 10pt;"><u>Schedule 4.4.4</u></font><font style="font-size: 10pt;"> &#8211; Isis&#8217; Fully Absorbed Cost of Goods Methodology</font></div>
              </td>
            </tr>
            <tr>
              <td rowspan="1" style="width: 100%; vertical-align: top; color: rgb(0, 0, 0);">&#160;</td>
            </tr>
            <tr>
              <td style="width: 100%; vertical-align: top; background-color: rgb(204, 238, 255);">
                <div style="text-align: justify; font-size: 12pt;"><font style="font-variant: small-caps; font-size: 10pt;"><u>Schedule 5.2</u></font><font style="font-size: 10pt;"> &#8211; Specific Performance Milestone Events</font></div>
              </td>
            </tr>
            <tr>
              <td rowspan="1" style="width: 100%; vertical-align: top; color: rgb(0, 0, 0);">&#160;</td>
            </tr>
            <tr>
              <td style="width: 100%; vertical-align: top; background-color: rgb(204, 238, 255);">
                <div style="text-align: justify; font-size: 12pt;"><font style="font-variant: small-caps; font-size: 10pt;"><u>Schedule</u></font><font style="font-size: 10pt;"><u> 6.9.1</u> &#8211; Certain Isis In-License Agreements</font></div>
              </td>
            </tr>
            <tr>
              <td rowspan="1" style="width: 100%; vertical-align: top; color: rgb(0, 0, 0);">&#160;</td>
            </tr>
            <tr>
              <td style="width: 100%; vertical-align: top; background-color: rgb(204, 238, 255);">
                <div style="text-align: justify; font-size: 12pt;"><font style="font-variant: small-caps; font-size: 10pt;"><u>Schedule</u></font><font style="font-size: 10pt;"><u> 8.2.2(a)</u> &#8211; Isis Core Technology Patents</font></div>
              </td>
            </tr>
            <tr>
              <td rowspan="1" style="width: 100%; vertical-align: top; color: rgb(0, 0, 0);">&#160;</td>
            </tr>
            <tr>
              <td style="width: 100%; vertical-align: top; background-color: rgb(204, 238, 255);">
                <div style="text-align: justify; font-size: 12pt;"><font style="font-variant: small-caps; font-size: 10pt;"><u>Schedule</u></font><font style="font-size: 10pt;"><u> 8.2.2(b)</u> &#8211; Isis Manufacturing and Analytical Patents</font></div>
              </td>
            </tr>
            <tr>
              <td rowspan="1" style="width: 100%; vertical-align: top; color: rgb(0, 0, 0);">&#160;</td>
            </tr>
            <tr>
              <td style="width: 100%; vertical-align: top; background-color: rgb(204, 238, 255);">
                <div style="text-align: justify; font-size: 12pt;"><font style="font-variant: small-caps; font-size: 10pt;"><u>Schedule</u></font><font style="font-size: 10pt;"><u> 8.2.2(c)</u> &#8211; Isis Product-Specific Patents</font></div>
              </td>
            </tr>
            <tr>
              <td rowspan="1" style="width: 100%; vertical-align: top; color: rgb(0, 0, 0);">&#160;</td>
            </tr>
            <tr>
              <td style="width: 100%; vertical-align: top; background-color: rgb(204, 238, 255);">
                <div style="text-align: justify; font-size: 12pt;"><font style="font-variant: small-caps; font-size: 10pt;"><u>Schedule</u></font><font style="font-size: 10pt;"><u> 8.2.2(d)</u> &#8211; Isis Formulation Patents</font></div>
              </td>
            </tr>
            <tr>
              <td rowspan="1" style="width: 100%; vertical-align: top; color: rgb(0, 0, 0);">&#160;</td>
            </tr>
            <tr>
              <td style="width: 100%; vertical-align: top; background-color: rgb(204, 238, 255);">
                <div style="text-align: justify; font-size: 12pt;"><font style="font-variant: small-caps; font-size: 10pt;"><u>Schedule 11.4</u></font><font style="font-variant: small-caps; font-size: 10pt;"> &#8211; </font><font style="font-size: 10pt;">Press
                    Release</font></div>
              </td>
            </tr>
            <tr>
              <td rowspan="1" style="width: 100%; vertical-align: top; color: rgb(0, 0, 0);">&#160;</td>
            </tr>
            <tr>
              <td style="width: 100%; vertical-align: top; background-color: rgb(204, 238, 255);">
                <div style="text-align: justify; font-size: 12pt;"><font style="font-variant: small-caps; font-size: 10pt;"><u>Schedule</u></font><font style="font-size: 10pt;"><u> 8.2.2(e)</u> &#8211; Prior Agreements</font></div>
              </td>
            </tr>

        </table>
        <div> <br>
        </div>
      </div>
      <div id="DSPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
        <div id="DSPFPageNumberArea" style="text-align: center;"><font id="DSPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">62</font></div>
        <div id="DSPFPageBreak" 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 style="width: 100%;" id="DSPFPageHeader">Confidential</div>
      </div>
      <div style="text-align: center; font-variant: small-caps; font-weight: bold;"><a name="z_Ref243386777"></a><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;">For purposes of this Agreement, the following capitalized terms will have the following meanings:</div>
      <div>&#160;</div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">Acceptance</font>&#8221; means, with respect to an NDA, MAA or JNDA filed for a Product, (a) in the United States, the receipt of written notice from the FDA in
        accordance with 21 C.F.R. &#167;314.101(a)(2) that such NDA is officially &#8220;<font style="font-style: italic;">filed</font>,&#8221; (b) in the European Union, receipt by JBI of written notice of acceptance by the EMA of such MAA for filing under the centralized
        European procedure in accordance with any feedback received from European Regulatory Authorities; <font style="font-style: italic;">provided that</font> if the centralized filing procedure is not used, then Acceptance will be determined upon the
        acceptance of such MAA by the applicable Regulatory Authority in a Major Country in the EU, and (c) in Japan, receipt by JBI of written notice of acceptance of filing of such JNDA from the Koseisho (<u>i.e.</u><font style="font-style: italic;">,</font>
        the Japanese Ministry of Health and Welfare, or any successor agency thereto).</div>
      <div>&#160;</div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">Additional Core IP</font>&#8221; means Third Party intellectual property that is necessary to [***<u>]</u><font style="font-style: italic;">; provided</font> Additional
        Core IP does not include any Patent Rights claiming (or intellectual property related to) [***].</div>
      <div>&#160;</div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">Affiliate</font>&#8221; of an entity means any corporation, firm, partnership or other entity which directly or indirectly through one or more intermediaries controls,
        is controlled by or is under common control with a Party to this Agreement.&#160; An entity will be deemed to control another entity if it (i) owns, directly or indirectly, at least 50% of the outstanding voting securities or capital stock (or such
        lesser percentage which is the maximum allowed to be owned by a foreign corporation in a particular jurisdiction) of such other entity, or has other comparable ownership interest with respect to any entity other than a corporation; or (ii) has the
        power, whether pursuant to contract, ownership of securities or otherwise, to direct the management and policies of the entity.&#160; For clarity, Regulus Therapeutics Inc. will not be deemed an &#8220;<font style="font-style: italic;">Affiliate</font>&#8221; of
        Isis for the purposes of this Agreement under any circumstances.</div>
      <div>&#160;</div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">Agreement</font>&#8221; has the meaning set forth in the Preamble of this Agreement.</div>
      <div>&#160;</div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">Agreement</font>&#160;<font style="font-weight: bold; font-style: italic;">Term</font>&#8221; has the meaning set forth in <u>Section 10.1</u>.</div>
      <div>&#160;</div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">Alliance Manager</font>&#8221; has the meaning set forth in <u>Section 1.6.5</u>.</div>
      <div>&#160;</div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">Annual</font>&#8221; means the period covering a Calendar Year or occurring once per Calendar Year, as the context requires.</div>
      <div>&#160;</div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">API</font>&#8221; means the bulk active pharmaceutical ingredient manufactured in accordance with GMP (unless expressly stated otherwise) for a Product.</div>
      <div>&#160;</div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">Applicable Law</font>&#8221; or &#8220;<font style="font-weight: bold; font-style: italic;">Law</font>&#8221; means all applicable laws, statutes, rules, regulations and other
        pronouncements having the effect of law of any federal, national, multinational, state, provincial, county, city or other political subdivision, agency or other body, domestic or foreign, including any applicable rules, regulations, guidelines, or
        other requirements of the Regulatory Authorities that may be in effect from time to time.</div>
      <div style="text-align: justify;"> <br>
      </div>
      <div id="DSPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
        <div id="DSPFPageNumberArea" style="text-align: center;"><font id="DSPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">63</font></div>
        <div id="DSPFPageBreak" style="page-break-after: always;">
          <hr style="border-width: 0px; clear: both; margin: 4px 0px; width: 100%; height: 2px; color: #000000; background-color: #000000;" noshade="noshade"></div>
        <div style="width: 100%;" id="DSPFPageHeader">Confidential</div>
      </div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">Approval</font>&#8221; means, with respect to a Product in any regulatory jurisdiction, approval from the applicable Regulatory Authority sufficient for the
        manufacture, distribution, use, marketing and sale of such Product in such jurisdiction in accordance with Applicable Laws.&#160; In jurisdictions where the applicable Regulatory Authority sets the pricing or reimbursement authorizations necessary for
        the general marketing and sale of such Product in the marketplace, Approval will not be deemed to have occurred if the final approval to market and sell such Product is being withheld because JBI (or its Affiliate or Sublicensee) and the Regulatory
        Authority have not yet determined pricing or reimbursement even if all other approvals, licenses, registrations or authorizations necessary for marketing, sale or use of such Product in such jurisdiction have been obtained.&#160; &#8220;Approval&#8221; does not
        include authorization by a Regulatory Authority to conduct named patient, compassionate use or other similar activities.</div>
      <div>&#160;</div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">ASO</font>&#8221; means a single-stranded or double-stranded oligonucleotide compound, or analog, variant, mimic, or mimetic thereof, having a sequence that is at least
        six bases long and is designed to hybridize to a nucleic acid transcript via the binding, partially or wholly, of such compound to the nucleic acid transcript.</div>
      <div>&#160;</div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">Audit Report</font>&#8221; has the meaning set forth in <u>Section 6.12</u>.</div>
      <div>&#160;</div>
      <div style="text-align: justify; font-size: 12pt;"><font style="font-weight: bold; font-style: italic; font-size: 10pt;">&#8220;Autoimmune Diseases&#8221;</font><font style="font-size: 10pt;"> is any of a number of diseases characterized by abnormal functioning
          of the immune system which causes the immune system to attack the body&#8217;s own tissues. Crohn&#8217;s disease and ulcerative Colitis which are inflammatory bowel diseases are included as autoimmune diseases for purposes of this Agreement.</font></div>
      <div>&#160;</div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">Bankruptcy Code</font>&#8221; has the meaning set forth in <u>Section 7.12</u>.</div>
      <div>&#160;</div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">Breaching Party</font>&#8221; means the Party that is believed by the Non-Breaching Party to be in material breach of this Agreement.</div>
      <div>&#160;</div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">Business Day</font>&#8221; means any day other than a Saturday or Sunday on which banking institutions in New York, New York are open for business.</div>
      <div>&#160;</div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">Calendar Quarter</font>&#8221; means a financial quarter based on the J&amp;J Universal Calendar for that year (a copy of which is attached hereto as <font style="font-variant: small-caps;"><u>Appendix 3</u></font>) and is used for JBI&#8217;s internal and external reporting purposes; provided, however, that the first Calendar Quarter for the first Calendar Year extends from the Effective Date to the end
        of the then current Calendar Quarter and the last Calendar Quarter extends from the first day of such Calendar Quarter until the effective date of the termination or expiration of the Agreement.</div>
      <div>&#160;</div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">Calendar Year</font>&#8221; means a year based on the J&amp;J Universal Calendar for that year.&#160; The Last Calendar Year of the Term begins on the first day of the
        J&amp;J Universal Calendar Year for the year during which termination or expiration of the Agreement will occur, and the last day of such Calendar Year will be the effective date of such termination or expiration.</div>
      <div>&#160;</div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">Claims</font>&#8221; has the meaning set forth in <u>Section 9.1</u>.</div>
      <div>&#160;</div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">Clinical Study</font>&#8221; or &#8220;<font style="font-weight: bold; font-style: italic;">Clinical Studies</font>&#8221; means a Phase I Clinical Trial, Phase II Clinical Trial,
        Phase III Clinical Trial or Phase IV Clinical Trial, or such other <font style="color: rgb(0, 0, 0);">study in humans that is conducted in accordance with good clinical practices and is designed to generate data in support or maintenance of an
          NDA, MAA or other similar marketing application.</font></div>
      <div style="text-align: justify;"><font style="color: #000000;"> <br>
        </font></div>
      <div id="DSPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
        <div id="DSPFPageNumberArea" style="text-align: center;"><font id="DSPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">64</font></div>
        <div id="DSPFPageBreak" style="page-break-after: always;">
          <hr style="border-width: 0px; clear: both; margin: 4px 0px; width: 100%; height: 2px; color: #000000; background-color: #000000;" noshade="noshade"></div>
        <div style="width: 100%;" id="DSPFPageHeader">Confidential</div>
      </div>
      <div style="text-align: justify; color: rgb(0, 0, 0);">&#8220;<font style="font-weight: bold; font-style: italic;">Clinical Supplies</font>&#8221; means API and finished drug Product for use in a Clinical Study.</div>
      <div>&#160;</div>
      <div style="text-align: justify; color: rgb(0, 0, 0);">&#8220;<font style="font-weight: bold; font-style: italic;">CMO</font>&#8221; means a Third Party contract manufacturer Manufacturing API, Clinical Supplies or Finished Drug Product for any purpose under
        this Agreement.</div>
      <div>&#160;</div>
      <div style="text-align: justify; color: rgb(0, 0, 0);">&#8220;<font style="font-weight: bold; font-style: italic;">Collaboration Target</font>&#8221; means a gene target designated as a Collaboration Target pursuant to <u>Section 1.2.</u></div>
      <div>&#160;</div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">Commercialize</font>,&#8221; &#8220;<font style="font-weight: bold; font-style: italic;">Commercialization</font>&#8221; or &#8220;<font style="font-weight: bold; font-style: italic;">Commercializing</font>&#8221;
        means any and all activities directed to marketing, promoting, detailing, distributing, importing, having imported, exporting, having exported, selling or offering to sell a Product following receipt of Approval for such Product in the applicable
        country, including conducting pre-and post-Approval activities, including studies reasonably required to increase the market potential of the Product and studies to provide improved formulation and Product delivery, and launching and promoting such
        Product in each country.</div>
      <div>&#160;</div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">Commercializing Party</font>&#8221; means (a) JBI, with respect to a Product that is being Developed and Commercialized by or on behalf of JBI, its Affiliates or
        Sublicensees hereunder, and (b) Isis, with respect to a Discontinued Product that is being Developed and Commercialized by or on behalf of Isis, its Affiliates or Sublicensees hereunder.</div>
      <div>&#160;</div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">Commercially Reasonable Efforts</font>&#8221; means the carrying out of discovery, research, development or commercialization activities using good-faith commercially
        reasonable and diligent efforts that the applicable Party would reasonably devote to a compound or product of similar market potential or profit potential at a similar stage in development or product life resulting from its own research efforts,
        based on conditions then prevailing and taking into account, without limitation, issues of safety and efficacy, regulatory authority-approved labeling, product profile, the competitiveness of alternative products in the marketplace, the likely
        timing of the product&#8217;s entry into the market, the patent and other proprietary position, the likelihood of Approval and other relevant scientific, technical and commercial factors.&#160; Without limiting any of the foregoing, Commercially Reasonable
        Efforts as it applies to JBI&#8217;s Development or Commercialization of a Product hereunder includes the use of Commercially Reasonable Efforts to perform the &#8220;<font style="font-style: italic;">General Activities</font>&#8221; described in <font style="font-variant: small-caps;"><u>Schedule 5.2</u></font>, and Commercially Reasonable Efforts as it applies to Isis&#8217; Development of a Product hereunder includes use of Commercially Reasonable Efforts to adhere to the activities and timelines
        set forth in each Drug Discovery Plan and Development Plan.</div>
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      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">Competitive Infringement</font>&#8221; has the meaning set forth in <u>Section 7.5.1</u>.</div>
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      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">Completion of PoC</font>&#8221; means, on a Product-by-Product basis, when JBI receives the primary end-point data generated under the statistical analysis plan of the
        first PoC Study.</div>
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      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">Compound</font>&#8221; means on a Drug Discovery Program-by-Drug Discovery Program basis, any ASO that is designed to bind to the RNA that encodes the applicable
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      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">Confidential Information</font>&#8221; has the meaning set forth in <u>Section 11.1</u>.&#160; &#8220;<font style="font-style: italic;">Confidential Information</font>&#8221; does not
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              <div>was in the lawful knowledge and possession of the Receiving Party or its Affiliates prior to the time it was disclosed to, or learned by, the Receiving Party or its Affiliates, or was otherwise developed independently by the Receiving
                Party or its Affiliates, as evidenced by written records kept in the ordinary course of business, or other documentary proof of actual use by the Receiving Party or its Affiliates;</div>
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              <div>was generally available to the public or otherwise part of the public domain at the time of its disclosure to the Receiving Party or its Affiliates;</div>
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              <div>became generally available to the public or otherwise part of the public domain after its disclosure and other than through any act or omission of the Receiving Party or its Affiliates in breach of this Agreement; or</div>
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            <td style="width: 36pt; vertical-align: top; font-weight: bold;">(d)</td>
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              <div>was disclosed to the Receiving Party or its Affiliates, other than under an obligation of confidentiality, by a Third Party who had no obligation to the Disclosing Party or its Affiliates not to disclose such information to others.</div>
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      <div>&#160;</div>
      <div style="text-align: justify;">&#8220;<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 possession of the ability to grant a license or sublicense
        hereunder without violating the terms of any agreement with any Third Party; <font style="font-style: italic;">provided, however</font>, that if a Party has a right to grant a license or sublicense, with respect to an item of intellectual property
        to the other Party only upon payment of compensation (including milestones or royalties) to a Third Party (&#8220;<font style="font-weight: bold; font-style: italic;">Third Party Compensation</font>&#8221;) (other than Isis Supported Pass-Through Costs in the
        case of Isis, and other than JBI Supported Pass-Through Costs in the case of JBI), then the first Party will be deemed to have &#8220;<font style="font-style: italic;">Control</font>&#8221; of the relevant item of intellectual property only if the other Party
        agrees to bear the cost of such Third Party Compensation.&#160; Notwithstanding anything to the contrary under this Agreement, with respect to any Third Party that becomes an Affiliate of a Party after the Effective Date (including a Third Party
        acquirer), no intellectual property of such Third Party will be included in the licenses granted hereunder by virtue of such Third Party becoming an Affiliate of such Party.</div>
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      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">Cover</font>,&#8221; &#8220;<font style="font-weight: bold; font-style: italic;">Covered</font>&#8221; or &#8220;<font style="font-weight: bold; font-style: italic;">Covering</font>&#8221;
        means, with respect to a patent, that, but for a license under such patent, the act of making, using or selling would infringe a Valid Claim included in such patent, or in the case of a patent that is a patent application, would infringe a Valid
        Claim in such patent application if it were to issue as a patent.</div>
      <div>&#160;</div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">CREATE Act</font>&#8221; means the Cooperative Research and Technology Enhancement Act of 2004, 35 U.S.C. &#167; 103(c)(2)-(c)(3).</div>
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      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">CTD</font>&#8221; has the meaning set forth in Section 5.4.1.</div>
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      <div style="text-align: justify; font-size: 12pt;"><font style="font-weight: bold; font-style: italic; font-size: 10pt;">&#8220;Currency Hedge Rate(s)&#8221;</font><font style="font-size: 10pt;"> is calculated as a weighted average hedge rate of the outstanding
          external foreign currency forward hedge contract(s) of Johnson &amp; Johnson&#8217;s Global Treasury Services Center (GTSC) and its Affiliates with third party banks. The hedge contract(s) is entered into to protect the transactional foreign exchange
          risk exposures of JBI by reducing the impact of foreign currency volatility through a systematic buildup of a yearly Currency Hedge Rate(s).</font></div>
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        </font></div>
      <div id="DSPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
        <div id="DSPFPageNumberArea" style="text-align: center;"><font id="DSPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">66</font></div>
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      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">Develop</font>,&#8221; &#8220;<font style="font-weight: bold; font-style: italic;">Developing</font>&#8221; or &#8220;<font style="font-weight: bold; font-style: italic;">Development</font>&#8221;
        means with respect to a Product, any and all discovery, characterization, or preclinical (including IND-Enabling Toxicology Studies), clinical, or regulatory activity with respect to the Product to seek Approval (including the submission of all
        necessary filings with applicable Regulatory Authorities to support such preclinical and clinical activities and Approval), including human clinical trials conducted after Approval of the Product to seek Approval for additional indications for the
        Product.</div>
      <div>&#160;</div>
      <div style="text-align: justify; font-size: 12pt;"><font style="font-weight: bold; font-style: italic; font-size: 10pt;">&#8220;Development Candidate</font><font style="font-size: 10pt;">&#8221; means a Compound that is reasonably determined by Isis&#8217; Research
          Management Committee in accordance with Isis&#8217; standard procedures for designating development candidates (and giving good faith consideration to the input of JBI&#8217;s representatives on the JRC) as ready to start IND-Enabling Toxicology Studies.&#160;
          The checklist Isis uses as of the Effective Date when reviewing potential development candidates for approval is attached hereto as <font style="font-variant: small-caps;"><u>Appendix 2</u></font>.</font></div>
      <div>&#160;</div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">Development Candidate Data Package</font>&#8221; means, with respect to a Development Candidate: [***].</div>
      <div>&#160;</div>
      <div style="text-align: justify; color: rgb(0, 0, 0);">&#8220;<font style="font-weight: bold; font-style: italic;">Development Plan</font>&#8221; has the meaning set forth in <u>Section 1.3.2(b)</u>.</div>
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      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">Disclosing Party</font>&#8221; has the meaning set forth in <u>Section 11.1</u>.</div>
      <div>&#160;</div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">Discontinued Product</font>&#8221; means a Product that is the subject of a termination under this Agreement.</div>
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      <div style="text-align: justify; font-size: 12pt;"><font style="font-weight: bold; font-style: italic; font-size: 10pt;">&#8220;Dispositive Rejection Condition&#8221; </font><font style="font-size: 10pt;">has the meaning set forth in <u>Section 1.2.3</u>.</font></div>
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      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">Dispute</font>&#8221; means any dispute arising between the Parties relating to, arising out of or in any way connected with this Agreement or any term or condition
        hereof, or the performance by either Party of its obligations hereunder, whether before or after termination of this Agreement that cannot be resolved by the Parties.</div>
      <div>&#160;</div>
      <div style="text-align: justify; color: rgb(0, 0, 0);">&#8220;<font style="font-weight: bold; font-style: italic;">Drug Discovery Plan</font>&#8221; has the meaning set forth in <u>Section 1.3.2(b)</u>.</div>
      <div>&#160;</div>
      <div style="text-align: justify; color: rgb(0, 0, 0);">&#8220;<font style="font-weight: bold; font-style: italic;">Drug Discovery Program</font>&#8221; has the meaning set forth in <u>Section 1.2</u>.</div>
      <div>&#160;</div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">Drug Discovery Term</font>&#8221; has the meaning set forth in Section 1.5.1.</div>
      <div>&#160;</div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">Effective Date</font>&#8221; has the meaning set forth in the Preamble of this Agreement.</div>
      <div>&#160;</div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">EMA</font>&#8221; means the European Medicines Agency and any successor entity thereto.</div>
      <div>&#160;</div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">European Union</font>&#8221; or &#8220;<font style="font-weight: bold; font-style: italic;">EU</font>&#8221; means each and every country or territory that is officially part of
        the European Union.</div>
      <div>&#160;</div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">Executives</font>&#8221; has the meaning set forth in Section 12.1.1.</div>
      <div>&#160;</div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">FDA</font>&#8221; means the United States Food and Drug Administration and any successor entity thereto.</div>
      <div style="text-align: justify;"> <br>
      </div>
      <div id="DSPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
        <div id="DSPFPageNumberArea" style="text-align: center;"><font id="DSPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">67</font></div>
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      </div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">Field</font>&#8221; means, except as may be limited under Section 4.1.4, the prophylactic or therapeutic use or form of administration of a Product for any indication.</div>
      <div>&#160;</div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">Finished Drug Product</font>&#8221; means any drug product containing API as an active ingredient in finished bulk form for the Development or Commercialization by a
        Party under this Agreement.</div>
      <div>&#160;</div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">First Commercial Sale</font>&#8221; means with respect to a Product, the first sale of such Product by JBI, its Affiliate or its Sublicensee to a Third Party in a
        particular country after Approval of the Product has been obtained in such country.</div>
      <div>&#160;</div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">Follow-On Agreement</font>&#8221; has the meaning set forth in Section 2.1.2.</div>
      <div>&#160;</div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">Follow-On Compound</font>&#8221; means, with respect to a given Compound for a given Collaboration Target, any ASO (other than the Development Candidate for such
        Collaboration Target) that is designed to bind to the RNA that encodes such Collaboration Target discovered by or on behalf of Isis following exercise of the applicable Option by JBI.</div>
      <div>&#160;</div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">FTE</font>&#8221; means a total of 47 weeks or 1880 hours per year of work on the Development, Manufacturing or Commercialization of a Product carried out by employees
        of a Party having the appropriate relevant expertise to conduct such activities.</div>
      <div>&#160;</div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">FTE Rate</font>&#8221; Means for a given Calendar Year the rate that Isis charges for a full time equivalent [***].</div>
      <div>&#160;</div>
      <div style="text-align: justify; font-size: 12pt;"><font style="font-weight: bold; font-style: italic; font-size: 10pt;">&#8220;Fully Absorbed Cost of Goods</font><font style="font-size: 10pt;">&#8221; means the reasonable and necessary internal and third party
          costs with no mark-up incurred by Isis in making or acquiring of product as determined using the methodology set forth in <font style="font-variant: small-caps;">Schedule 4.4.4</font> fairly applied and as employed on a consistent basis
          throughout Isis&#8217; operations and shall not include inter-company profits among Isis and its Affiliates. <font style="font-variant: small-caps;">.</font></font></div>
      <div>&#160;</div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">GCP</font>&#8221; means the then current standards for clinical trials for pharmaceuticals, as set forth in the United States Code of Federal Regulations, ICH
        guidelines and applicable regulations, laws or rules as promulgated thereunder.</div>
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      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">Generic Product</font>&#8221; means, with respect to a particular Product in a country, a generic or biosimilar pharmaceutical product, that is not produced, licensed
        or owned by JBI or any of its Affiliates, that:(a) contains the same, or a bioequivalent of the, active ingredient as a Product; and (b) is approved for use in such country by a regulatory authority through a regulatory pathway by referencing
        clinical data first submitted for obtaining regulatory approval for such Product.&#160; Generic Product includes any pharmaceutical products obtained via a bioequivalence or bioavailability showing such as those covered by section 505(b)(2) or under
        505(j) of the U.S. Federal Food, Drug, and Cosmetic Act or an equivalent outside the United States.</div>
      <div>&#160;</div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">GLP</font>&#8221; means the then-current good laboratory practice standards promulgated or endorsed by the FDA as defined in 21 C.F.R. Part 58, and comparable foreign
        regulatory standards.</div>
      <div style="text-align: justify;"> <br>
      </div>
      <div id="DSPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
        <div id="DSPFPageNumberArea" style="text-align: center;"><font id="DSPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">68</font></div>
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      </div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">GMP</font>&#8221; means current Good Manufacturing Practices as specified in the United States Code of Federal Regulations, ICH Guideline Q7A, or equivalent laws,
        rules, or regulations of an applicable Regulatory Authority at the time of manufacture.</div>
      <div>&#160;</div>
      <div style="text-align: justify;">&#160;&#8220;[***<u>]</u>.</div>
      <div>&#160;</div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">IND</font>&#8221; means an Investigational New Drug Application (as defined in the Food, Drug and Cosmetic Act, as amended) filed with the FDA or its foreign
        counterparts.</div>
      <div>&#160;</div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">IND-Enabling Toxicology Studies</font>&#8221; means the pharmacokinetic and toxicology studies required to meet the requirements for filing an IND.&#160; IND-Enabling
        Toxicology Studies do not include chronic toxicology studies or reproductive toxicology studies.</div>
      <div>&#160;</div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">Indemnitee</font>&#8221; has the meaning set forth in Section 9.3.</div>
      <div>&#160;</div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">Indication</font>&#8221; means distinct, well-categorized disease or condition in humans for which a separate marketing authorization (or amendment to a marketing
        authorization) is required.</div>
      <div>&#160;</div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">Initiation</font>&#8221; or &#8220;<font style="font-weight: bold; font-style: italic;">Initiate</font>&#8221; means, with respect to any IND-Enabling Toxicology Study, dosing of
        the first animal subject in such IND-Enabling Toxicology Study and, with respect to any Clinical Study, dosing of the first human subject in such Clinical Study.</div>
      <div>&#160;</div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">Integrated Development Plan</font>&#8221; or &#8220;<font style="font-weight: bold; font-style: italic;">IDP</font>&#8221; has the meaning set forth in Section 5.3.</div>
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      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">Isis</font>&#8221; has the meaning set forth in the Preamble of this Agreement.</div>
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      <div style="text-align: justify;"><a name="z_Ref187257823"></a>&#8220;<font style="font-weight: bold; font-style: italic;">Isis Core Technology Patents</font>&#8221; means all Patent Rights owned, used, developed by, or licensed to Isis or its Affiliates, in
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        Analytical Patents.&#160; A list of Isis Core Technology Patents as of the Effective Date is set forth on <font style="font-variant: small-caps;">Schedule </font>8.2.2(a) attached hereto.</div>
      <div>&#160;</div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">Isis Formulation Patents</font>&#8221; means the Patent Rights listed on Schedule 8.2.2(d) attached hereto.</div>
      <div>&#160;</div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">Isis In-License Agreements</font>&#8221; has the meaning set forth in Section 6.9.1(a).</div>
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      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">Isis Internal ASO Safety Database</font>&#8221; has the meaning set forth in Section 5.6.</div>
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      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">Isis Know-How</font>&#8221; means any Know-How, including any Jointly-Owned Program Know-How and Isis Program Know-How, owned, used, developed by, or licensed to Isis
        or its Affiliates, in each case to the extent Controlled by Isis or its Affiliates on the Effective Date or at any time during the Agreement Term.&#160; Isis Know-How does not include the Isis Manufacturing and Analytical Know-How.</div>
      <div>&#160;</div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">Isis Manufacturing and Analytical Know-How</font>&#8221; means Know-How, including Jointly-Owned Program Know-How, that relates to the synthesis or analysis of a
        Product regardless of sequence or chemical modification, owned, used, developed by, or licensed to Isis or its Affiliates, in each case to the extent Controlled by Isis or its Affiliates on the Effective Date or at any time during the Agreement
        Term.&#160; Isis Manufacturing and Analytical Know-How does not include the Isis Know-How.</div>
      <div style="text-align: justify;"> <br>
      </div>
      <div id="DSPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
        <div id="DSPFPageNumberArea" style="text-align: center;"><font id="DSPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">69</font></div>
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      </div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">Isis Manufacturing and Analytical Patents</font>&#8221; means Patent Rights, including Jointly-Owned Program Patents, that claim methods and materials used in the
        synthesis or analysis of a Product regardless of sequence or chemical modification, owned, used, developed by, or licensed to Isis or its Affiliates, in each case to the extent Controlled by Isis or its Affiliates on the Effective Date or at any
        time during the Agreement Term.&#160; A list of Isis Manufacturing and Analytical Patents as of the Effective Date is set forth on <font style="font-variant: small-caps;">Schedule </font>8.2.2(b) attached hereto.&#160; Isis Manufacturing and Analytical
        Patents do not include the Isis Product-Specific Patents or the Isis Core Technology Patents.</div>
      <div>&#160;</div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">Isis Platform Technology</font>&#8221; has the meaning set forth in Section 8.2.2.</div>
      <div>&#160;</div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">Isis Product-Specific Patents</font>&#8221; means all Product-Specific Patents, in each case to the extent Controlled by Isis or its Affiliates on the Effective Date or
        at any time during the Agreement Term.&#160; A list of Isis Product-Specific Patents as of the Effective Date is set forth on <font style="font-variant: small-caps;">Schedule </font>8.2.2(c) attached hereto.</div>
      <div>&#160;</div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">Isis Program Know-How</font>&#8221; has the meaning set forth in Section 7.1.2.</div>
      <div>&#160;</div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">Isis Program Patents</font>&#8221; has the meaning set forth in Section 7.1.2.</div>
      <div>&#160;</div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">Isis Supported Pass-Through Costs</font>&#8221; means [***].</div>
      <div>&#160;</div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">JBI</font>&#8221; has the meaning set forth in the Preamble of this Agreement.</div>
      <div>&#160;</div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">JBI Royalty</font>&#8221; has the meaning set forth in <u>Section 6.8.1</u>.</div>
      <div>&#160;</div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">JBI Know-How</font>&#8221; means any Know-How owned, used, developed by, or licensed to JBI or its Affiliates, in each case to the extent Controlled by JBI or its
        Affiliates on the Effective Date or at any time during the Agreement Term, <font style="font-style: italic;">but specifically excluding</font> the JBI Program Know-How.</div>
      <div>&#160;</div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">JBI Patents</font>&#8221; means any Patent Rights included in the JBI Technology.</div>
      <div>&#160;</div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">JBI Product-Specific Patents</font>&#8221; means all Product-Specific Patents owned, used, developed by, or licensed to JBI or its Affiliates, in each case to the
        extent Controlled by JBI or its Affiliates on the Effective Date or at any time during the Agreement Term.</div>
      <div>&#160;</div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">JBI Program Know-How</font>&#8221; has the meaning set forth in <u>Section 7.1.2</u>.</div>
      <div>&#160;</div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">JBI Program Patents</font>&#8221; has the meaning set forth in <u>Section 7.1.2</u>.</div>
      <div>&#160;</div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">JBI Program Technology</font>&#8221; has the meaning set forth in <u>Section 7.1.2</u>.</div>
      <div>&#160;</div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">JBI-Prosecuted Patents</font>&#8221; has the meaning set forth in <u>Section 7.2.4</u>.</div>
      <div>&#160;</div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">JBI Supported Pass-Through Costs</font>&#8221; means [***].</div>
      <div style="text-align: justify;"> <br>
      </div>
      <div id="DSPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
        <div id="DSPFPageNumberArea" style="text-align: center;"><font id="DSPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">70</font></div>
        <div id="DSPFPageBreak" style="page-break-after: always;">
          <hr style="border-width: 0px; clear: both; margin: 4px 0px; width: 100%; height: 2px; color: #000000; background-color: #000000;" noshade="noshade"></div>
        <div style="width: 100%;" id="DSPFPageHeader">Confidential</div>
      </div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">JBI Technology</font>&#8221; means the JBI Program Technology, Jointly-Owned Program Technology, JBI Product-Specific Patents and any trademarks described in <u>Section


          4.1.5</u>, owned, used, developed by, or licensed to JBI or its Affiliates that is necessary or useful to Develop, register, Manufacture or Commercialize a Product.</div>
      <div>&#160;</div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">Japan NDA</font>&#8221; or &#8220;<font style="font-weight: bold; font-style: italic;">JNDA</font>&#8221; means the Japanese equivalent of an NDA filed with the Koseisho (i.e.<font style="font-style: italic;">,</font> the Japanese Ministry of Health and Welfare, or any successor agency thereto).</div>
      <div>&#160;</div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">JNDA Approval</font>&#8221; means the Approval of a JNDA by the Koseisho (i.e.<font style="font-style: italic;">,</font> the Japanese Ministry of Health and Welfare, or
        any successor agency thereto) for the applicable Product in Japan including pricing.</div>
      <div>&#160;</div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">Joint Patent Committee</font>&#8221; or &#8220;<font style="font-weight: bold; font-style: italic;">JPC</font>&#8221; has the meaning set forth in Section 7.1.3(a).</div>
      <div>&#160;</div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">Jointly-Owned Program Know-How</font>&#8221; has the meaning set forth in Section 7.1.2.</div>
      <div>&#160;</div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">Jointly-Owned Program Patents</font>&#8221; has the meaning set forth in Section 7.1.2.</div>
      <div>&#160;</div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">Jointly-Owned Program Technology</font>&#8221; has the meaning set forth in Section 7.1.2.</div>
      <div>&#160;</div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">JRC</font>&#8221; has the meaning set forth in Section 1.6.1.</div>
      <div>&#160;</div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">Know-How</font>&#8221; means inventions, technical information, know-how and materials, including technology, data, compositions, formulas, biological materials,
        assays, reagents, constructs, compounds, discoveries, procedures, processes, practices, protocols, methods, techniques, results of experimentation or testing, knowledge, trade secrets, skill and experience, in each case whether or not patentable or
        copyrightable, and in each case that are unpatented.</div>
      <div>&#160;</div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">Lead Party</font>&#8221; has the meaning set forth in Section 7.4.1.</div>
      <div>&#160;</div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">Licensed Know-How</font>&#8221; means Isis Manufacturing and Analytical Know-How, and Isis Know-How.&#160; For clarity, Licensed Know-How does not include any Know-How
        covering delivery devices.</div>
      <div>&#160;</div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">Licensed Patents</font>&#8221; means the Isis Product-Specific Patents, Isis Core Technology Patents, Isis Manufacturing and Analytical Patents, Isis Formulation
        Patents and Isis&#8217; interest in Jointly-Owned Program Patents.&#160; For clarity, Licensed Patents do not include any Patent Rights claiming formulation technology or delivery devices unless such Patent Rights are included in the Jointly-Owned Program
        Patents.</div>
      <div>&#160;</div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">Licensed Technology</font>&#8221; means, on a Product-by-Product basis, any and all Licensed Patents, Licensed Know-How, and any trademarks described in Section 4.1.5,
        to the extent necessary or useful to Develop, register, Manufacture or Commercialize such Product.</div>
      <div>&#160;</div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">Losses</font>&#8221; has the meaning set forth in Section 9.1.</div>
      <div style="text-align: justify;"> <br>
      </div>
      <div id="DSPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
        <div id="DSPFPageNumberArea" style="text-align: center;"><font id="DSPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">71</font></div>
        <div id="DSPFPageBreak" style="page-break-after: always;">
          <hr style="border-width: 0px; clear: both; margin: 4px 0px; width: 100%; height: 2px; color: #000000; background-color: #000000;" noshade="noshade"></div>
        <div style="width: 100%;" id="DSPFPageHeader">Confidential</div>
      </div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">MAA</font>&#8221; means, with respect to a particular Product, a marketing authorization application filed with the EMA after completion of Clinical Studies (excluding
        Phase IV Clinical Trials) to obtain Approval for such Product under the centralized European filing procedure or, if the centralized EMA filing procedure is not used, filed using the applicable procedures in any European Union country.</div>
      <div>&#160;</div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">MAA Approval</font>&#8221; means, with respect to a particular Product, the Approval of an MAA by the EMA for such Product in any country in the EU including pricing.</div>
      <div>&#160;</div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">Major Market</font>&#8221; means any of the following countries: the United States, Japan, the United Kingdom, Germany, France, Italy and Spain.</div>
      <div>&#160;</div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">Manufacture</font>&#8221; or &#8220;<font style="font-weight: bold; font-style: italic;">Manufactured</font>&#8221; or &#8220;<font style="font-weight: bold; font-style: italic;">Manufacturing</font>&#8221;
        means any activity involved in or relating to the manufacturing, quality control testing (including in-process, release and stability testing), releasing or packaging, for pre-clinical and clinical purposes, of API or a Product in finished form.</div>
      <div>&#160;</div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">Milestone Event</font>&#8221; means a Pre-Licensing Milestone Event or a Post-Licensing Milestone Event, as the case may be.</div>
      <div>&#160;</div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">Minimum Third Party Payments</font>&#8221; means [***].</div>
      <div>&#160;</div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">NDA</font>&#8221;<font style="font-weight: bold;">&#160;</font>means a New Drug Application filed with the FDA after completion of Clinical Studies to obtain Approval for a
        Product in the United States.</div>
      <div>&#160;</div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">NDA Approval</font>&#8221; means the Approval of an NDA by the FDA for a Product in the U.S.</div>
      <div>&#160;</div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">Negotiation Period</font>&#8221; has the meaning set forth in Section 2.1.2.</div>
      <div>&#160;</div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">Net Sales</font>&#8221; means the gross amounts invoiced on sales of a Product by JBI or any of its Affiliates or sublicensees to a Third Party purchaser in an
        arms-length transaction, less the following customary deductions, determined in accordance with US generally accepted accounting principles and standard internal policies and procedures and accounting standards consistently applied throughout
        Johnson &amp; Johnson, to the extent specifically and solely allocated to such Product and actually taken, paid, accrued, allowed, included or allocated based on good faith estimates in the gross sales prices with respect to such sales (and
        consistently applied as set forth below):<a name="z_Ref242086466"></a></div>
      <div>&#160;</div>
      <table id="z4d9479c1752f4a129b44d85f38e4ee8f" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 18pt; vertical-align: top;">a)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>normal and customary trade, cash and/or quantity discounts, allowances, and credits allowed or paid, in the form of deductions actually allowed or fees actually paid with respect to sales of such Product (to the extent not already
                reflected in the amount invoiced) excluding commissions for commercialization;</div>
            </td>
          </tr>

      </table>
      <table id="zb5ba651f7bd44e6eb42f91e8eb5cb607" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 18pt; vertical-align: top;">b)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div> excise taxes, use taxes, tariffs, sales taxes and customs duties, and/or other government charges imposed on the sale of Product to the extent included in the price and separately itemized on the invoice price (but specifically
                excluding, for clarity, any income taxes assessed against the income arising from such sale) (including VAT, but only to the extent that such VAT taxes are not reimbursable or refundable);</div>
            </td>
          </tr>

      </table>
      <table id="ze34b386f345149d6b18cf1e9dfd8ebcf" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 18pt; vertical-align: top;">c)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>outbound freight, shipment and insurance costs to the extent included in the price and separately itemized on the invoice price;<a name="z_Ref242086468"></a></div>
            </td>
          </tr>

      </table>
      <div> <br>
      </div>
      <div id="DSPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
        <div id="DSPFPageNumberArea" style="text-align: center;"><font id="DSPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">72</font></div>
        <div id="DSPFPageBreak" style="page-break-after: always;">
          <hr style="border-width: 0px; clear: both; margin: 4px 0px; width: 100%; height: 2px; color: #000000; background-color: #000000;" noshade="noshade"></div>
        <div style="width: 100%;" id="DSPFPageHeader">Confidential</div>
      </div>
      <table id="z1f7b77ed197b4a08b4574e97b77a3f9f" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 18pt; vertical-align: top;">d)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>compulsory payments and cash rebates related to the sales of such Product paid to a Governmental Authority (or agent thereof) pursuant to governmental regulations by reason of any national or local health insurance program or similar
                program, to the extent allowed and taken; including Government levied fees as a result of Healthcare Reform policies</div>
            </td>
          </tr>

      </table>
      <table id="z15c8243e33c443f4bed43823e1dd8f64" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 18pt; vertical-align: top;">e)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>retroactive price reductions, credits or allowances actually granted upon rejections or returns of Product, including for recalls or damaged good and billing errors; and</div>
            </td>
          </tr>

      </table>
      <table id="z5c3d73768f8d46aeabcafe99ca5bc4d3" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 18pt; vertical-align: top;">f)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>rebates, chargebacks, and discounts (or equivalent thereof) actually granted to managed health care organizations, pharmacy benefit managers (or equivalent thereof), federal, state/provincial, local or other governments, or their
                agencies or purchasers, reimbursers, or trade customers.</div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <div style="margin-left: 54pt;">The sales of Products arising from named patient, compassionate use, or other similar programs will not be considered a First Commercial Sale for purposes of calculating the Royalty Period.</div>
      <div><br>
      </div>
      <div style="text-align: justify; margin-left: 54pt;">All aforementioned deductions shall only be allowable to the extent they are commercially reasonable and shall be determined, on a country-by-country basis, as incurred in the ordinary course of
        business in type and amount consistent with the Party&#8217;s, the Affiliate&#8217;s, or Third Party sublicensee&#8217;s (as the case may be) business practices consistently applied across its product lines and accounting standards and verifiable based on the
        Johnson &amp; Johnson sales reporting system.&#160; All such discounts, allowances, credits, rebates, and other deductions shall be fairly and equitably allocated to Product and other products of the Party and its Affiliates and sublicensees such that
        Product does not bear a disproportionate portion of such deductions.</div>
      <div><br>
      </div>
      <div style="text-align: justify; margin-left: 54pt;"><u>The following shall be excluded&#160; for the purposes of calculating royalties&#160; or sales milestones:</u></div>
      <div style="text-align: justify; margin-left: 54pt;"><u> <br>
        </u></div>
      <table id="z434380a268664082ba2b4c9358da551f" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 18pt; vertical-align: top;">a)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>Sales of Product by and between JBI and its Affiliates and sublicenses so long as such Product is subsequently resold to a Third-party end user where such resale to such Third-party end user is included in Net Sales</div>
            </td>
          </tr>

      </table>
      <table id="zc703b939d9114ff8ae8629a2f29f6d0b" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 18pt; vertical-align: top;">b)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>Sales of Product for the use in conducting clinical trials,&#160; pre-clinical studies or other research or development activities in a country in order to obtain&#160; Regulatory Approval of Product in such country</div>
            </td>
          </tr>

      </table>
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          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 18pt; vertical-align: top;">c)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>Product provided free of charge for a <font style="font-style: italic;">bona fide</font> charitable purpose</div>
            </td>
          </tr>

      </table>
      <table id="z36e8f4fa4f2849a88e1e4d28a1713535" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 18pt; vertical-align: top;">d)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>Product used for commercially reasonable free sampling programs.</div>
            </td>
          </tr>

      </table>
      <table id="z7517ac7187044b7e8f5ef8d652053750" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 18pt; vertical-align: top;">e)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>Sales of Product free of charge for Compassionate</div>
            </td>
          </tr>

      </table>
      <table id="z4bc1203a47e946e1a5fdc2544ad3e1b9" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 18pt; vertical-align: top;">f)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>Sales of Product for Named Patient Sales where such Product is sold at a significant discount to the proposed price for the Product following Approval.</div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <div id="DSPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
        <div id="DSPFPageNumberArea" style="text-align: center;"><font id="DSPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">73</font></div>
        <div id="DSPFPageBreak" style="page-break-after: always;">
          <hr style="border-width: 0px; clear: both; margin: 4px 0px; width: 100%; height: 2px; color: #000000; background-color: #000000;" noshade="noshade"></div>
        <div style="width: 100%;" id="DSPFPageHeader">Confidential</div>
      </div>
      <div style="text-align: justify; margin-left: 54pt;">In the event Product(s) are sold in combination with other products or services from JBI, its Affiliates or sublicensees and the customer receives a specific discount for such &#8220;bundling&#8221; of
        products (for clarity, this situation describes bundling of two or more separate products, each in finished dosage form, and not a fixed combination of two active pharmaceutical ingredients), the Net Sales of the said Product(s), for the purposes
        of determining royalty payments, shall be determined by multiplying the relevant Net Sales by the fraction, A/(A+B) where A is the weighted (by sales volume) average sale price in a particular country of the Product(s) in the previous Calendar Year
        when sold separately and B is the weighted average sale price in that country in the previous Calendar Year of the other product sold separately. In the event that such average sale price cannot be determined for either of the Product(s) or the
        other product(s) it has been sold with, in combination, then for purposes of determining the royalty payments, JBI will propose a reasonable good faith estimate of the fair market value of each component (and JBI will provide Isis a justification
        and support for such estimates) which will be substituted for the weighted average sales price for each such product in the formula above. If JBI, its Affiliate or a Sublicensee receives non-monetary consideration for a Product, Net Sales are
        calculated based on the fair market value of that consideration.</div>
      <div style="text-align: justify;"><br>
      </div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">New Third Party Licenses</font>&#8221; has the meaning set forth in Section 8.3.2.</div>
      <div>&#160;</div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">Non-Breaching Party</font>&#8221; means the Party that believes the Breaching Party is in material breach of this Agreement.</div>
      <div>&#160;</div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">Option</font>&#8221; has the meaning set forth in Section 3.1.</div>
      <div>&#160;</div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">Option Deadline</font>&#8221; has the meaning set forth in Section 3.1.</div>
      <div>&#160;</div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">Option Period</font>&#8221; means, with respect to a Drug Discovery Program, the period beginning on the date when the applicable Collaboration Target was designated
        and ending on the expiration or earlier termination of the Option with respect to such Drug Discovery Program.</div>
      <div>&#160;</div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">Out-of-Pocket Expenses</font>&#8221; means the amounts paid to Third Party vendors or contractors, for services or materials provided by them directly in the
        performance of activities to the extent such services or materials apply directly to the activities under this agreement.</div>
      <div>&#160;</div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">Party</font>&#8221; or &#8220;<font style="font-weight: bold; font-style: italic;">Parties</font>&#8221; means JBI and Isis individually or collectively.</div>
      <div>&#160;</div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">Patent Costs</font>&#8221; means the reasonable fees and expenses paid to outside legal counsel, and filing, maintenance and other reasonable Out-of-Pocket expenses
        paid to Third Parties, incurred in connection with the Prosecution and Maintenance of Patent Rights.</div>
      <div>&#160;</div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">Patent Rights</font>&#8221; means (a) patents, patent applications and similar government-issued rights protecting inventions in any country or jurisdiction however
        denominated, (b) all priority applications, divisionals, continuations, substitutions, continuations-in-part of and similar applications claiming priority to any of the foregoing, and (c) all patents and similar government-issued rights protecting
        inventions issuing on any of the foregoing applications, together with all registrations, reissues, renewals, re-examinations, confirmations, supplementary protection certificates, and extensions of any of (a), (b) or (c).</div>
      <div style="text-align: justify;"> <br>
      </div>
      <div id="DSPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
        <div id="DSPFPageNumberArea" style="text-align: center;"><font id="DSPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">74</font></div>
        <div id="DSPFPageBreak" style="page-break-after: always;">
          <hr style="border-width: 0px; clear: both; margin: 4px 0px; width: 100%; height: 2px; color: #000000; background-color: #000000;" noshade="noshade"></div>
        <div style="width: 100%;" id="DSPFPageHeader">Confidential</div>
      </div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">Permitted Licenses</font>&#8221; means (1) licenses granted by Isis before or after the Effective Date to any Third Party under the Isis Core Technology Patents, the
        Isis Manufacturing and Analytical Patents, or the Isis Manufacturing and Analytical Know-How (but not under the Isis Product-Specific Patents) to (a) use oligonucleotides (or supply oligonucleotides to end users) solely to conduct pre-clinical
        research, or (b) enable such Third Party to manufacture or formulate oligonucleotides, where (i) such Third Party is primarily engaged in providing contract manufacturing or services and is not primarily engaged in drug discovery, development or
        commercialization of therapeutics; and (ii) Isis does not assist such Third Party to identify, discover or make a Compound or Product; and (2) material transfer, collaboration or sponsored research agreements with academic collaborators or
        non-profit institutions solely to conduct noncommercial research.</div>
      <div>&#160;</div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">Person</font>&#8221; will mean any corporation, limited or general partnership, limited liability company, joint venture, trust, unincorporated association,
        governmental body, authority, bureau or agency, any other entity or body, or an individual.</div>
      <div>&#160;</div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">Phase I Clinical Trial</font>&#8221; means a human clinical trial that is intended to initially evaluate the safety, metabolism and pharmacokinetics of a therapeutic
        agent that would otherwise satisfy the requirements of 21 C.F.R. 312.21(a) or an equivalent clinical trial in a country in the Territory other than the United States.</div>
      <div>&#160;</div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">Phase II Clinical Trial</font>&#8221; means a human clinical trial, for which the primary endpoints include a determination of safety, dose ranges or an indication of
        efficacy of a therapeutic in patients being studied as described in 21 C.F.R. &#167;312.21(b), or an equivalent clinical trial in a country in the Territory other than the United States, and that is prospectively designed to generate sufficient data (if
        successful) to commence pivotal clinical trials.</div>
      <div>&#160;</div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">Phase III Clinical Trial</font>&#8221; means a human clinical trial (regardless of whether actually designated as &#8220;Phase III&#8221;) that is prospectively designed, along
        with other Phase III Clinical Trials, to demonstrate statistically whether a therapeutic is safe and effective for use in humans in the indication being investigated as described in 21 C.F.R. &#167;312.21(c), or an equivalent clinical trial in a country
        in the Territory other than the United States.</div>
      <div>&#160;</div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">Phase IV Clinical Trial</font>&#8221; means, with respect to a Product, (a) any Clinical Study conducted to satisfy a requirement of a Regulatory Authority in order to
        maintain a Regulatory Approval for such Product or (b) any Clinical Study conducted after the first Regulatory Approval in the same disease state for which such Product received Regulatory Approval other than for purposes of obtaining Regulatory
        Approval.</div>
      <div>&#160;</div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">Plan</font>&#8221; means a Drug Discovery Plan and/or Development Plan, as applicable.</div>
      <div>&#160;</div>
      <div style="text-align: justify; font-size: 12pt;"><font style="font-weight: bold; font-style: italic; font-size: 10pt;">&#8220;PoC Study&#8221; </font><font style="font-size: 10pt;">means a study conducted during a Phase II Clinical Trial designed to give
          preliminary evidence of efficacy and safety for a Product.</font></div>
      <div>&#160;</div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">Post-Licensing Milestone Event</font>&#8221; has the meaning set forth in Section 6.4.</div>
      <div>&#160;</div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">Pre-Clinical Studies</font>&#8221; means <font style="font-style: italic;">in vitro</font> and <font style="font-style: italic;">in vivo</font> studies of a Product,
        not in humans, including those studies conducted in whole animals and other test systems, designed to determine the toxicity, bioavailability, and pharmacokinetics of such Product and whether such Product has a desired effect.</div>
      <div style="text-align: justify;"> <br>
      </div>
      <div id="DSPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
        <div id="DSPFPageNumberArea" style="text-align: center;"><font id="DSPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">75</font></div>
        <div id="DSPFPageBreak" style="page-break-after: always;">
          <hr style="border-width: 0px; clear: both; margin: 4px 0px; width: 100%; height: 2px; color: #000000; background-color: #000000;" noshade="noshade"></div>
        <div style="width: 100%;" id="DSPFPageHeader">Confidential</div>
      </div>
      <div style="text-align: justify;"><a name="z_Ref198615892"></a>&#8220;<font style="font-weight: bold; font-style: italic;">Pre-Licensing Milestone Event</font>&#8221; has the meaning set forth in Section 6.2.</div>
      <div>&#160;</div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">Prior Agreements</font>&#8221; means the Agreements listed on <u>Schedule 8.2.2(e)</u> attached hereto.</div>
      <div>&#160;</div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">Proceeding</font>&#8221; means an action, suit or proceeding.</div>
      <div>&#160;</div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">Product</font>&#8221; means, on a Drug Discovery Program-by-Drug Discovery Program basis, a finished drug product containing a unique and specific Compound as an active
        pharmaceutical ingredient.&#160; Each Product shall contain a different specific Compound (s).</div>
      <div>&#160;</div>
      <div style="text-align: justify;"><a name="z_Ref187070827"></a><a name="z_Ref187073059"></a><a name="z_Ref189191542"></a>&#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 on or after the Effective Date, including any Program Patents, claiming (i) the specific composition of matter of a Product, or (ii) methods of using a Product as a prophylactic or therapeutic; <font style="font-style: italic;">provided however</font>, Patent Rights Controlled by Isis or any of its Affiliates that (y) include claims that are directed to subject matter applicable to ASOs in general, or (z) include an ASO, the sequence of which targets the RNA
        that encodes a Collaboration Target and the RNA of a gene that does not encode a Collaboration Target, will not be considered Product-Specific Patents, and in the case of (y) and (z), such Patent Rights will be considered Isis Core Technology
        Patents.</div>
      <div>&#160;</div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">Program Patents</font>&#8221; has the meaning set forth in Section 7.1.2.</div>
      <div>&#160;</div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">Prosecution and Maintenance</font>&#8221; or &#8220;<font style="font-weight: bold; font-style: italic;">Prosecute and Maintain</font>&#8221; means, with regard to a Patent Right,
        the preparing, filing, prosecuting and maintenance of such Patent Right, as well as handling re-examinations, reissues, and requests for patent term extensions with respect to such Patent Right, together with the conduct of interferences, the
        defense of oppositions and other similar proceedings with respect to the particular Patent Right.&#160; For clarification, &#8220;<font style="font-weight: bold; font-style: italic;">Prosecution and Maintenance</font>&#8221; or &#8220;<font style="font-weight: bold; font-style: italic;">Prosecute and Maintain</font>&#8221; will not include any other enforcement actions taken with respect to a Patent Right.</div>
      <div>&#160;</div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">Receiving Party</font>&#8221; has the meaning set forth in Section 11.1.</div>
      <div>&#160;</div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">Regulatory Approval</font>&#8221; means the approval necessary for the commercial manufacture, distribution, marketing, promotion, offer for sale, use, import, export,
        and sale of a pharmaceutical product in a jurisdiction regulated by a Regulatory Authority.</div>
      <div>&#160;</div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">Regulatory Authority</font>&#8221; means any governmental authority, including the FDA, EMA or Koseisho (<font style="font-style: italic;">i.e.,</font> the Japanese
        Ministry of Health and Welfare, or any successor agency thereto), that has responsibility for granting any licenses or approvals or granting pricing or reimbursement approvals necessary for the marketing and sale of a Product in any country.</div>
      <div>&#160;</div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">Research</font>&#8221; means conducting the research activities with Compounds as set forth in each Drug Discovery Plan, including pre-clinical research and lead
        optimization, <font style="font-style: italic;">but specifically excluding</font> Development and Commercialization.&#160; When used as a verb, &#8220;<font style="font-style: italic;">Researching</font>&#8221; means to engage in Research.</div>
      <div>&#160;</div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">RMC</font>&#8221; means Isis&#8217; Research Management Committee, or any successor committee.</div>
      <div>&#160;</div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">ROFN Period</font>&#8221; has the meaning set forth in <u>Section 2.1.2</u>.</div>
      <div style="text-align: justify;"> <br>
      </div>
      <div id="DSPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
        <div id="DSPFPageNumberArea" style="text-align: center;"><font id="DSPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">76</font></div>
        <div id="DSPFPageBreak" style="page-break-after: always;">
          <hr style="border-width: 0px; clear: both; margin: 4px 0px; width: 100%; height: 2px; color: #000000; background-color: #000000;" noshade="noshade"></div>
        <div style="width: 100%;" id="DSPFPageHeader">Confidential</div>
      </div>
      <div style="text-align: justify;">
        <div>&#8220;<font style="font-weight: bold; font-style: italic;">ROFN Termination Event</font>&#8221; has the meaning set forth in <u>Section 2.1.2</u>.</div>
      </div>
      <div style="text-align: justify;"> <br>
      </div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">Royalty Period</font>&#8221; has the meaning set forth in Section 6.8.2(a).</div>
      <div>&#160;</div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">Sales Milestone Event</font>&#8221; has the meaning provided in <u>Section 6.7</u>.</div>
      <div>&#160;</div>
      <div style="text-align: justify; font-size: 12pt;"><font style="font-weight: bold; font-size: 10pt;">&#8220;</font><font style="font-size: 10pt;">[***].</font></div>
      <div>&#160;</div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">Specific Performance Milestone Event</font>&#8221; has the meaning set forth in <u>Section 5.2</u>.</div>
      <div>&#160;</div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">Step-In Party</font>&#8221; has the meaning set forth in <u>Section 7.4.1</u>.</div>
      <div>&#160;</div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">Sublicensee</font>&#8221; means a Third Party to whom a Party or its Affiliates or Sublicensees has granted a sublicense or license under any Licensed Technology or JBI
        Technology, as the case may be, licensed to such Party in accordance with the terms of this Agreement.</div>
      <div>&#160;</div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">Substitution Fee&#8221;</font><font style="font-style: italic;">&#160;</font>means $[***] per substituted target to be paid by JBI following Isis&#8217; acceptance of JBI&#8217;s
        proposed substitute gene target under <u>Section 1.2.5</u><font style="font-weight: bold;"> .</font></div>
      <div>&#160;</div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">Supplemental Information</font>&#8221; has the meaning provided in <u>Section 1.3.5</u>.</div>
      <div>&#160;</div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">Target Nomination Period</font>&#8221; has the meaning set forth in <u>Section 1.2.1</u>.</div>
      <div>&#160;</div>
      <div style="text-align: justify;">[***] &#8220;<font style="font-weight: bold; font-style: italic;">Third Party</font>&#8221; means a Person or entity other than the Parties or their respective Affiliates.</div>
      <div>&#160;</div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">Third Party Obligations</font>&#8221; means any financial and non-financial encumbrances, obligations, restrictions, or limitations imposed by an agreement between Isis
        and a Third Party (including the Isis In-License Agreements) that relate to a Product, a Collaboration Target, including field or territory restrictions, covenants, milestone payments, diligence obligations, sublicense revenue, royalties, or other
        payments.</div>
      <div>&#160;</div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">United States</font>&#8221; or &#8220;<font style="font-weight: bold; font-style: italic;">U.S.</font>&#8221; means the fifty states of the United States of America and all of its
        territories and possessions and the District of Columbia.</div>
      <div>&#160;</div>
      <div style="text-align: justify;">&#8220;<font style="font-weight: bold; font-style: italic;">Valid Claim</font>&#8221; means a claim (i) of any issued, unexpired United States or foreign Patent Right, which will not, in the country of issuance, have been
        donated to the public, disclaimed, nor held invalid or unenforceable by a court of competent jurisdiction in an unappealed or unappealable decision, or (ii) of any United States or foreign patent application within a Patent Right, which will not,
        in the country in question, have been cancelled, withdrawn, abandoned nor been pending for more than six years, not including in calculating such six-year period time in which such application is in interference or opposition or similar proceedings
        or time in which a decision of an examiner is being appealed.&#160; Notwithstanding the foregoing, on a country-by-country basis, a patent application pending for more than six years will not be considered to have any Valid Claim for purposes of this
        Agreement unless and until a patent meeting the criteria set forth in clause (i) above with respect to such application issues.</div>
      <div>&#160;</div>
      <div id="DSPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
        <div id="DSPFPageNumberArea" style="text-align: center;"><font id="DSPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">77</font></div>
        <div id="DSPFPageBreak" 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 style="width: 100%;" id="DSPFPageHeader">Confidential</div>
      </div>
      <div style="text-align: center; font-variant: small-caps; font-weight: bold;"><u>Appendix 2</u></div>
      <div>&#160;</div>
      <div style="text-align: center; font-variant: small-caps; font-weight: bold;"><u>Development Candidate Checklist</u></div>
      <div>&#160;</div>
      <div style="text-align: center;"><img src="image13.jpg"><br>
        <br>
      </div>
      <div>&#160;</div>
      <div id="DSPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
        <div id="DSPFPageNumberArea" style="text-align: center;"><font id="DSPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">78</font></div>
        <div id="DSPFPageBreak" 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 style="width: 100%;" id="DSPFPageHeader">Confidential</div>
      </div>
      <div style="text-align: center; font-variant: small-caps; font-weight: bold;"><u>Appendix 3</u></div>
      <div>&#160;</div>
      <div style="text-align: center; font-weight: bold;">J&amp;J Universal Calendar</div>
      <div>&#160;</div>
      <div style="text-align: center;"><img src="image11.jpg" height="779" width="458"></div>
      <div>&#160;</div>
      <div id="DSPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
        <div id="DSPFPageNumberArea" style="text-align: center;"><font id="DSPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">79</font></div>
        <div id="DSPFPageBreak" 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 style="width: 100%;" id="DSPFPageHeader">Confidential</div>
      </div>
      <div style="text-align: center; font-variant: small-caps; font-weight: bold;"><u>Schedule 1.6.1</u></div>
      <div>&#160;</div>
      <div style="text-align: center; font-variant: small-caps; font-weight: bold;"><u>JRC Governance</u></div>
      <div>&#160;</div>
      <table id="zf5a8f6bc7814492b9c15abaddc4ac442" class="DSPFListTable" style="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;">(a)</td>
            <td style="width: auto; vertical-align: top;">
              <div>The JRC will determine the JRC operating procedures, including frequency of meetings (at least quarterly), location of meetings, and responsibilities for agendas and minutes.&#160; The JRC will codify these operating procedures in the written
                minutes of the first meeting.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table id="za014d8a628194e729cbb4b9cd049a0c5" class="DSPFListTable" style="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;">(b)</td>
            <td style="width: auto; vertical-align: top;">
              <div>The JRC may hold meetings in person or by audio or video conference as determined by the JRC; but at least two meetings per year will be in person (one held at Isis&#8217; facilities, and the other held at JBI&#8217;s facilities in the U.S.).&#160;
                Alliance Managers will attend JRC meetings as participating non-members.&#160; In addition, upon prior approval of the other Party, each Party may invite its employees or consultants to attend JRC meetings, including any subject matter expert(s)
                with valuable knowledge of Collaboration Targets or the diseases associated with such Collaboration Targets.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table id="z19d56ef60e854adc8f0ccbd107809222" class="DSPFListTable" style="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;">(c)</td>
            <td style="width: auto; vertical-align: top;">
              <div>The co-chairs will be responsible for ensuring that activities occur as set forth in this Agreement, including ensuring that JRC meetings occur, JRC recommendations are properly reflected in the minutes, and any dispute is given prompt
                attention and resolved in accordance with <u>Section 1.6.3</u>, <u>Section 7.1.3</u> and <u>Section 12.1</u>, as applicable.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table id="z38068d2219cf4ebf9f02d11afaf84dc9" class="DSPFListTable" style="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;">(d)</td>
            <td style="width: auto; vertical-align: top;">
              <div>The JRC members from the same Party will collectively have one vote.&#160; The JRC will strive to make recommendations with approval of both Isis members and JBI members, and record such recommendations in the minutes of the applicable JRC
                meeting.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table id="zb8b260fbd7554da49798ff866a5ca8f7" class="DSPFListTable" style="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;">(e)</td>
            <td style="width: auto; vertical-align: top;">
              <div>The JRC may form subcommittees and working groups as it determines in order to carry out its activities under this Agreement, all of which will dissolve when the JRC dissolves.</div>
            </td>
          </tr>

      </table>
      <div> <br>
      </div>
      <div id="DSPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
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      <div style="text-align: center; font-variant: small-caps; font-weight: bold;"><u>Schedule 1.6.5</u></div>
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          <tr>
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              <div>Developing a mutually agreed alliance launch plan covering any activities and systems that the Parties need to implement within the first 100 days after the Effective Date to support the Drug Discovery Programs;</div>
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              <div>Organizing JRC meetings, including agendas, drafting minutes, and publishing final minutes;</div>
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              <div>Supporting the co-chairs of the JRC with organization of meetings, information exchange, meeting minutes, and facilitating dispute resolution as necessary;</div>
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      <div>&#160;</div>
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          <tr>
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              <div>Preparing status and progress reports on the above as determined necessary by the JRC;</div>
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      <div>&#160;</div>
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          <tr>
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              <div>Ensuring compliance in maintaining the Isis Internal ASO Safety Database as outlined in <u>Section 5.6</u>;</div>
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      <div>&#160;</div>
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              <div>Ensuring proper approval of publications prior to submission as required in <u>Section 11.4</u>; and</div>
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          </tr>

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      <div>&#160;</div>
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              <div>Understanding and communicating the components contained in the relationship-management document provided by Isis to JBI, to assist JBI in understanding and complying with the contractual obligations under the Isis In-License Agreements
                after Option exercise.</div>
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      <div> <br>
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      <div>&#160;</div>
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      <div style="text-align: center;">[<font style="font-weight: bold;">***</font>]</div>
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        <div style="width: 100%;" id="DSPFPageHeader">Confidential</div>
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      <div style="text-align: center; font-variant: small-caps; font-weight: bold;"><u>Schedule 5.2</u></div>
      <div>&#160;</div>
      <div style="text-align: center; font-weight: bold;">JBI&#8217;s Development and Commercialization Activities</div>
      <div>&#160;</div>
      <div style="text-align: center;">[<font style="font-style: italic;">***</font><u>]</u></div>
      <div>&#160;</div>
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        <div id="DSPFPageNumberArea" style="text-align: center;"><font id="DSPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">83</font></div>
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        <div style="width: 100%;" id="DSPFPageHeader">Confidential</div>
      </div>
      <div style="text-align: center; font-variant: small-caps; font-weight: bold;"><u>Schedule 6.9.1</u></div>
      <div>&#160;</div>
      <div style="text-align: center; font-weight: bold;">Certain Isis In-License Agreements</div>
      <div>&#160;</div>
      <div style="text-align: center; font-weight: bold;">(Relevant to the Drug Discovery Programs as of the Effective Date)</div>
      <div>&#160;</div>
      <div style="text-align: center;">[***]</div>
      <div>&#160;</div>
      <div id="DSPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
        <div id="DSPFPageNumberArea" style="text-align: center;"><font id="DSPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">84</font></div>
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        <div style="width: 100%;" id="DSPFPageHeader">Confidential</div>
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      <div style="text-align: center; font-size: 12pt; font-weight: bold;"><font style="font-variant: small-caps; font-size: 10pt;"><u>Schedule 8.2.2(</u></font><font style="font-size: 10pt;"><u>a</u><font style="font-variant: small-caps;"><u>)</u></font></font></div>
      <div>&#160;</div>
      <div style="text-align: center; font-weight: bold;">Isis Core Technology Patents</div>
      <div>&#160;</div>
      <div style="text-align: center; font-weight: bold;">[***]</div>
      <div>&#160;</div>
      <div id="DSPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
        <div id="DSPFPageNumberArea" style="text-align: center;"><font id="DSPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">85</font></div>
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      <div style="text-align: center; font-size: 12pt; font-weight: bold;"><font style="font-variant: small-caps; font-size: 10pt;"><u>Schedule 8.2.2(</u></font><font style="font-size: 10pt;"><u>b</u><font style="font-variant: small-caps;"><u>)</u></font></font></div>
      <div>&#160;</div>
      <div style="text-align: center; font-weight: bold;">Isis Manufacturing and Analytical Patents</div>
      <div>&#160;</div>
      <div style="text-align: center; font-weight: bold;">[***]</div>
      <div>&#160;</div>
      <div id="DSPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
        <div id="DSPFPageNumberArea" style="text-align: center;"><font id="DSPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">86</font></div>
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        <div style="width: 100%;" id="DSPFPageHeader">Confidential</div>
      </div>
      <div style="text-align: center; font-size: 12pt; font-weight: bold;"><font style="font-variant: small-caps; font-size: 10pt;"><u>Schedule 8.2.2(</u></font><font style="font-size: 10pt;"><u>c</u><font style="font-variant: small-caps;"><u>)</u></font></font></div>
      <div>&#160;</div>
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      <div>&#160;</div>
      <div style="text-align: center;">[<font style="font-weight: bold;">***</font>]</div>
      <div>&#160;</div>
      <div id="DSPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
        <div id="DSPFPageNumberArea" style="text-align: center;"><font id="DSPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">87</font></div>
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        <div style="width: 100%;" id="DSPFPageHeader">Confidential</div>
      </div>
      <div style="text-align: center; font-size: 12pt; font-weight: bold;"><font style="font-variant: small-caps; font-size: 10pt;"><u>Schedule 8.2.2(</u></font><font style="font-size: 10pt;"><u>d</u><font style="font-variant: small-caps;"><u>)</u></font></font></div>
      <div>&#160;</div>
      <div style="text-align: center; font-weight: bold;">Isis Formulation Patents</div>
      <div>&#160;</div>
      <div style="text-align: center; font-weight: bold;">[***]</div>
      <div>&#160;</div>
      <div id="DSPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
        <div id="DSPFPageNumberArea" style="text-align: center;"><font id="DSPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">88</font></div>
        <div id="DSPFPageBreak" style="page-break-after:always;">
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      <div style="text-align: center; font-variant: small-caps; font-weight: bold;"><u>Schedule 8.2.2(e)</u></div>
      <div>&#160;</div>
      <div style="text-align: center; font-weight: bold;">Prior Agreements</div>
      <div><br>
      </div>
      <div style="text-align: center;">[***]</div>
      <div> <br>
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        <div id="DSPFPageNumberArea" style="text-align: center;"><font id="DSPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">89</font></div>
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        <div style="width: 100%;" id="DSPFPageHeader">Confidential</div>
      </div>
      <div style="text-align: center;">Schedule 11.4 &#8211; Press Release</div>
      <div>&#160;</div>
      <div style="text-align: center; font-weight: bold;">&#160;ISIS PHARMACEUTICALS ANNOUNCES COLLABORATION WITH JANSSEN TO DISCOVER AND DEVELOP RNA-TARGETED THERAPEUTICS FOR AUTOIMMUNE DISEASES IN THE GI TRACT</div>
      <div><br>
      </div>
      <div style="text-align: center; font-style: italic;">-- Collaboration Combines Isis&#8217; RNA-Targeted Technology with Expertise of Janssen in Autoimmune Disorders and Therapeutic Formulation --</div>
      <div><br>
      </div>
      <div>Carlsbad, Calif., Jan. [5], 2015 &#8211;Isis Pharmaceuticals, Inc. (NASDAQ: ISIS) today announced that the company has&#160; entered into a global collaboration with Janssen Biotech, Inc. (Janssen) to discover and develop antisense drugs to treat
        autoimmune disorders of the gastrointestinal (GI) tract.&#160; The collaboration brings together Isis&#8217; RNA-targeted technology platform and the expertise of Janssen in autoimmune disorders and therapeutic formulation to discover and develop antisense
        drugs that can be locally administered, including oral delivery, to treat autoimmune disorders in the GI tract.</div>
      <div><br>
      </div>
      <div>&#8220;We are excited to be working with Janssen to apply our drug discovery and development efforts in this therapeutic area.&#160; This collaboration broadens the utility of our drug discovery technology to new targets in the GI tract and expands the
        administration of antisense drugs to local delivery, including oral delivery, to the gut,&#8221; said B. Lynne Parshall, chief operating officer at Isis Pharmaceuticals. &#8220;We are the leader in RNA-targeted therapeutics and our innovation and the successes
        of our pipeline drugs enable us to form collaborations, like this one, with leaders in specific therapeutic areas.&#160; This partnering strategy ensures that we have access to resources that support and enhance our drug discovery efforts and also
        provides us with collaborators, like Janssen, who are uniquely capable of conducting development, marketing and commercial efforts for these drugs.&#160; .&#8221;</div>
      <div><br>
      </div>
      <div>Under the terms of the agreement, which covers three programs, Isis will receive $35 million in upfront payments, including a payment to initiate human&#160; lead optimization on the first collaboration target.&#160; Isis is eligible to receive nearly
        $800 million in development, regulatory and sales milestone payments and license fees for these programs.&#160; In addition, Isis will receive tiered royalties that on average are double-digits on sales from any product that is successfully
        commercialized.&#160; Janssen has the option to license a drug from each of the programs once a development candidate is identified. If Janssen exercises its option, it will assume global development, regulatory and commercialization responsibilities.</div>
      <div><br>
      </div>
      <div style="color: rgb(0, 0, 0); font-weight: bold;">ABOUT ISIS PHARMACEUTICALS, INC.</div>
      <div>Isis is exploiting its leadership position in RNA-targeted technology to discover and develop novel drugs for its product pipeline and for its partners.&#160; Isis&#8217; broad pipeline consists of 34 drugs to treat a wide variety of diseases with an
        emphasis on cardiovascular, metabolic, severe and rare diseases, including neurological disorders, and cancer.&#160; Isis&#8217; partner, Genzyme, is commercializing Isis&#8217; lead product, KYNAMRO<sup style="vertical-align: text-top; line-height: 1; font-size: smaller;">&#174;</sup>, in the United States and other countries for the treatment of patients with homozygous FH.&#160; Isis has numerous drugs in Phase 3 development in severe and rare and cardiovascular diseases.&#160; These include a ISIS-APOCIII<sub style="vertical-align: bottom; line-height: 1; font-size: smaller;">Rx</sub>, a drug Isis is developing to treat patients with severely high triglycerides, such as patients with familial chylomicronemia syndrome; ISIS-TTR<sub style="vertical-align: bottom; line-height: 1; font-size: smaller;">Rx</sub>, a drug Isis is developing with GSK to treat patients with the polyneuropathy form of TTR amyloidosis; and, ISIS-SMN<sub style="vertical-align: bottom; line-height: 1; font-size: smaller;">Rx</sub>, a drug Isis is developing with Biogen Idec to treat infants and children with spinal muscular atrophy, a severe and rare neuromuscular disease.&#160; Isis&#8217; patents provide strong and extensive protection for its drugs
        and technology.&#160; Additional information about Isis is available at www.isispharm.com.</div>
      <div> <br>
      </div>
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      <div style="color: rgb(0, 0, 0); font-weight: bold;">ISIS PHARMACEUTICALS&#8217; FORWARD-LOOKING STATEMENT</div>
      <div>This press release includes forward-looking statements regarding Isis&#8217; alliance with Janssen, Isis&#8217; research, development and commercial opportunities in developing antisense drugs to treat inflammatory bowel disease.&#160; Any statement describing
        Isis&#8217; goals, expectations, financial or other projections, intentions or beliefs is a forward-looking statement and should be considered an at-risk statement.&#160; Such statements are subject to certain risks and uncertainties, particularly those
        inherent in the process of discovering, developing and commercializing drugs that are safe and effective for use as human therapeutics, and in the endeavor of building a business around such drugs.&#160; Isis&#8217; forward-looking statements also involve
        assumptions that, if they never materialize or prove correct, could cause its results to differ materially from those expressed or implied by such forward-looking statements.&#160; Although Isis&#8217; forward-looking statements reflect the good faith
        judgment of its management, these statements are based only on facts and factors currently known by Isis.&#160; As a result, you are cautioned not to rely on these forward-looking statements.&#160; These and other risks concerning Isis&#8217; programs are
        described in additional detail in Isis&#8217; annual report on Form 10-K for the year ended December 31, 2013, and its most recent quarterly report on Form 10-Q, which are on file with the SEC. Copies of these and other documents are available from the
        Company.</div>
      <div><br>
      </div>
      <div>In this press release, unless the context requires otherwise, &#8220;Isis,&#8221; &#8220;Company,&#8221; &#8220;we,&#8221; &#8220;our,&#8221; and &#8220;us&#8221; refers to Isis Pharmaceuticals and its subsidiaries.</div>
      <div><br>
      </div>
      <div>Isis Pharmaceuticals<sup style="vertical-align: text-top; line-height: 1; font-size: smaller;">&#174;</sup> is a registered trademark of Isis Pharmaceuticals, Inc.&#160; KYNAMRO<sup style="vertical-align: text-top; line-height: 1; font-size: smaller;">&#174;</sup>
        is a registered trademark of Genzyme Corporation.</div>
      <div><br>
      </div>
      <div style="font-weight: bold;">Isis Pharmaceuticals&#8217; Contacts:</div>
      <div style="font-weight: bold;"> <br>
      </div>
      <table id="z867e3d22f926485b9c6834f7aafc8b80" 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;">
              <div style="text-align: justify;">D. Wade Walke, Ph.D.</div>
              <div style="text-align: justify;">Vice President, Corporate Communications and Investor Relations</div>
              <div style="text-align: justify;">760-603-2741</div>
            </td>
            <td style="width: 50%; vertical-align: top;">
              <div style="text-align: justify;">Amy Blackley, Ph.D.</div>
              <div style="text-align: justify;">Associate Director, Corporate Communications</div>
              <div style="text-align: justify;">760-603-2772</div>
            </td>
          </tr>

      </table>
      <div> <br>
      </div>
      <div style="text-align: center;">###</div>
      <div> <br>
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<DOCUMENT>
<TYPE>EX-10.56
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<FILENAME>exhibit10_56.htm
<DESCRIPTION>EXHIBIT 56
<TEXT>
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          <td style="width: 50%; vertical-align: top;">&#160;</td>
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    <div>&#160;</div>
    <div style="font-weight: bold;">CERTAIN IDENTIFIED INFORMATION HAS BEEN EXCLUDED FROM THE EXHIBIT BECAUSE IT IS BOTH (I) NOT MATERIAL AND (II) WOULD BE COMPETITIVELY HARMFUL IF PUBLICLY DISCLOSED.&#160; SUCH EXCLUDED INFORMATION HAS BEEN MARKED WITH &#8220;<a name="z_Hlk63751537"></a>[***]&#8221;.</div>
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    <div style="text-align: right; font-weight: bold;"><u>Exhibit 10.56</u></div>
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    <div style="text-align: center;">December 21, 2016</div>
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        <tr>
          <td style="width: 60%; vertical-align: top;">
            <div style="text-align: justify;">Ionis Pharmaceuticals, Inc.</div>
          </td>
          <td style="width: 40%; vertical-align: top;">
            <div style="text-align: justify;">Ionis Pharmaceuticals, Inc.</div>
          </td>
        </tr>
        <tr>
          <td style="width: 60%; vertical-align: top;">
            <div style="text-align: justify;">2855 Gazelle Court</div>
          </td>
          <td style="width: 40%; vertical-align: top;">
            <div style="text-align: justify;">2855 Gazelle Court</div>
          </td>
        </tr>
        <tr>
          <td style="width: 60%; vertical-align: top;">
            <div style="text-align: justify;">Carlsbad, CA 92010</div>
          </td>
          <td style="width: 40%; vertical-align: top;">
            <div style="text-align: justify;">Carlsbad, CA 92010</div>
          </td>
        </tr>
        <tr>
          <td style="width: 60%; vertical-align: top;">
            <div style="text-align: justify;">Attention: Chief Operating Officer</div>
          </td>
          <td style="width: 40%; vertical-align: top;">
            <div style="text-align: justify;">Attention: General Counsel</div>
          </td>
        </tr>

    </table>
    <div><br>
    </div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-style: italic;">Re:</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-style: italic;"><u>First Amendment To Research Collaboration, Option and License Agreement of December 22, 2014</u></div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <div style="text-align: justify;">Dear Madame or Sir:</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt;">Reference is made to the Research Collaboration, Option and License Agreement of December 22, 2014 (the &#8220;<font style="font-weight: bold; font-style: italic;">Agreement</font>&#8221;),<font style="font-weight: bold;">&#160;</font>by<font style="font-weight: bold;">&#160;</font>and between Janssen Biotech Inc. (&#8220;<font style="font-weight: bold; font-style: italic;">JBI</font>&#8221;), and Ionis Pharmaceuticals, Inc. (formerly Isis Pharmaceuticals,
      Inc.; hereinafter &#8220;<font style="font-weight: bold; font-style: italic;">Ionis</font>&#8221;), or individually as &#8220;<font style="font-weight: bold; font-style: italic;">Party</font>&#8221; or collectively as &#8220;<font style="font-weight: bold; font-style: italic;">Parties</font>.&#8221;

      This document is a &#8220;<font style="font-weight: bold; font-style: italic;">First Amendment</font>&#8221; to the Agreement and the &#8220;<font style="font-weight: bold; font-style: italic;">First Amendment Effective Date</font>&#8221; shall be the date of the last
      signature below.</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt;">In general, the Parties agreed to modify the Agreement to reflect alignment on the terms and conditions which will enable JBI to propose, and for Ionis to accept, a third target (<font style="font-weight: bold;">[***]</font>), and for JBI to Develop and Commercialize an <font style="font-weight: bold;">[***]</font> Compound that JBI selects as the JBI <font style="font-weight: bold;">[***]</font> Development Candidate. This
      First Amendment includes changes to the companion financials and describes the consideration associated with entering into this First Amendment.</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt;">To effectuate the agreed upon changes, the Parties agree to the provisions described herein.</div>
    <div>&#160;</div>
    <div style="text-align: justify; font-size: 12pt;"><font style="font-size: 10pt; font-weight: bold; font-style: italic;"><u>Definitions</u></font><font style="font-size: 10pt; font-weight: bold; font-style: italic;">.&#160; </font><font style="font-size: 10pt;">The Parties agree to introduce new definitions to the Agreement as follows:</font></div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt;">&#8220;<font style="font-weight: bold; font-style: italic;">GLP Toxicology Study</font>&#8221; means a GLP toxicology study necessary to meet the requirements for filing an IND.</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt;">&#8220;<font style="font-weight: bold; font-style: italic;">Ionis </font><font style="font-weight: bold;">[***]</font><font style="font-weight: bold; font-style: italic;"> Field</font>&#8221; means any
      prophylactic, therapeutic or other use or form of administration of any ASO that is designed to bind to the RNA that encodes <font style="font-weight: bold;">[***]</font> for any indication other than treatment of a disease of the gastrointestinal
      tract.</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt;">&#8220;<font style="font-weight: bold;">[***]</font>&#8221; means the gene, <font style="font-weight: bold;">[***]</font>.</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt;">&#8220;<a name="z_Hlk63751581"></a><font style="font-weight: bold;">[***]</font><font style="font-weight: bold; font-style: italic;"> Compound</font>&#8221; means any ASO that is designed to bind to the RNA that
      encodes <font style="font-weight: bold;">[***]</font>, where such ASO is discovered by Ionis prior to <font style="font-weight: bold;">[***]</font>, including <font style="font-weight: bold;">[***]</font>.</div>
    <div>&#160;</div>
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                <div>
                  <div style="text-align: left;">December 21, 2016</div>
                </div>
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              <td style="width: 50.00%;">
                <div>&#160;</div>
              </td>
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            <tr>
              <td style="width: 50.00%;">
                <div>&#160;First Amendment</div>
              </td>
              <td style="width: 50.00%;">
                <div>&#160;</div>
              </td>
            </tr>
            <tr>
              <td style="width: 50.00%;">
                <div>&#160;Page&#160;<font id="DSPFPageNumber">2</font> of&#160; 5<br>
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        </table>
      </div>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"> </div>
    <div style="text-align: justify; text-indent: 36pt;">&#8220;<font style="font-weight: bold; font-style: italic;">IONIS-</font><font style="font-weight: bold;">[***]</font><sub style="font-style: italic; font-weight: bold; vertical-align: bottom; line-height: 1; font-size: smaller;">Rx</sub>&#8221; means the compound known as <font style="font-weight: bold;">[***]</font>.</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt;">&#8220;<font style="font-weight: bold; font-style: italic;">JBI </font><font style="font-weight: bold;">[***]</font><font style="font-weight: bold; font-style: italic;"> Development Candidate</font>&#8221;
      means the <font style="font-weight: bold;">[***]</font> Compound selected by JBI. Such JBI <font style="font-weight: bold;">[***]</font> Development Candidate will be a &#8220;<font style="font-style: italic;">Product</font>&#8221; under the Agreement.</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt;">&#8220;<font style="font-weight: bold; font-style: italic;">JBI </font><font style="font-weight: bold;">[***]</font><font style="font-weight: bold; font-style: italic;"> Field</font>&#8221; means <font style="font-weight: bold;">[***]</font> delivery of the JBI <font style="font-weight: bold;">[***]</font> Development Candidate for treatment of diseases of the gastrointestinal tract, <font style="font-style: italic;"><u>unless</u></font>
      expanded to include the Expanded GI Field.</div>
    <div>&#160;</div>
    <div style="text-align: justify;">Defined terms used but not defined herein have the meaning ascribed to such terms in the Agreement.</div>
    <div>&#160;</div>
    <div style="text-align: justify; font-style: italic; font-weight: bold;"><u>Agreement Provisions</u></div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt; font-size: 12pt;"><font style="font-size: 10pt; font-weight: bold;"><u>Confirmation - Section 1.2.3</u></font><font style="font-size: 10pt;"> &#8211; JBI proposed a third gene target designated <font style="font-weight: bold;">[***]</font> and Ionis accepts this designation.</font></div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt; font-size: 12pt;"><font style="font-size: 10pt; font-weight: bold;"><u>Confirmation - Section 1.2.4</u></font><font style="font-size: 10pt;"> &#8211; <font style="font-weight: bold;">[***]</font> is now a
        Collaboration Target.</font></div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt; font-size: 12pt;"><font style="font-size: 10pt; font-weight: bold;"><u>Amendment of Section 2.1.3</u></font><font style="font-size: 10pt;"> &#8211; <u>Section 2.1.3</u> of the Agreement is amended to
        include a new item (e) as follows:</font></div>
    <div>&#160;</div>
    <div style="text-align: justify; margin-right: 36pt; margin-left: 36pt;">&#8220;(e) The research, development, manufacture, commercialization or other exploitation of IONIS-<font style="font-weight: bold;">[***]</font><sub style="vertical-align: bottom; line-height: 1; font-size: smaller;">Rx</sub> or any other ASO that is designed to bind to the RNA that encodes <font style="font-weight: bold;">[***]</font>, in each case by Ionis independently or for or with any of its Affiliates or any Third
      Party (including the grant of any license to any Third Party), in each case in the Ionis <font style="font-weight: bold;">[***]</font> Field.&#8221;</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt; font-size: 12pt;"><font style="font-size: 10pt; font-weight: bold;"><u>Amendment of Section 4.1.1 Solely with respect to the JBI </u></font><font style="font-size: 10pt; font-weight: bold;"><u>[***]</u></font><font style="font-size: 10pt; font-weight: bold;"><u> Development Candidate</u></font><font style="font-size: 10pt;"> &#8211; The Parties agree that, solely with respect to the JBI <font style="font-weight: bold;">[***]</font> Development Candidate, <u>Section

          4.1.1</u> of the Agreement is deleted in its entirety and replaced with the following language:</font></div>
    <div>&#160;</div>
    <div style="text-align: justify; margin-right: 36pt; margin-left: 36pt;">&#8220;<font style="font-weight: bold;">4.1.1</font>&#160; <font style="font-weight: bold;"><u>Development and Commercialization License</u></font>. Subject to the terms and conditions of
      this Agreement, effective upon JBI&#8217;s exercise of the Option for the JBI <font style="font-weight: bold;">[***]</font> Development Candidate in accordance with this Agreement, Ionis grants to JBI (i) a worldwide, exclusive, royalty-bearing,
      sublicensable (in accordance with <u>Section 4.1.2</u> below) license under the Isis Product Specific Patents to Research, Develop, Manufacture, have Manufactured (in accordance with <u>Section 4.1.2</u> below), register, market and Commercialize
      the JBI <font style="font-weight: bold;">[***]</font> Development Candidate in the JBI <font style="font-weight: bold;">[***]</font> Field, and (ii) a worldwide, exclusive, royalty-bearing, sublicensable (in accordance with <u>Section 4.1.2</u>
      below) license under the Licensed Technology other than the Isis Product Specific Patents to Research, Develop, Manufacture, have Manufactured (in accordance with <u>Section 4.1.2</u> below), register, market and Commercialize the JBI <font style="font-weight: bold;">[***]</font> Development Candidate in the JBI <font style="font-weight: bold;">[***]</font> Field. The grants described under subsection (i) and subsection (ii) in no way limit Ionis&#8217; ability to grant additional licenses
      to Third Parties under the Licensed Technology in the Ionis <font style="font-weight: bold;">[***]</font> Field.&#8221;</div>
    <div>&#160;</div>
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                <div>
                  <div style="text-align: left;">December 21, 2016</div>
                </div>
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              <td style="width: 50.00%;">
                <div>&#160;</div>
              </td>
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            <tr>
              <td style="width: 50.00%;">
                <div>&#160;First Amendment</div>
              </td>
              <td style="width: 50.00%;">
                <div>&#160;</div>
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        </table>
      </div>
    </div>
    <div style="text-align: justify; text-indent: 36pt; font-size: 12pt;"><font style="font-size: 10pt; font-weight: bold;"><u>Addition of New Section 4.1.6</u></font><font style="font-size: 10pt; font-weight: bold;"> &#8211; </font><font style="font-size: 10pt; font-weight: bold;">[***]</font><font style="font-size: 10pt; font-weight: bold;"> Administration of JBI </font><font style="font-size: 10pt; font-weight: bold;">[***]</font><font style="font-size: 10pt; font-weight: bold;"> Development
        Candidate</font><font style="font-size: 10pt;">. The Parties acknowledge that the JBI <font style="font-weight: bold;">[***]</font> Field is initially limited to <font style="font-weight: bold;">[***]</font> delivery of the JBI <font style="font-weight: bold;">[***]</font> Development Candidate for treatment of diseases of the gastrointestinal tract. Following JBI&#8217;s exercise of its Option for the JBI <font style="font-weight: bold;">[***]</font> Development Candidate but
        prior to <font style="font-weight: bold;">[***<font style="background-color: rgb(255, 255, 255);">]</font></font><font style="background-color: rgb(255, 255, 255);">&#160;</font><font style="font-weight: bold;"><font style="background-color: rgb(255, 255, 255);">[*</font>**] </font>with the JBI <font style="font-weight: bold;">[***]</font> Development Candidate, JBI may elect to expand the JBI <font style="font-weight: bold;">[***]</font> Field to include the <font style="font-weight: bold;">[***]</font> delivery of the JBI <font style="font-weight: bold;">[***]</font> Development Candidate for the treatment of diseases of the gastrointestinal tract (&#8220;<font style="font-weight: bold; font-style: italic;">Expanded GI Field</font>&#8221;)

        by providing the JRC written notice of such <font style="font-weight: bold;">[***]</font> election. Within <font style="font-weight: bold;">[***]</font> days after timely providing such election notice to the JRC:</font></div>
    <div>&#160;</div>
    <table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zdeda9144519d45fbbfc8138855cdf95f" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 54pt;"><br>
          </td>
          <td style="width: 18pt; vertical-align: top; font-weight: bold;">a)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>In the case where JBI selected IONIS-<font style="font-weight: bold;">[***]</font><sub style="vertical-align: bottom; line-height: 1; font-size: smaller;">Rx</sub> as the JBI <font style="font-weight: bold;">[***]</font> Development
              Candidate and, as of the date the JRC receives such election notice, Ionis has <font style="font-weight: bold;">[***]</font>, then JBI&#8217;s rights under this <u>Section 4.1.6</u> shall be limited to a right to negotiate with Ionis in good
              faith regarding both (i) <font style="font-weight: bold;">[***]</font> and (ii) <font style="font-weight: bold;">[***]</font>; or</div>
          </td>
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    </table>
    <div>&#160;</div>
    <table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z16d4ef3eb8b042df860a0711fe971de3" cellpadding="0" cellspacing="0">

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          <td style="width: 54pt;"><br>
          </td>
          <td style="width: 18pt; vertical-align: top; font-weight: bold;">b)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>In the case where (x) JBI selected IONIS-<font style="font-weight: bold;">[***]</font><sub style="vertical-align: bottom; line-height: 1; font-size: smaller;">Rx</sub> as the JBI <font style="font-weight: bold;">[***]</font> Development
              Candidate but, as of the date the JRC receives such election notice, Ionis <font style="font-style: italic;"><u>has not</u></font>&#160;<font style="font-weight: bold;">[***]</font>, or (y) JBI did not select IONIS-<font style="font-weight: bold;">[***]</font><sub style="vertical-align: bottom; line-height: 1; font-size: smaller;">Rx</sub> as the JBI <font style="font-weight: bold;">[***]</font> Development Candidate, the Parties shall negotiate in good faith both (i) <font style="font-weight: bold;">[***]</font>.</div>
          </td>
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    </table>
    <div>&#160;</div>
    <div style="text-align: justify;">The JBI <font style="font-weight: bold;">[***]</font> Field will only be expanded to include the Expanded GI Field if the Parties mutually agree on the <font style="font-weight: bold;">[***] </font>described in
      subsection (a) or (b) in this <u>Section 4.1.6</u> (as applicable). If JBI progresses a JBI <font style="font-weight: bold;">[***]</font> Development Candidate in the Expanded GI Field all other provisions of the Agreement shall apply to the
      Expanded GI Field and Net Sales from <font style="font-weight: bold;">[***] </font>delivered and a <font style="font-weight: bold;">[***]</font> delivered JBI <font style="font-weight: bold;">[***]</font> Development Candidate will be aggregated
      when calculating payments due under the Agreement royalty tiers.</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt; font-size: 12pt;"><font style="font-size: 10pt; font-weight: bold;"><u>Addition of New Section 5.7</u></font><font style="font-size: 10pt; font-weight: bold;"> - Development and Commercialization
        Cooperation.</font><font style="font-size: 10pt;"> If JBI selects IONIS-<font style="font-weight: bold;">[***]</font><sub style="vertical-align: bottom; line-height: 1; font-size: smaller;">Rx</sub> as the JBI <font style="font-weight: bold;">[***]</font>
        Development Candidate, then within <font style="font-weight: bold;">[***]</font> (<font style="font-weight: bold;">[***]</font>) months after JBI exercises its Option, the Parties will convene to negotiate commercially reasonable terms for
        managing the continued Development and Commercialization of IONIS-<font style="font-weight: bold;">[***]</font><sub style="vertical-align: bottom; line-height: 1; font-size: smaller;">Rx</sub> by both Parties, including procedures for the mutual
        exchange of <font style="font-weight: bold;">[***] </font>and <font style="font-weight: bold;">[***]</font> information associated with IONIS-<font style="font-weight: bold;">[***]</font><sub style="vertical-align: bottom; line-height: 1; font-size: smaller;">Rx</sub>.</font></div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt; font-size: 12pt;"><font style="font-size: 10pt; font-weight: bold;"><u>Addition of New Section 5.8 &#8211; Back-Up JBI </u></font><font style="font-size: 10pt; font-weight: bold;"><u>[***]</u></font><font style="font-size: 10pt; font-weight: bold;"><u> Development Candidate</u></font><font style="font-size: 10pt;">. If JBI has exercised its Option for the JBI <font style="font-weight: bold;">[***]</font> Development Candidate and subsequently
        delivers written notice to Ionis that JBI will discontinue Development of such JBI <font style="font-weight: bold;">[***]</font> Development Candidate for reasons of <font style="font-weight: bold;">[***]</font> (<u>e.g.</u>, <font style="font-weight: bold;">[***]</font> or <font style="font-weight: bold;">[***]</font> issues), then, upon JBI&#8217;s written request to Ionis, JBI may select as a replacement of such JBI <font style="font-weight: bold;">[***]</font> Development
        Candidate any other <font style="font-weight: bold;">[***]</font> Compound (&#8220;<font style="font-weight: bold; font-style: italic;">Back-Up </font><font style="font-weight: bold;">[***]</font><font style="font-weight: bold; font-style: italic;">
          Development Candidate</font>&#8221;) that is not being developed or commercialized (<u>i.e.</u>, such <font style="font-weight: bold;">[***]</font> Compound has at least started a <font style="font-weight: bold;">[***]</font>) by Ionis, its
        Affiliates or its sublicensee as of the date Ionis receives such request from JBI. JBI will select any such Back-Up <font style="font-weight: bold;">[***]</font> Development Candidate within <font style="font-weight: bold;">[***]</font> days
        following the date Ionis receives the discontinuation notice and, unless mutually agreed by Ionis, JBI will be <font style="font-weight: bold;">[***]</font>. Upon any such selection of a Back-Up <font style="font-weight: bold;">[***]</font>
        Development Candidate, such Back-Up <font style="font-weight: bold;">[***]</font> Development Candidate will become the &#8220;<font style="font-style: italic;">JBI </font><font style="font-weight: bold;">[***] </font><font style="font-style: italic;">Development

          Candidate</font>&#8221; and a &#8220;<font style="font-style: italic;">Product</font>&#8221; under and subject to the terms of the Agreement.</font></div>
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                  <div style="text-align: left;">December 21, 2016</div>
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                <div>&#160;</div>
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              <td style="width: 50.00%;">
                <div>&#160;First Amendment</div>
              </td>
              <td style="width: 50.00%;">
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    <div style="text-align: justify; font-style: italic; font-weight: bold;"><u>Financial Provisions</u></div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt; font-size: 12pt;"><font style="font-size: 10pt; font-weight: bold;"><u>Pre-Licensing Milestone Event Payment</u></font><font style="font-size: 10pt;">. To compensate Ionis for the Pre-Licensing
        Milestone Event described in <u>Section 6.3</u>, JBI shall pay $5,000,000 to Ionis within forty-five (45) days following the First Amendment Effective Date.</font></div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt; font-size: 12pt;"><font style="font-size: 10pt; font-weight: bold;"><u>License Fee</u></font><font style="font-size: 10pt;">. Following receipt by JBI of a Development Candidate Data Package detailing
        that the Development Candidate criteria have been met for <font style="font-weight: bold;">[***]</font> delivery of a JBI <font style="font-weight: bold;">[***]</font> Development Candidate, JBI will select a JBI <font style="font-weight: bold;">[***]</font>
        Development Candidate which will trigger the Option provisions of <u>Article 3</u> and License Fee under <u>Section 6.4</u>.&#160; Notwithstanding, the terms of <u>Sections 3.1</u> and <u>3.2</u>, the Option Deadline for JBI to provide Ionis with
        written notice of its intent to exercise its Option for the JBI <font style="font-weight: bold;">[***]</font> Development Candidate shall be on or before <font style="font-weight: bold;">[***]</font>, and JBI shall pay the Option Fee described in
        <u>Section 6.4</u> no later than the 45<sup style="vertical-align: text-top; line-height: 1; font-size: smaller;">th</sup> day following JBI&#8217;s notice of its intent to exercise such Option.</font></div>
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    <div style="text-align: justify; text-indent: 36pt; font-size: 12pt;"><font style="font-size: 10pt; font-weight: bold;"><u>Post-Licensing Milestone Event Payments</u></font><font style="font-size: 10pt;">. The following Post-Licensing Milestone Event
        payments described in <u>Table 2</u> of <u>Section 6.5</u> are amended as follows solely with respect to the JBI <font style="font-weight: bold;">[***]</font> Development Candidate:</font></div>
    <div>&#160;</div>
    <div>
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            <td style="width: 52%; vertical-align: top;">
              <div style="text-align: justify; font-size: 12pt; font-weight: bold;"><u>Milestone Event Payment</u></div>
            </td>
          </tr>
          <tr>
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              <div style="text-align: justify; font-size: 12pt;">i)</div>
            </td>
            <td style="width: 40%; vertical-align: top;">
              <div style="text-align: justify; font-weight: bold;">[***]</div>
            </td>
            <td style="width: 52%; vertical-align: top;">
              <div style="text-align: justify; font-size: 12pt;">$<font style="font-size: 10pt; font-weight: bold;">[***]</font>; and</div>
            </td>
          </tr>
          <tr>
            <td style="width: 8%; vertical-align: top;">
              <div style="text-align: justify; font-size: 12pt;">ii)</div>
            </td>
            <td style="width: 40%; vertical-align: top;">
              <div style="text-align: justify; font-weight: bold;">[***]</div>
            </td>
            <td style="width: 52%; vertical-align: top;">
              <div style="text-align: justify; font-size: 12pt;">$<font style="font-size: 10pt; font-weight: bold;">[***]</font></div>
            </td>
          </tr>

      </table>
    </div>
    <div>&#160;</div>
    <div style="text-align: center;">*_*_*_*_*_*</div>
    <div style="text-align: center;"> <br>
    </div>
    <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" id="DSPFPageBreakArea">
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            <tr>
              <td style="width: 50.00%;">
                <div>
                  <div style="text-align: left;">December 21, 2016</div>
                </div>
              </td>
              <td style="width: 50.00%;">
                <div>&#160;</div>
              </td>
            </tr>
            <tr>
              <td style="width: 50.00%;">
                <div>&#160;First Amendment</div>
              </td>
              <td style="width: 50.00%;">
                <div>&#160;</div>
              </td>
            </tr>
            <tr>
              <td style="width: 50.00%;">
                <div>&#160;Page&#160;<font id="DSPFPageNumber">5</font> of&#160; 5<br>
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                <div>&#160;</div>
              </td>
            </tr>

        </table>
      </div>
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    <div>Except as otherwise expressly provided herein, the Agreement shall remain in full force and effect without any amendments or modifications.&#160; This First Amendment may be executed in separate counterparts, each of which, whether delivered by
      electronic mail, or otherwise is deemed to be an original, and all of which taken together shall constitute one and the same instrument.&#160; This First Amendment shall be effective as of the First Amendment Effective Date.&#160; If the above reflects your
      understanding of the rights and obligations of the Parties under the Agreement, please acknowledge your agreement of the foregoing by executing the countersignature below.</div>
    <div>&#160;</div>
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        <tr>
          <td style="width: 40%; vertical-align: top;">&#160;</td>
          <td style="width: 60%; vertical-align: top;">
            <div>Very truly yours,</div>
          </td>
        </tr>
        <tr>
          <td style="width: 40%; vertical-align: top;">&#160;</td>
          <td style="width: 60%; vertical-align: top;">&#160;</td>
        </tr>
        <tr>
          <td style="width: 40%; vertical-align: top;">&#160;</td>
          <td style="width: 60%; vertical-align: top;">
            <div style="font-style: italic;"><u>/s/ Austin Clayton</u></div>
          </td>
        </tr>
        <tr>
          <td style="width: 40%; vertical-align: top;">&#160;</td>
          <td style="width: 60%; vertical-align: top;">
            <div>Austin Clayton</div>
          </td>
        </tr>
        <tr>
          <td style="width: 40%; vertical-align: top;">&#160;</td>
          <td style="width: 60%; vertical-align: top;">
            <div>Corporate Secretary</div>
          </td>
        </tr>
        <tr>
          <td style="width: 40%; vertical-align: top;">&#160;</td>
          <td style="width: 60%; vertical-align: top;">
            <div>Janssen Biotech, Inc.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: #000000;" id="z3795332090fc4823a351f086353f4467" border="0" cellpadding="0" cellspacing="0">

        <tr>
          <td colspan="2" style="vertical-align: top;">
            <div>AGREED &amp; ACCEPTED:</div>
          </td>
        </tr>
        <tr>
          <td colspan="2" style="vertical-align: top;">&#160;</td>
        </tr>
        <tr>
          <td colspan="2" style="vertical-align: top;">
            <div style="font-style: italic;"><u>/s/ B. Lynne Parshall</u></div>
          </td>
        </tr>
        <tr>
          <td style="width: 5%; vertical-align: top;">
            <div>Name:</div>
          </td>
          <td style="width: 95%; vertical-align: top;">
            <div><u>B. Lynne Parshall</u></div>
          </td>
        </tr>
        <tr>
          <td style="width: 5%; vertical-align: top;">
            <div style="text-align: justify;">Title:</div>
          </td>
          <td style="width: 95%; vertical-align: top;">
            <div style="text-align: justify;"><u>Chief Operating Officer</u></div>
          </td>
        </tr>
        <tr>
          <td style="width: 5%; vertical-align: top;">
            <div style="text-align: justify;">Date:</div>
          </td>
          <td style="width: 95%; vertical-align: top;">
            <div style="text-align: justify;"><u>December 21, 2016</u></div>
          </td>
        </tr>
        <tr>
          <td style="width: 5%; vertical-align: top;">&#160;</td>
          <td style="width: 95%; vertical-align: top;">&#160;</td>
        </tr>
        <tr>
          <td colspan="2" style="vertical-align: top;">
            <div style="text-align: justify;">Ionis Pharmaceuticals, Inc.</div>
          </td>
        </tr>

    </table>
    <div><br>
    </div>
    <div>&#160;</div>
    <div>
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</DOCUMENT>
<DOCUMENT>
<TYPE>EX-10.61
<SEQUENCE>5
<FILENAME>exhibit10_61.htm
<DESCRIPTION>EXHIBIT 61
<TEXT>
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    <div style="text-align: right; font-weight: bold;">EXHIBIT 10.61</div>
    <div><br>
    </div>
    <div style="text-align: center; font-weight: bold;">IONIS PHARMACEUTICALS, INC.</div>
    <div><br>
    </div>
    <div style="text-align: center; font-weight: bold;">THIRD AMENDED AND RESTATED</div>
    <div style="text-align: center; font-weight: bold;">STRATEGIC ADVISORY SERVICES AGREEMENT (&#8220;<font style="font-style: italic;">SUMMARY PAGE</font>&#8221;)</div>
    <div><br>
    </div>
    <div style="text-align: justify;">This Third Amended and Restated Strategic Advisory Services Agreement is entered into by and between Lyme Pinnacle Consulting Inc., for the services of B. Lynne Parshall, and is made effective as of February 22, 2021,
      and amends and restates the Strategic Advisory Service Agreement dated January 15, 2018, as amended on March 22, 2019 and January 9, 2020, by and between B. Lynne Parshall and Ionis Pharmaceuticals, Inc. (&#8220;<font style="font-weight: bold; font-style: italic;">Ionis</font>&#8221;).</div>
    <div><br>
    </div>
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        <tr>
          <td style="width: 40%; vertical-align: top;">
            <div style="margin-left: 2.8pt;">Date of Third Amended and Restated Strategic Advisory Services Agreement: (&#8220;<font style="font-weight: bold; font-style: italic;">Agreement</font>&#8221;)</div>
          </td>
          <td style="width: 60%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
            <div style="margin-left: 4.45pt;">February 22, 2021 (&#8220;<font style="font-weight: bold; font-style: italic;">3</font><sup style="font-style: italic; font-weight: bold; vertical-align: text-top; line-height: 1; font-size: smaller;">rd</sup><font style="font-weight: bold; font-style: italic;"> A&amp;R Effective Date</font>&#8221;).</div>
          </td>
        </tr>
        <tr>
          <td style="width: 40%; vertical-align: bottom;">
            <div style="margin-left: 2.8pt;">Name of Strategic Advisor:</div>
          </td>
          <td style="width: 60%; vertical-align: bottom; border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
            <div style="margin-right: 0.05pt; margin-left: 4.45pt;">B. Lynne Parshall (hereinafter &#8220;<font style="font-weight: bold; font-style: italic;">Strategic Advisor</font>&#8221;).</div>
          </td>
        </tr>
        <tr>
          <td style="width: 40%; vertical-align: bottom;">
            <div style="margin-left: 2.8pt;">Scope of Strategic Advisory Services:</div>
          </td>
          <td style="width: 60%; vertical-align: bottom; border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
            <div style="margin-right: 0.05pt; margin-left: 4.45pt;">Provide advisory services to Ionis on projects as directed by the CEO.</div>
          </td>
        </tr>
        <tr>
          <td style="width: 40%; vertical-align: bottom;">
            <div style="margin-left: 2.8pt;">Duration of Strategic Advisory Services (the &#8220;<font style="font-weight: bold; font-style: italic;">Strategic Advisory Period</font>&#8221;):</div>
          </td>
          <td style="width: 60%; vertical-align: bottom; border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
            <div style="margin-left: 4.45pt;">Commencing January 1, 2021 and continuing through December 31, 2021.</div>
          </td>
        </tr>
        <tr>
          <td style="width: 40%; vertical-align: top;">
            <div style="margin-right: 18.7pt; margin-left: 2.9pt;">Consideration for Strategic Advisory Services:</div>
          </td>
          <td style="width: 60%; vertical-align: bottom; border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
            <div style="margin-right: 0.05pt; margin-left: 4.45pt;">Annual fee of $600,000 to be paid quarterly.</div>
          </td>
        </tr>

    </table>
    <div><br>
    </div>
    <div style="text-align: justify;">In addition to such compensation, Ionis will reimburse Strategic Advisor for Ionis directed travel, lodging and related expenses or reasonable rate equivalents for lodging, car and meals that Strategic Advisor&#160; incurs
      in the course of performing Strategic Advisory Services under this Agreement.&#160; All such reimbursements will be in accordance with Ionis&#8217; travel policy and Strategic Advisor will provide Ionis with reasonably acceptable supporting documentation.</div>
    <div><br>
    </div>
    <div style="text-align: justify;">Strategic Advisor agrees to provide Ionis with Strategic Advisory Services on the terms described above and according to the additional terms attached hereto as Exhibit A. In this Agreement references to Ionis will
      include Ionis&#8217; affiliate companies where applicable.</div>
    <div><br>
    </div>
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        <tr>
          <td style="width: 15%; vertical-align: top; border-right: 2px solid rgb(0, 0, 0);">&#160;</td>
          <td style="width: 40%; vertical-align: middle; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
            <div style="font-weight: bold;">Lyme Pinnacle Consulting Inc.</div>
          </td>
          <td style="width: 5%; vertical-align: middle; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">&#160;</td>
          <td style="width: 40%; vertical-align: middle; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
            <div style="font-weight: bold;">Ionis Pharmaceuticals, Inc.</div>
          </td>
        </tr>
        <tr>
          <td style="width: 15%; vertical-align: bottom;">
            <div>By (Signature):</div>
          </td>
          <td style="width: 40%; vertical-align: bottom; border-top: 2px solid rgb(0, 0, 0);">
            <div>/s/B. Lynne Parshall</div>
          </td>
          <td style="width: 5%; vertical-align: bottom;">&#160;</td>
          <td style="width: 40%; vertical-align: bottom; border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
            <div>/s/Brett Monia</div>
          </td>
        </tr>
        <tr>
          <td style="width: 15%; vertical-align: bottom;">
            <div>Date:</div>
          </td>
          <td style="width: 40%; vertical-align: bottom; border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
            <div>February 22, 2021</div>
          </td>
          <td style="width: 5%; vertical-align: bottom;">&#160;</td>
          <td style="width: 40%; vertical-align: bottom; border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
            <div>February 22, 2021</div>
          </td>
        </tr>
        <tr>
          <td style="width: 15%; vertical-align: top;">
            <div>Printed Name:</div>
          </td>
          <td style="width: 40%; vertical-align: bottom; border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
            <div>B. Lynne Parshall, for Lyme Pinnacle Consulting Inc.</div>
          </td>
          <td style="width: 5%; vertical-align: bottom;">&#160;</td>
          <td style="width: 40%; vertical-align: bottom; border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
            <div>Brett Monia</div>
          </td>
        </tr>

    </table>
    <div><br>
    </div>
    <div style="text-align: justify; font-weight: bold;">Social Security or Employer Tax ID Number to be provided separately via W-9 form or foreign equivalent.</div>
    <div><br>
    </div>
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      <div id="DSPFPageNumberArea" style="text-align: center;"><font id="DSPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">1 of 7</font></div>
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    <div style="text-align: center; font-weight: bold;">EXHIBIT A</div>
    <div><br>
    </div>
    <div style="text-align: center; font-weight: bold;">TERMS OF STRATEGIC ADVISORY AGREEMENT</div>
    <div><br>
    </div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.</td>
          <td style="width: auto; vertical-align: top;">
            <div style="font-weight: bold;"><u>Engagement of Services</u></div>
          </td>
        </tr>

    </table>
    <div><br>
    </div>
    <div style="text-align: justify;">Strategic Advisor is retained to perform certain services, as needed and requested by Ionis (&#8220;<font style="font-weight: bold; font-style: italic;">Strategic Advisory Services</font>&#8221;). Strategic Advisor will perform
      such Strategic Advisory Services to the best of Strategic Advisor&#8217;s talent and ability.</div>
    <div><br>
    </div>
    <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z3061c7533d914d069ba9b63f0cb24adc">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">2.</td>
          <td style="width: auto; vertical-align: top;">
            <div style="font-weight: bold;"><u>Compensation</u></div>
          </td>
        </tr>

    </table>
    <div><br>
    </div>
    <div style="text-align: justify;">(a)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;As full and complete compensation for Strategic Advisory Services and for the discharge of all of Strategic Advisor&#8217;s obligations hereunder, Ionis will pay Strategic Advisor at the annual rate of $600,000
      to be paid quarterly. Strategic Advisor will submit reimbursable expenses to Ionis electronically, and Ionis, upon its approval, will pay all undisputed fees and expenses within 30 days after Ionis&#8217; receipt of the reimbursement request.</div>
    <div><br>
    </div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; align: right;">(b)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-style: italic;">Ionis Stock Awards:</div>
          </td>
        </tr>

    </table>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;">(i) Since you transitioned seamlessly from an Ionis employee to a nonemployee director, the stock options and RSUs you received for your previous service as an Ionis employee will continue to vest so
      long as your Continuous Service (as defined in the applicable equity plan) continues.</div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;">(ii) Once you are no longer serving on the Ionis board and no longer providing Strategic Advisory Services, to the extent permitted by the terms of the applicable stock option agreement, your vested
      stock options will not terminate until the earlier of 18 months following your retirement or the expiration of the original term of such stock option.</div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;">(iii) For the 18 months following the end of your Ionis board of directors services, if you are eligible for continued health coverage under COBRA, Ionis will pay your COBRA premium payments
      sufficient to continue your coverage at your then current level, or if COBRA is not available, Ionis will pay you an amount equal to the cost of comparable replacement coverage.</div>
    <div><br>
    </div>
    <div>(c)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;While you are providing Strategic Advisory Services, Ionis will make an appropriate level of administrative and technical personnel available to facilitate your performance of Advisory Services at no cost to you, including, without
      limitation IT support and access to Ionis&#8217; electronic calendar and IT systems that are necessary to perform your duties.</div>
    <div><br>
    </div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">3.</td>
          <td style="width: auto; vertical-align: top;">
            <div style="font-weight: bold;"><u>Independent Contractor</u></div>
          </td>
        </tr>

    </table>
    <div><br>
    </div>
    <div style="text-align: justify;">Strategic Advisor is an independent contractor and not an employee of Ionis. Strategic Advisor has no authority to obligate Ionis by contract or otherwise. Strategic Advisor will not be eligible for any employee
      benefits. Taxes will be the sole responsibility of Strategic Advisor.</div>
    <div><br>
    </div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">4.</td>
          <td style="width: auto; vertical-align: top;">
            <div style="font-weight: bold;"><u>Additional Activities</u></div>
          </td>
        </tr>

    </table>
    <div><br>
    </div>
    <div style="text-align: justify;">(a)&#160;&#160;&#160;&#160;&#160;&#160;&#160; Strategic Advisor agrees that during the Strategic Advisory Period and for one year thereafter, Strategic Advisor will not attempt to induce any employee or employees of Ionis to terminate their employment
      with, or otherwise cease their relationship with Ionis.</div>
    <div><br>
    </div>
    <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" id="DSPFPageBreakArea">
      <div id="DSPFPageNumberArea" style="text-align: center;"><font id="DSPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">2 of 7</font></div>
      <div style="page-break-after:always;" id="DSPFPageBreak">
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    </div>
    <div style="text-align: justify;">(b)&#160;&#160;&#160;&#160;&#160;&#160; Strategic Advisor acknowledges that Ionis has developed, through an extensive acquisition process, valuable information regarding actual or prospective partners, licensors, licensees, clients, customers and
      accounts of Ionis (&#8220;<font style="font-weight: bold; font-style: italic;">Trade Secret Information</font>&#8221;). Strategic Advisor acknowledges that Strategic Advisor&#8217;s use of such Trade Secret Information after the termination of the Strategic Advisory
      Period would cause Ionis irreparable harm. Therefore, Strategic Advisor also agrees that Strategic Advisor will not utilize any Trade Secret Information to solicit the business relationship or patronage of any of the actual or prospective partners,
      licensors, licensees, clients, customers or accounts of Ionis.</div>
    <div><br>
    </div>
    <div style="text-align: justify;">(c)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; The restrictions set forth in this Section 4 are considered by the parties to be reasonable for the purposes of protecting Ionis&#8217; business. However, if any such restriction is found by a court of competent
      jurisdiction to be unenforceable because it extends for too long a period of time or over too great a range of activities or in too broad a geographic area, it will be interpreted to extend only over the maximum period of time, range of activities or
      geographic areas as to which it may be enforceable.</div>
    <div><br>
    </div>
    <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z447d6d85bd1b41c990457d24637356c0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">5.</td>
          <td style="width: auto; vertical-align: top;">
            <div style="font-weight: bold;"><u>Confidential Information</u></div>
          </td>
        </tr>

    </table>
    <div><br>
    </div>
    <div style="text-align: justify;">(a)&#160;&#160;&#160;&#160;&#160;&#160;&#160; Ionis possesses confidential information that has been created, discovered, developed by, or otherwise become known to Ionis (including, without limitation, information created, discovered, developed or made
      known by Strategic Advisor arising from the Strategic Advisory Services).</div>
    <div><br>
    </div>
    <div style="text-align: justify;">(i)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;All such information is hereinafter referred to as &#8220;<font style="font-weight: bold; font-style: italic;">Confidential Information</font>.&#8221; By way of illustration, but not limitation, Confidential
      Information includes: (A) inventions, developments, designs, improvements, trade secrets, ideas, formulas, source and object codes, programs, other works of authorship, organisms, plasmids, expression vectors, know-how, processes, cell lines,
      discoveries, techniques, data and documentation systems (hereinafter collectively referred to as &#8220;<font style="font-weight: bold; font-style: italic;">Inventions</font>&#8221;); and (B) information regarding plans for research, development, new products,
      clinical data, pre-clinical product data, clinical trial patient data, marketing and selling, business plans, budgets and unpublished financial statements, licenses, prices and costs, as well as information regarding the skills and compensation of
      employees of Ionis.</div>
    <div><br>
    </div>
    <div style="text-align: justify;">(ii)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;All Confidential Information will be the sole property of Ionis and its assigns, and Ionis and its assigns will be the sole owner of all patents, copyrights and other rights in connection with such
      Confidential Information. At all times, both during the term of this Agreement and for five years after its termination, Strategic Advisor will keep in confidence and trust all Confidential Information and will not use, disclose, lecture upon or
      publish any Confidential Information or anything related to such information without Ionis&#8217; prior written consent. Any permitted disclosures will be made in strict compliance with the Ionis publication and presentation clearance policy.</div>
    <div><br>
    </div>
    <div style="text-align: justify;">(b)&#160;&#160;&#160;&#160;&#160;&#160;&#160; Strategic Advisor also understands that Ionis has received and in the future, will receive valuable information from third parties that is confidential or proprietary (&#8220;<font style="font-weight: bold; font-style: italic;">Third-Party Information</font>&#8221;) subject to a duty on the part of Ionis to maintain the confidentiality of such information and to use it only for certain limited purposes. During the term of this Agreement and for five years
      thereafter, Strategic Advisor will hold Third-Party Information in the strictest confidence and will not disclose or use Third-Party Information except as permitted by the agreement between Ionis and such third party, unless expressly authorized to
      act otherwise by an officer of Ionis in writing. Any permitted disclosures will be made in strict compliance with Ionis publication and presentation clearance policy.</div>
    <div><br>
    </div>
    <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" id="DSPFPageBreakArea">
      <div id="DSPFPageNumberArea" style="text-align: center;"><font id="DSPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">3 of 7</font></div>
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    </div>
    <div style="text-align: justify;">(c)&#160;&#160;&#160;&#160;&#160;&#160;&#160; The obligations of Section 5 will not apply to information that Strategic Advisor can establish by written records: (i) was known by Strategic Advisor prior to the receipt of Confidential Information; (ii)
      was disclosed to Strategic Advisor by a third party having the right to do so; (iii) was, or subsequently became, in the public domain through no fault of Strategic Advisor, its officers, directors, affiliates employees or agents; (iv) was
      independently developed by Strategic Advisor without use of Confidential Information; or (v) was disclosed by Strategic Advisor pursuant to any judicial, governmental or stock exchange request, requirement or order, so long as Strategic Advisor
      provided Ionis with sufficient prior notice in order to allow Ionis to contest such request, requirement or order.</div>
    <div><br>
    </div>
    <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z38f55cb0b1df4708b8a56b8c889d8da6">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">6.</td>
          <td style="width: auto; vertical-align: top;">
            <div style="font-weight: bold;"><u>Inventions</u></div>
          </td>
        </tr>

    </table>
    <div><br>
    </div>
    <div style="text-align: justify;">In the course of performing Strategic Advisory Services for Ionis, Strategic Advisor may develop new ideas or Inventions or make other contributions of value to Ionis.</div>
    <div><br>
    </div>
    <div style="text-align: justify;">(a)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; Strategic Advisor hereby assigns to Ionis Strategic Advisor&#8217;s entire right, title and interest in and to any and all Inventions (and all patent rights, copyrights, and all other rights in connection
      therewith, hereinafter referred to as &#8220;<font style="font-weight: bold; font-style: italic;">Proprietary Rights</font>&#8221;) whether or not patentable or registrable under patent, copyright or similar statutes, made or conceived of or reduced to practice
      or learned by Strategic Advisor, either alone or jointly with others, as a result of performing Strategic Advisory Services hereunder. All Inventions assigned to Ionis pursuant to this section will be known as &#8220;<font style="font-weight: bold; font-style: italic;">Company Inventions</font>&#8221;. Strategic Advisor agrees that all Proprietary Rights and Company Inventions are Ionis&#8217; sole property. Strategic Advisor agrees, upon request, to execute, verify and deliver assignments of such
      Proprietary Rights to Ionis or its designee. Strategic Advisor understands that, to the extent this Agreement will be construed in accordance with the laws of any state which precludes a requirement in an agreement to assign certain classes of
      inventions made by an individual acting as a Strategic Advisor, this section will be interpreted not to apply to any inventions that a court rules and/or Ionis agrees falls within such classes.</div>
    <div><br>
    </div>
    <div style="text-align: justify;">(b)&#160;&#160;&#160;&#160;&#160;&#160;&#160; Strategic Advisor further agrees to assist Ionis in every proper way to obtain, from time to time, and to enforce United States and foreign Proprietary Rights relating to Company Inventions in any and all
      countries. To that end Strategic Advisor will execute, verify and deliver such documents and perform such other acts (including appearances as a witness) as Ionis may reasonably request for use in applying for, obtaining, sustaining and enforcing
      such Proprietary Rights relating to Company Inventions. Strategic Advisor&#8217;s obligation to assist Ionis in obtaining and enforcing Proprietary Rights relating to Company Inventions in any and all countries will continue beyond the termination of this
      Agreement, but Ionis will compensate Strategic Advisor at a reasonable rate after such termination for the time actually spent by Strategic Advisor at Ionis&#8217; request in connection with such assistance. If Ionis is unable, after reasonable effort, to
      secure Strategic Advisor&#8217;s signature on any document needed to apply for or prosecute any Proprietary Rights relating to a Company Invention, Strategic Advisor hereby irrevocably designates and appoints Ionis and its duly authorized officers and
      agents as her agent and attorney in fact, to act for and on Strategic Advisor&#8217;s behalf to execute, verify and file any such applications and to do all other lawfully permitted acts to further the prosecution and issuance of any such Proprietary
      Rights with the same legal force and effect as if executed by Strategic Advisor.</div>
    <div><br>
    </div>
    <div style="text-align: justify;">(c)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;During the term of this Agreement, Strategic Advisor will promptly disclose to Ionis, or&#160;&#160; any persons designated by it, fully and in writing and will hold in trust for the sole right and benefit of Ionis
      any and all Company Inventions, whether or not patentable or protectable by copyright. At the time of each such disclosure, Strategic Advisor will advise Ionis in writing of any Inventions that Strategic Advisor believes are not subject to the
      assignment provisions of Section 6(a) above, and Strategic Advisor will at that time provide to Ionis in writing all evidence necessary to substantiate that belief. Strategic Advisor will not be obligated to disclose information received by Strategic
      Advisor from others under a contract of confidentiality. In addition, after termination of this Agreement, Strategic Advisor will disclose to Ionis all patent applications filed by Strategic Advisor relating to any Company Inventions or relating to
      any work performed by Strategic Advisor on behalf of Ionis.</div>
    <div><br>
    </div>
    <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" id="DSPFPageBreakArea">
      <div id="DSPFPageNumberArea" style="text-align: center;"><font id="DSPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">4 of 7</font></div>
      <div style="page-break-after:always;" id="DSPFPageBreak">
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    </div>
    <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zd7568e2cf6fd4cc9a9ff7171cb6b316f">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">7.</td>
          <td style="width: auto; vertical-align: top;">
            <div style="font-weight: bold;"><u>Previous Strategic Advisory Relationships</u></div>
          </td>
        </tr>

    </table>
    <div><br>
    </div>
    <div style="text-align: justify;">Strategic Advisor represents that Strategic Advisor&#8217;s performance of Strategic Advisory Services, as well as Strategic Advisor&#8217;s performance of the rest of Strategic Advisor&#8217;s obligations under the terms of this
      Agreement, will not breach any agreement to keep in confidence any proprietary information acquired by Strategic Advisor in confidence or in trust from another entity prior to the date of this Agreement. Strategic Advisor agrees not to bring to Ionis
      or to use in the performance of Strategic Advisory Services for Ionis any materials or documents of a present or former employer or client of Strategic Advisor, or any materials or documents obtained by Strategic Advisor under a confidentiality
      agreement imposed by reason of another of Strategic Advisor&#8217;s Strategic Advisory relationships, unless such materials or documents are generally available to the public or Strategic Advisor has authorization from such present or former employer or
      client for the possession and unrestricted use of such materials.</div>
    <div><br>
    </div>
    <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zc013c4cc9c3148ad9d8e77b813fd2f05">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">8.</td>
          <td style="width: auto; vertical-align: top;">
            <div style="font-weight: bold;"><u>Termination; Survival</u></div>
          </td>
        </tr>

    </table>
    <div><br>
    </div>
    <div style="text-align: justify;">(a)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;The term of this Agreement will begin on January 15, 2018 and will end when terminated by either Ionis or Strategic Advisor. Ionis may terminate this Agreement at any time for any reason by providing
      Strategic Advisor at least 90 days advance written notice. Strategic Advisor may terminate this Agreement at any time for any reason by providing Ionis at least 90 days advance written notice; <font style="font-style: italic;">provided</font>, once
      Strategic Advisor delivers such a termination notice, Ionis may elect to accelerate the effective date of such termination. Upon any termination, Ionis will pay Strategic Advisor for any Strategic Advisory Services appropriately rendered and for any
      out of pocket expenses reasonably incurred on behalf of Ionis, up to and including the termination date.</div>
    <div><br>
    </div>
    <div style="text-align: justify;">(b)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;Sections 2(b)(ii) and 2(b)(iii), 9 and 10, will survive termination of this Agreement. In addition, upon expiration or termination of this Agreement, each party will be released from all obligations and
      liabilities to the other occurring or arising after the date of such expiration or termination, except that any termination or expiration of this Agreement will not relieve Strategic Advisor of Strategic Advisor&#8217;s obligations under Sections 4, 5, 6,
      7, 9, 10 and 11 hereof, nor will any such expiration or termination relieve Strategic Advisor or Ionis from any liability arising from any breach of this Agreement. Upon expiration or termination of this Agreement for any reason whatsoever, Strategic
      Advisor will promptly surrender and deliver to Ionis any and all notes, business records, memoranda, specifications, devices, formulas, molecules, cells, storage media, including calculations, sequences, data and other materials of any nature
      pertaining to Strategic Advisory Services for Ionis, as well as any documents or data of any description (or any reproduction of any documents or data) containing or pertaining to any Trade Secret Information, Ionis&#8217; Confidential Information or Third
      Party Information.</div>
    <div><br>
    </div>
    <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z4efbb09d24894fdaa3871d1dab4c5393">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">9.</td>
          <td style="width: auto; vertical-align: top;">
            <div style="font-weight: bold;"><u>Arbitration</u></div>
          </td>
        </tr>

    </table>
    <div><br>
    </div>
    <div style="text-align: justify;">(a)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;Ionis and Strategic Advisor agree to resolve by arbitration all disputes, claims or controversies (&#8220;<font style="font-weight: bold; font-style: italic;">Claims</font>&#8221;), past, present or future, whether or
      not arising out of this Agreement or its termination, that Ionis may have against Strategic Advisor or that Strategic Advisor may have against any of the following (i) Ionis; (ii) Ionis officers, directors; employees or agents; (iii) Ionis&#8217;
      subsidiary or affiliated entities, joint ventures, or joint employers; (iv) Ionis&#8217; benefit plans or the plans&#8217; sponsors, fiduciaries, administrators, affiliates and agents; and/or (v) all successors and assigns of any of the foregoing. The Claims
      covered by this Agreement include all disputes that Ionis or Strategic Advisor could otherwise pursue in state or federal court including, but not limited to, Claims based on any state, federal, or local statute, regulation or ordinance (including
      Claims for discrimination, retaliation, harassment, unpaid wages or violation of state or federal wage and hour laws), as well as common law Claims (including Claims for breach of contract, breach of the implied covenant of good faith and fair
      dealing, wrongful discharge, defamation, misrepresentation, fraud, or infliction of emotional distress). Ionis and Strategic Advisor anticipates that this Section 9 provides the benefits of a speedy, less formal, impartial, final and binding dispute
      resolution procedure.</div>
    <div><br>
    </div>
    <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" id="DSPFPageBreakArea">
      <div id="DSPFPageNumberArea" style="text-align: center;"><font id="DSPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">5 of 7</font></div>
      <div style="page-break-after:always;" id="DSPFPageBreak">
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    </div>
    <div style="text-align: justify;">(b)&#160;&#160;&#160;&#160;&#160;&#160;&#160; To the maximum extent permitted by law, Strategic Advisor hereby waives any right to bring on behalf of persons other than Strategic Advisor, or to otherwise participate with other persons in, any class,
      collective or representative action (i.e. a type of lawsuit in which one or several persons sue on behalf of a larger group of persons).</div>
    <div><br>
    </div>
    <div style="text-align: justify;">(c)&#160;&#160;&#160;&#160;&#160;&#160; The arbitration will be conducted by a single neutral arbitrator in accordance with the then- current Commercial Arbitration and Mediation Procedures of the American Arbitration Association (&#8220;<font style="font-weight: bold; font-style: italic;">AAA</font>&#8221;). The arbitration will take place in San Diego, California. Ionis will pay the arbitrator&#8217;s fee and will bear all administrative charges by AAA. All parties will be entitled to engage in
      reasonable pre-hearing discovery to obtain information to prosecute or defend the asserted claims. Any disputes between the parties regarding the nature or scope of discovery will be decided by the arbitrator. The arbitrator will hear and issue a
      written ruling upon any dispositive motions brought by either party, including but not limited to, motions for summary judgment or summary adjudication of issues. After the hearing, the arbitrator will issue a written decision setting forth the
      award, if any, and explaining the basis therefore. The arbitrator will have the power to award any type of relief that would be available in court. The arbitrator&#8217;s award will be final and binding upon the parties and may be entered as a judgment in
      any court of competent jurisdiction. If there is conflict in the arbitration procedures set forth in this Agreement and the AAA rules specified above, the AAA rules will control. Notwithstanding the foregoing, and regardless of what is provided by
      the AAA rules, the arbitrator will not have authority or jurisdiction to consolidate claims of different individuals or entities into one proceeding, nor will the arbitrator have authority or jurisdiction to hear the arbitration as a class action. As
      noted above, Strategic Advisor has agreed to waive any right to bring any class, collective or representative action. To the extent that the class, collective or representative action waiver described above is not enforceable, the issue of whether to
      certify any alleged or putative class for a class action proceeding must be decided by a court of competent jurisdiction. The arbitrator will not have authority or jurisdiction to decide class certification, collective or representative action
      issues. Until any class certification, collective, or representative action issues are decided by the court, all arbitration proceedings will be stayed, and the arbitrator will take no action with respect to the matter. However, once any issues
      regarding class certification, collective, or representative action have been decided by the court, the arbitrator will have authority to decide the substantive claims.</div>
    <div><br>
    </div>
    <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z8eb54261c0b049baac585c2890ae031d">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">10.</td>
          <td style="width: auto; vertical-align: top;">
            <div style="font-weight: bold;"><u>Indemnification</u></div>
          </td>
        </tr>

    </table>
    <div><br>
    </div>
    <div style="text-align: justify;">(a)&#160;&#160;&#160;&#160;&#160;&#160;&#160; Ionis will indemnify, defend and hold Strategic Advisor harmless against any and all losses, costs, expenses and damages (including reasonable attorney&#8217;s fees) (&#8220;Loss(es)&#8221;) incurred as a result of any third
      party claims, suits, actions, demands or proceedings resulting or arising from the performance of Strategic Advisory Services as specifically directed by Ionis in accordance with the Agreement to the extent such Loss(es) are not the result of
      Strategic Advisor&#8217;s gross negligence, intentional misconduct or material breach of this Agreement.</div>
    <div><br>
    </div>
    <div style="text-align: justify;">(b)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;Ionis&#8217; agreement to indemnify, defend and hold Strategic Advisor harmless is conditioned upon the Strategic Advisor (i) providing written notice to Ionis of any claim, demand or action arising out of the
      indemnified activities within thirty (30) days after Strategic Advisor has knowledge of such claim, demand or action, <font style="font-style: italic;">provided </font>that the failure to so notify Ionis shall not relieve Ionis of its obligations
      hereunder except to the extent such failure shall have actually materially prejudiced Ionis; (ii) permitting Ionis to assume full responsibility to investigate, prepare for and defend against any such claim or demand; (iii) assisting Ionis, at Ionis&#8217;
      reasonable expense, in the investigation of, preparation of and defense of any such claim or demand; (iv) undertaking reasonable steps to mitigate any loss, damage or expense with respect to the applicable claim or demand; and (v) not settling such
      claim or demand without Ionis&#8217; prior written consent.</div>
    <div><br>
    </div>
    <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" id="DSPFPageBreakArea">
      <div id="DSPFPageNumberArea" style="text-align: center;"><font id="DSPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">6 of 7</font></div>
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    </div>
    <div style="text-align: justify;">(c)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;Ionis will endeavor to include Strategic Advisor as a covered attorney on its insurance policy for attorneys who advise Ionis.</div>
    <div><br>
    </div>
    <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zfb559e36a8ee41d9acc7fd22e6410dd8">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">11.</td>
          <td style="width: auto; vertical-align: top;">
            <div style="font-weight: bold;"><u>Miscellaneous</u></div>
          </td>
        </tr>

    </table>
    <div><br>
    </div>
    <div style="text-align: justify;">(a)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;The rights and liabilities of the parties hereto will bind and inure to the benefit of their respective successors, heirs, executors and administrators, as the case may be; <font style="font-style: italic;">provided that</font>, as Ionis has specifically contracted for Strategic Advisor&#8217;s services, Strategic Advisor may not assign or delegate Strategic Advisor&#8217;s obligations under this Agreement either in whole or in part without Ionis&#8217; prior
      written consent.</div>
    <div><br>
    </div>
    <div style="text-align: justify;">(b)&#160;&#160;&#160;&#160;&#160;&#160; Because Strategic Advisor&#8217;s services are personal and unique and because Strategic Advisor has access to and become acquainted with Ionis&#8217; Confidential Information, the parties agree that in the event of a
      threatened or actual material breach of this Agreement by Strategic Advisor injunctive relief would be appropriate. As such, Ionis has the right to enforce this Agreement and any of its provisions by injunction, specific performance or other
      equitable relief without prejudice to any other rights and remedies that Ionis may have for a breach of this Agreement.</div>
    <div><br>
    </div>
    <div style="text-align: justify;">(c)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; This Agreement will be governed by and construed according to the laws of the State of California as such laws are applied to contracts entered into and performed entirely within such State. If any
      provision of this Agreement is held to be or becomes invalid, illegal or unenforceable, such provision will be validly reformed to approximate as nearly as possible the intent of the parties and the remainder of this Agreement will not be affected
      thereby and will remain valid and enforceable to the greatest extent permitted by law.</div>
    <div><br>
    </div>
    <div style="text-align: justify;">(d)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;This Agreement, and all other documents mentioned herein, constitute the final, exclusive and complete understanding and agreement of the parties hereto and supersedes all prior understandings and
      agreements. Any waiver, modification or amendment of any provision of this Agreement will be effective only if in writing and signed by the parties hereto.</div>
    <div><br>
    </div>
    <div style="text-align: justify;">(e)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;Any notices required or permitted hereunder will be given to the appropriate party at the address specified on the Summary Page or at such other address as the party will specify in writing. Such notice
      will be deemed given upon personal delivery to the appropriate address, or by facsimile transmission (receipt verified and with confirmation copy followed by another permitted method), sent by express courier service, or, if sent by certified or
      registered mail, three (3) days after the date of mailing.</div>
    <div><br>
    </div>
    <div><br>
    </div>
    <div style="font-size: 8pt; text-align: center;"><font id="DSPFPageNumber" style="font-weight: normal; font-style: normal;">7 of 7</font></div>
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<DOCUMENT>
<TYPE>EX-10.79
<SEQUENCE>6
<FILENAME>exhibit10_79.htm
<DESCRIPTION>EXHIBIT 79
<TEXT>
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      <div style="text-align: right; font-weight: bold;">EXHIBIT 10.79</div>
      <div><br>
      </div>
      <div style="font-weight: bold;">CERTAIN IDENTIFIED INFORMATION HAS BEEN EXCLUDED FROM THE EXHIBIT BECAUSE IT IS BOTH (I) NOT MATERIAL AND (II) WOULD BE COMPETITIVELY HARMFUL IF PUBLICLY DISCLOSED. SUCH EXCLUDED INFORMATION HAS BEEN MARKED WITH
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      <div style="text-align: center; font-weight: bold;">AMENDMENT NO. 3</div>
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      <div>This Amendment No. 3 (the &#8220;<font style="font-weight: bold; font-style: italic;">Amendment</font>&#8221;) to the Strategic Collaboration Agreement dated July 31, 2015, as previously amended by Amendment No. 1 dated October 18, 2018, and Amendment No. 2
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              <div>ASTRAZENECA AB, a company incorporated in Sweden under no. 556011-7482 with its registered office at SE-151 85 S&#246;dert&#228;lje, Sweden (&#8220;<font style="font-weight: bold; font-style: italic;">AstraZeneca</font>&#8221;) and</div>
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              <div>IONIS PHARMACEUTICALS, INC., a Delaware corporation, (formally known as Isis Pharmaceuticals, Inc.) having its principal place of business at 2855 Gazelle Court, Carlsbad, California 92010 (&#8220;<font style="font-weight: bold; font-style: italic;">Ionis</font>&#8221;),</div>
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      <div>and is made effective as of December 17, 2020 (the &#8220;<font style="font-weight: bold; font-style: italic;">Amendment Effective Date</font>&#8221;).</div>
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      <div style="font-weight: bold;">Recitals</div>
      <div><br>
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      <div>WHEREAS, the Parties desire to amend the Agreement to extend the Disease Research Term.</div>
      <div><br>
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      <div>NOW, THEREFORE, in consideration of the mutual covenants contained in this Amendment, and other good and valuable consideration, the receipt and sufficiency of which are hereby acknowledged, the Parties, intending to be legally bound, agree as
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      <div><br>
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      <div style="font-weight: bold;">Agreement</div>
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            <td style="width: 18pt; vertical-align: top; align: right;">1.</td>
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              <div style="font-weight: bold;"><u>Definitions</u></div>
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      <div><br>
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      <div style="margin-left: 18pt;">Any capitalized term not separately defined in this Amendment shall have the meaning ascribed to it in the Agreement.</div>
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            <td style="width: 18pt; vertical-align: top; align: right;">2.</td>
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              <div style="font-weight: bold;"><u>Modifications</u></div>
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      <div style="margin-left: 18pt;"><u>Section 1.3.2</u> of the Agreement is hereby deleted in its entirety and replaced with the following:</div>
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      <div style="margin-left: 18pt;">&#8220;1.3.2. <font style="font-weight: bold;"><u>Disease Research Term</u></font>. The term for the conduct of the Disease Research Program will begin on the Effective Date and will end on the [***] anniversary of the
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              <div style="font-weight: bold;"><u>Amendment Effective Date</u></div>
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      <div style="margin-left: 18pt;">This Amendment shall become effective on the Amendment Effective Date.</div>
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              <div style="font-weight: bold;"><u>Entire Agreement</u></div>
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      <div style="margin-left: 18pt;">The Agreement together with this Amendment constitutes the entire agreement between the Parties with respect to the subject matter of the Agreement. The Agreement together with this Amendment supersedes all prior
        agreements, whether written or oral, with respect to the subject matter of the Agreement. Each Party confirms that it is not relying on any representations, warranties, or covenants of the other Party except as specifically set out in the Agreement
        or this Amendment. Nothing in this Amendment is intended to limit or exclude any liability or fraud. The Parties hereby agree that subject to the modifications specifically stated in this Amendment, all other terms and conditions of the Agreement
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      <div style="margin-left: 18pt; font-weight: bold;"><u>Execution</u></div>
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      <div style="margin-left: 18pt;">THIS AMENDMENT IS EXECUTED by the authorized representatives of the Parties as of the date first written above.</div>
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              <div><font style="font-weight: bold;">ASTRAZENECA AB</font> (publ.)</div>
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            <td style="width: 1.54%; vertical-align: top;">&#160;</td>
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              <div style="font-weight: bold;">IONIS PHARMACEUTICALS, INC.</div>
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            <td style="width: 10%; vertical-align: top;">&#160;</td>
            <td style="width: 39%; vertical-align: top;">&#160;</td>
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              <div>Signature:</div>
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              <div><u>/s/ Regina Fritsche Danielson</u></div>
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              <div>Signature:</div>
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              <div><u>/s/ Brett Monia</u></div>
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            <td style="width: 39%; vertical-align: top;">&#160;</td>
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              <div>Name:</div>
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              <div><u>Regina Fritsche Danielson</u></div>
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              <div>Name:</div>
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              <div><u>Brett Monia</u></div>
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            <td style="width: 10%; vertical-align: top;">&#160;</td>
            <td style="width: 39%; vertical-align: top;">&#160;</td>
            <td style="width: 1.54%; vertical-align: top;">&#160;</td>
            <td style="width: 10%; vertical-align: top;">&#160;</td>
            <td style="width: 39%; vertical-align: top;">&#160;</td>
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              <div>Title:</div>
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              <div><u>SVP and Head of Research and</u></div>
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              <div>Title:</div>
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              <div><u>CEO</u></div>
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            <td style="width: 10%; vertical-align: top;">&#160;</td>
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              <div><u>Early Development, Cardiovascular,</u></div>
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            <td style="width: 1.54%; vertical-align: top;">&#160;</td>
            <td style="width: 10%; vertical-align: top;">&#160;</td>
            <td style="width: 39%; vertical-align: top;">&#160;</td>
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              <div><u>Renal and Metabolism</u></div>
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            <td style="width: 1.54%; vertical-align: top;">&#160;</td>
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<DOCUMENT>
<TYPE>EX-10.80
<SEQUENCE>7
<FILENAME>exhibit10_80.htm
<DESCRIPTION>EXHIBIT 80
<TEXT>
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      <div style="color: rgb(255, 0, 0); font-weight: bold;">Execution Copy</div>
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      <div style="text-align: right; font-weight: bold;">EXHIBIT 10.80</div>
      <div style="text-align: center;"><img width="161" height="53" src="image17.jpg"></div>
      <div>&#160;</div>
      <div style="text-align: center; font-weight: bold;">IONIS PHARMACEUTICALS, INC.</div>
      <div style="text-align: center; font-weight: bold;">ADVISORY SERVICES AGREEMENT</div>
      <div style="text-align: center; font-weight: bold;">(&#8220;<font style="font-style: italic;">SUMMARY PAGE</font>&#8221;)</div>
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              <div>Date of Advisory Services Agreement: (&#8220;<font style="font-weight: bold; font-style: italic;">Agreement</font>&#8221;)</div>
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              <div>December 17, 2020 (&#8220;<font style="font-weight: bold; font-style: italic;">Effective Date</font>&#8221;).</div>
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              <div>Name of Advisor:</div>
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              <div>Stanley T. Crooke (hereinafter &#8220;<font style="font-weight: bold; font-style: italic;">Advisor</font>&#8221;).</div>
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            <td style="width: 40%; vertical-align: bottom;">
              <div>Scope of Advisory Services:</div>
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              <div>As set forth on Schedule A attached hereto.</div>
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              <div>Duration of Advisory Services (the &#8220;<font style="font-weight: bold; font-style: italic;">Advisory Period</font>&#8221;):</div>
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              <div>An initial term beginning immediately following the June 2, 2021 Annual Stockholders Meeting and ending on June 30, 2023 unless extended or terminated in accordance with Section 8 of Exhibit A below.</div>
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          <tr>
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              <div>Consideration for Advisory Services:</div>
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              <div>As set forth on Schedule B attached hereto.</div>
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              <div>Time Provided by Advisor:</div>
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            <td style="width: 60%; vertical-align: bottom; border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
              <div>As set forth on Schedule A attached hereto.</div>
            </td>
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      <div style="text-align: justify;">In addition to such compensation, Ionis Pharmaceuticals, Inc. (&#8220;<font style="font-weight: bold; font-style: italic;">Ionis</font>&#8221;) will reimburse Advisor for Ionis approved travel and other out-of-pocket costs
        reasonably incurred in the course of performing Advisory Services under this Agreement as further described on Schedule B attached hereto. Advisor shall be permitted to travel at first-class level on commercial carriers.</div>
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      <div style="text-align: justify;">Advisor agrees to provide Ionis with Advisory Services on the terms described above and according to the additional terms attached hereto as Exhibit A.&#160; In this Agreement references to Ionis, including but not
        limited to Sections 3-6 of Exhibit A, will include Ionis&#8217; affiliate companies where applicable.</div>
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            <td style="width: 10%; vertical-align: top; padding-bottom: 2px;">&#160;</td>
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              <div style="font-weight: bold;">Advisor</div>
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              <div style="font-weight: bold;">Ionis Pharmaceuticals, Inc.</div>
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              <div>By (Signature):</div>
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              <div>/s/ Stanley T. Crooke</div>
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              <div>/s/ Joseph H. Wender</div>
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            <td rowspan="1" style="width: 44%; vertical-align: top; border-bottom: 2px solid rgb(0, 0, 0);">&#160;</td>
            <td rowspan="1" style="width: 1.89%; vertical-align: top; padding-bottom: 2px;">&#160;</td>
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              <div>Printed Name:</div>
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              <div>Stanley T. Crooke</div>
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            <td style="width: 1.89%; vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
            <td style="width: 44%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
              <div>Joseph H. Wender - Chair of Nominating &amp; Governance Committee</div>
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              <div>By (Signature):</div>
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              <div>NA</div>
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              <div>/s/ Spencer R. Berthelsen</div>
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            <td rowspan="1" style="width: 44%; vertical-align: top; border-bottom: 2px solid rgb(0, 0, 0);">&#160;</td>
            <td rowspan="1" style="width: 1.89%; vertical-align: top; padding-bottom: 2px;">&#160;</td>
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              <div>Printed Name:</div>
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              <div>NA</div>
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            <td style="width: 44%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
              <div>Spencer R. Berthelsen &#8211; Chair of Compensation Committee</div>
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              <div>Address:</div>
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              <div>Provided Separately</div>
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              <div>2855 Gazelle Court,</div>
              <div>Carlsbad, CA 92010</div>
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              <div>Telephone:</div>
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              <div>Provided Separately</div>
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            <td style="width: 44%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
              <div>760-931-9200</div>
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              <div>Fax:</div>
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              <div>Provided Separately</div>
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            <td style="width: 1.89%; vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
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              <div>760-603-3820</div>
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              <div>e-mail:</div>
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              <div>Provided Separately</div>
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            <td style="width: 1.89%; vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
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          </tr>

      </table>
      <div><br>
      </div>
      <div style="font-weight: bold;">Social Security or Employer Tax ID Number to be provided separately via W-9 form or foreign equivalent.</div>
      <div style="font-weight: bold;"> <br>
      </div>
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      </div>
      <div style="color: rgb(255, 0, 0); font-weight: bold;">Execution Copy</div>
      <div><br>
      </div>
      <div style="text-align: center; font-weight: bold;">EXHIBIT A</div>
      <div><br>
      </div>
      <div style="text-align: center; font-weight: bold;">TERMS OF ADVISORY AGREEMENT</div>
      <div><br>
      </div>
      <div style="text-align: justify;">1.&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; &#160;&#160; <font style="font-weight: bold;"><u>Engagement of Services; Transition From Executive Chairman to Advisor; Press Release</u></font></div>
      <div><br>
      </div>
      <div style="text-align: justify;">Advisor is retained to perform certain services during the Advisory Period, as needed and requested by Ionis, which services are specifically described on Schedule A attached hereto (&#8220;<font style="font-weight: bold; font-style: italic;">Advisory Services</font>&#8221;).&#160; Advisor will perform such Advisory Services to the best of Advisor&#8217;s talent and ability.</div>
      <div><br>
      </div>
      <div style="text-align: justify;">Advisor hereby voluntarily retires and resigns from his position as an employee and member of the Board of Directors of Ionis, which resignation will take effect immediately following the June 2, 2021 Annual
        Stockholders Meeting</div>
      <div><br>
      </div>
      <div style="text-align: justify;">Promptly following the Effective Date of this Agreement, Ionis will announce Advisor&#8217;s retirement and transition to his role as Advisor pursuant to a press release drafted by Ionis and approved by Advisor (such
        approval not to be unreasonably withheld, conditioned or delayed).</div>
      <div><br>
      </div>
      <div style="text-align: justify;">2.&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; &#160;&#160; <font style="font-weight: bold;"><u>Compensation</u></font></div>
      <div><br>
      </div>
      <div style="text-align: justify;">As full and complete compensation for Advisory Services and for the discharge of all of Advisor&#8217;s obligations hereunder, Ionis will pay Advisor at the rate set forth on Schedule B attached hereto and provide the
        other consideration set forth on Schedule B. Advisor will invoice Ionis on a quarterly basis for Advisor fees and reimbursable expenses, and Ionis, upon its approval, will pay all undisputed fees and expenses within 30 days after Ionis&#8217; receipt of
        the invoice.</div>
      <div><br>
      </div>
      <div style="text-align: justify;">3.&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; &#160;&#160; <font style="font-weight: bold;"><u>Independent Contractor</u></font></div>
      <div><br>
      </div>
      <div style="text-align: justify;">Advisor is an independent contractor and not an employee of Ionis.&#160; Advisor has no authority to obligate Ionis by contract or otherwise.&#160; &#160; Taxes will be the sole responsibility of Advisor.</div>
      <div><br>
      </div>
      <div style="text-align: justify;">4.&#160;&#160;&#160;&#160;&#160;&#160;&#160; &#160; &#160; <font style="font-weight: bold;"><u>Additional Activities</u></font></div>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z4158de44465340a3b785f80bc14db714">

          <tr>
            <td style="width: 36pt; vertical-align: top;">(a)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>Advisor agrees that during the Advisory Period and for one year thereafter, Advisor will not attempt to induce any employee or employees of Ionis to terminate their employment with, or otherwise cease their relationship with Ionis.</div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z2705668b3de14715b426daff57b04e78">

          <tr>
            <td style="width: 36pt; vertical-align: top;">(b)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>Advisor acknowledges that Ionis has developed, through an extensive acquisition process, valuable information regarding actual or prospective partners, licensors, licensees, clients, customers and accounts of Ionis (&#8220;<font style="font-weight: bold; font-style: italic;">Trade Secret Information</font>&#8221;). Advisor acknowledges that Advisor&#8217;s use of such Trade Secret Information after the termination of the Advisory Period would cause Ionis irreparable harm.
                Therefore, Advisor also agrees that Advisor will not utilize any Trade Secret Information to solicit the business relationship or patronage of any of the actual or prospective partners, licensors, licensees, clients, customers or accounts
                of Ionis.</div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" id="DSPFPageBreakArea">
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      </div>
      <div style="color: rgb(255, 0, 0); font-weight: bold;">Execution Copy</div>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z572cd7c4724c4fcb92b120b9679d6e90">

          <tr>
            <td style="width: 36pt; vertical-align: top;">(c)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>The restrictions set forth in this Section 4 are considered by the parties to be reasonable for the purposes of protecting Ionis&#8217; business.&#160; However, if any such restriction is found by a court of competent jurisdiction to be
                unenforceable because it extends for too long a period of time or over too great a range of activities or in too broad a geographic area, it will be interpreted to extend only over the maximum period of time, range of activities or
                geographic areas as to which it may be enforceable.</div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <div style="text-align: justify;">5.&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; &#160;&#160; <font style="font-weight: bold;"><u>Confidential Information; No disparagement</u></font></div>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zf9a41500329f4e1aa73530bfdf12f99f">

          <tr>
            <td style="width: 36pt; vertical-align: top;">(a)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>Ionis possesses confidential information that has been created, discovered, developed by, or otherwise become known to Ionis (including, without limitation, information which is&#160; created, discovered, developed or made known by Advisor
                arising from the Advisory Services).</div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z446261d808774674887b676488ac7498">

          <tr>
            <td style="width: 36pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">(i)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>All such information is hereinafter referred to as &#8220;<font style="font-weight: bold; font-style: italic;">Confidential Information</font>.&#8221;&#160; By way of illustration, but not limitation, Confidential Information includes:&#160; (A) inventions,
                developments, designs, improvements, trade secrets, ideas, formulas, source and object codes, programs, other works of authorship, organisms, plasmids, expression vectors, know-how, processes, cell lines, discoveries, techniques, data and
                documentation systems (hereinafter collectively referred to as &#8220;<font style="font-weight: bold; font-style: italic;">Inventions</font>&#8221;); and (B) information regarding plans for research, development, new products, clinical data,
                pre-clinical product data, clinical trial patient data, marketing and selling, business plans, budgets and unpublished financial statements, licenses, prices and costs, as well as information regarding the skills and compensation of
                employees of Ionis.</div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z0f5d81247cf7473c87fdf493098693ba">

          <tr>
            <td style="width: 36pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;">(ii)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>All Confidential Information will be the sole property of Ionis and its assigns, and Ionis and its assigns will be the sole owner of all patents, copyrights and other rights in connection with such Confidential Information.&#160; At all
                times, both during the term of this Agreement and for five years after its termination, Advisor will keep in confidence and trust all Confidential Information and will not use, disclose, lecture upon or publish any Confidential Information
                or anything related to such information without Ionis&#8217; prior written consent or as otherwise reasonably necessary in furtherance of Advisor performing the Advisory Services.&#160; Any permitted disclosures will be made in strict compliance with
                the Ionis publication and presentation clearance policy.</div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z40d02715597f41769db028419b6de38e">

          <tr>
            <td style="width: 36pt; vertical-align: top;">(b)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>Advisor also understands that Ionis has received and in the future, will receive valuable information from third parties that is confidential or proprietary (&#8220;<font style="font-weight: bold; font-style: italic;">Third-Party Information</font>&#8221;)


                subject to a duty on the part of Ionis to maintain the confidentiality of such information and to use it only for certain limited purposes.&#160; During the term of this Agreement and for five years thereafter, Advisor will hold Third-Party
                Information in the strictest confidence and will not disclose or use Third-Party Information except as permitted by the agreement between Ionis and such third party, unless expressly authorized to act otherwise by an officer of Ionis in
                writing or as otherwise reasonably necessary in furtherance of Advisor performing the Advisory Services.&#160; Any permitted disclosures will be made in strict compliance with Ionis publication and presentation clearance policy.</div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" id="DSPFPageBreakArea">
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      </div>
      <div style="color: rgb(255, 0, 0); font-weight: bold;">Execution Copy</div>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z4ef0a07ed7d8437c872bfd734d3e3251">

          <tr>
            <td style="width: 36pt; vertical-align: top;">(c)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>The obligations of Section 5 will not apply to information that Advisor can establish by written records: (i) was known by Advisor prior to the receipt of Confidential Information; (ii) was disclosed to Advisor by a third party having
                the right to do so; (iii) was, or subsequently became, in the public domain through no fault of Advisor, its officers, directors, affiliates employees or agents; (iv) was independently developed by Advisor without use of Confidential
                Information; or (v) was disclosed by Advisor pursuant to any judicial, governmental or stock exchange request, requirement or order, so long as Advisor, if legally permitted, provided Ionis with sufficient prior notice in order to allow
                Ionis to contest such request, requirement or order. Advisor may also disclose Confidential Information to his legal counsel and financial advisor and as reasonably necessary pursuant to any litigation between Advisor and Ionis or any of
                its affiliates.</div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zd67b60c2f4a7457588b95e9edbb0c6fc">

          <tr>
            <td style="width: 36pt; vertical-align: top;">(d)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>Ionis agrees that its executive officers and the current members of its Board of Directors and the heads of the Investor Relations and Corporate Communication Departments) will not disparage or knowingly make false or defamatory
                statements regarding Advisor in any manner whatsoever (including through the use of any social networking sites, blogs, forums or any similar medium, including in response to inquiries from other users of such medium) whether directly or
                indirectly through a third party. Advisor agrees that he will not disparage or knowingly make false or defamatory statements about Ionis, or its directors, officers, or affiliates in any manner whatsoever (including through the use of any
                social networking sites, blogs, forums or any similar medium, including in response to inquiries from other users of such medium) whether directly or indirectly through a third party. This Section shall not apply to communications (i)
                required by law, court order or subpoena, (ii)&#160; that are otherwise privileged as a matter of law, (iii) that are made to correct inaccurate or misleading statements made about Advisor or Ionis, as applicable or (iv) that are reasonably
                appropriate to be made in connection with any litigation between Advisor and Ionis or its affiliates. Advisor&#8217;s and Ionis&#8217; non-disparagement obligations under this Section do not interfere with or restrict his or its ability to communicate
                with any federal, state, or local agency, including any with which a charge has been filed.</div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <div style="text-align: justify;">6.&#160;&#160;&#160;&#160;&#160;&#160;&#160; &#160; &#160; <font style="font-weight: bold;"><u>Inventions</u></font></div>
      <div><br>
      </div>
      <div style="text-align: justify;">In the course of performing Advisory Services for Ionis, Advisor may develop new ideas or Inventions or make other contributions of value to Ionis.</div>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zcfd6907052434ec99bdc8a1758d54a36">

          <tr>
            <td style="width: 36pt; vertical-align: top;">(a)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>Advisor hereby assigns to Ionis Advisor&#8217;s entire right, title and interest in and to any and all Inventions (and all patent rights, copyrights, and all other rights in connection therewith, hereinafter referred to as &#8220;<font style="font-weight: bold; font-style: italic;">Proprietary Rights</font>&#8221;) whether or not patentable or registrable under patent, copyright or similar statutes, made or conceived of or reduced to practice or learned by Advisor, either
                alone or jointly with others, as a result of performing Advisory Services hereunder.&#160; All Inventions assigned to Ionis pursuant to this section will be known as &#8220;<font style="font-weight: bold; font-style: italic;">Company Inventions</font>&#8221;.&#160;


                Advisor agrees that all Proprietary Rights and Company Inventions are Ionis&#8217; sole property.&#160; Advisor agrees, upon request, to execute, verify and deliver assignments of such Proprietary Rights to Ionis or its designee.&#160; Advisor understands
                that, to the extent this Agreement will be construed in accordance with the laws of any state which precludes a requirement in an agreement to assign certain classes of inventions made by an individual acting as an Advisor, this section
                will be interpreted not to apply to any inventions that a court rules and/or Ionis agrees falls within such classes.</div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
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      </div>
      <div style="color: rgb(255, 0, 0); font-weight: bold;">Execution Copy</div>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z03e5822ffa0548ec9b925639768a743a">

          <tr>
            <td style="width: 36pt; vertical-align: top;">(b)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>Advisor further agrees to assist Ionis in every proper way to obtain, from time to time, and to enforce United States and foreign Proprietary Rights relating to Company Inventions in any and all countries.&#160; To that end Advisor will
                execute, verify and deliver such documents and perform such other acts (including appearances as a witness) as Ionis may reasonably request for use in applying for, obtaining, sustaining and enforcing such Proprietary Rights relating to
                Company Inventions.&#160; Advisor&#8217;s obligation to assist Ionis in obtaining and enforcing Proprietary Rights relating to Company Inventions in any and all countries will continue beyond the termination of this Agreement, but Ionis will
                compensate Advisor at a reasonable rate after such termination for the time actually spent by Advisor at Ionis&#8217; request in connection with such assistance.&#160; If Ionis is unable, after reasonable effort, to secure Advisor&#8217;s signature on any
                document needed to apply for or prosecute any Proprietary Rights relating to a Company Invention, Advisor hereby irrevocably designates and appoints Ionis and its duly authorized officers and agents as&#160; her agent and attorney in fact, to
                act for and on Advisor&#8217;s behalf to execute, verify and file any such applications and to do all other lawfully permitted acts to further the prosecution and issuance of any such Proprietary Rights with the same legal force and effect as if
                executed by Advisor.</div>
            </td>
          </tr>

      </table>
      <div style="text-align: justify; text-indent: -36pt; margin-left: 36pt;"> <br>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z82909cd3bb7840b38207cd71e12cf53e">

          <tr>
            <td style="width: 36pt; vertical-align: top;">(d)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>During the term of this Agreement, Advisor will promptly disclose to Ionis, or any persons designated by it, fully and in writing and will hold in trust for the sole right and benefit of Ionis any and all Company Inventions, whether or
                not patentable or protectable by copyright.&#160; At the time of each such disclosure, Advisor will advise Ionis in writing of any Inventions that Advisor believes are not subject to the assignment provisions of Section 6(a) above, and Advisor
                will at that time provide to Ionis in writing all evidence necessary to substantiate that belief.&#160; Advisor will not be obligated to disclose information received by Advisor from others under a contract of confidentiality.&#160; In addition,
                after termination of this Agreement, Advisor will disclose to Ionis all patent applications filed by Advisor relating to any Company Inventions or relating to any work performed by Advisor on behalf of Ionis.</div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <div style="text-align: justify;">7.&#160;&#160;&#160;&#160;&#160; &#160;&#160; &#160;&#160; <font style="font-weight: bold;"><u>Previous Advisory Relationships</u></font></div>
      <div><br>
      </div>
      <div style="text-align: justify;">Advisor represents that Advisor&#8217;s performance of Advisory Services, as well as Advisor&#8217;s performance of the rest of Advisor&#8217;s obligations under the terms of this Agreement, will not breach any agreement to keep in
        confidence any proprietary information acquired by Advisor in confidence or in trust from another entity prior to the date of this Agreement.&#160; Advisor agrees not to bring to Ionis or to use in the performance of Advisory Services for Ionis any
        materials or documents of a present or former employer or client of Advisor, or any materials or documents obtained by Advisor under a confidentiality agreement imposed by reason of another of Advisor&#8217;s Advisory relationships, unless such materials
        or documents are generally available to the public or Advisor has authorization from such present or former employer or client for the possession and unrestricted use of such materials.</div>
      <div><br>
      </div>
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      </div>
      <div style="color: rgb(255, 0, 0); font-weight: bold;">Execution Copy</div>
      <div><br>
      </div>
      <div style="text-align: justify;">8.&#160;&#160;&#160;&#160;&#160;&#160;&#160; &#160; &#160; <font style="font-weight: bold;"><u>Termination; Survival</u></font></div>
      <div><br>
      </div>
      <div style="text-align: justify;">(a)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;This Agreement will become effective on the Effective Date and will end on June 30, 2023 unless the parties mutually agree by written amendment to extend this Agreement.&#160; If Ionis believes that Advisor
        is in material breach of this Agreement, then Ionis may deliver notice of such material breach to Advisor. If the breach is curable, Advisor will have 60 days to cure such breach. If Advisor fails to cure such breach within the 60 day period, or if
        the breach is not subject to cure, Ionis may terminate this Agreement by providing written notice to Advisor. Without limiting the foregoing, the intentional material breach by Advisor of Section 5 of this Agreement constitutes a material breach of
        this Agreement.</div>
      <div><br>
      </div>
      <div style="text-align: justify;">(b)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;The last sentence of the second paragraph of Schedule B and the last paragraph of Schedule B will survive termination of this Agreement.&#160; In addition, except as referenced in the immediately preceding
        sentence, upon expiration or termination of this Agreement, each party will be released from all obligations and liabilities to the other occurring or arising after the date of such expiration or termination, except that any termination or
        expiration of this Agreement will not relieve Advisor of Advisor&#8217;s obligations under Sections 4, 5, 6, 7, 9, 10 and 11 hereof, nor will any such expiration or termination relieve Advisor or Ionis from any liability arising from any breach of this
        Agreement.&#160; Upon expiration or termination of this Agreement for any reason whatsoever, Advisor will promptly surrender and deliver to Ionis any and all notes, business records, memoranda, specifications, devices, formulas, molecules, cells,
        storage media, including calculations, sequences, data and other materials of any nature pertaining to Advisory Services for Ionis, as well as any documents or data of any description (or any reproduction of any documents or data) containing or
        pertaining to any Trade Secret Information, Ionis&#8217; Confidential Information or Third Party Information.</div>
      <div><br>
      </div>
      <div style="text-align: justify;">9.&#160;&#160;&#160;&#160;&#160;&#160;&#160; &#160; &#160; <font style="font-weight: bold;"><u>Arbitration</u></font></div>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zac9ff094314e47768eff83a384a30f0c">

          <tr>
            <td style="width: 36pt; vertical-align: top;">(a)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>Ionis and Advisor agree to resolve by arbitration all disputes, claims or controversies (&#8220;<font style="font-weight: bold; font-style: italic;">Claims</font>&#8221;), past, present or future,&#160; whether or not arising out of this Agreement or its
                termination, that Ionis may have against Advisor or that Advisor may have against any of the following (i) Ionis; (ii) Ionis officers, directors; employees or agents; (iii) Ionis&#8217; subsidiary or affiliated entities, joint ventures, or joint
                employers; (iv) Ionis&#8217; benefit plans or the plans&#8217; sponsors, fiduciaries, administrators, affiliates and agents; and/or (v) all successors and assigns of any of the foregoing.&#160; The Claims covered by this Agreement include all disputes that
                Ionis or Advisor could otherwise pursue in state or federal court including, but not limited to, Claims based on any state, federal, or local statute, regulation or ordinance (including Claims for discrimination, retaliation, harassment,
                unpaid wages or violation of state or federal wage and hour laws), as well as common law Claims (including Claims for breach of contract, breach of the implied covenant of good faith and fair dealing, wrongful discharge, defamation,
                misrepresentation, fraud, or infliction of emotional distress).&#160; Ionis and Advisor anticipates that this Section 9 provides the benefits of a speedy, less formal, impartial, final and binding dispute resolution procedure.</div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" id="DSPFPageBreakArea">
        <div id="DSPFPageNumberArea" style="text-align: center;"><font id="DSPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">6 of 9</font></div>
        <div style="page-break-after:always;" id="DSPFPageBreak">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <div style="color: rgb(255, 0, 0); font-weight: bold;">Execution Copy</div>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z85c3cdce4e504498a9854238548e7fba">

          <tr>
            <td style="width: 36pt; vertical-align: top;">(b)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>To the maximum extent permitted by law, Advisor hereby waives any right to bring on behalf of persons other than Advisor, or to otherwise participate with other persons in, any class, collective or representative action (i.e. a type of
                lawsuit in which one or several persons sue on behalf of a larger group of persons).</div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z64d02fc1aea144b7ad0e36f1b4fea9bc">

          <tr>
            <td style="width: 36pt; vertical-align: top;">(c)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>The arbitration will be conducted by a single neutral arbitrator in accordance with the then-current Commercial Arbitration and Mediation Procedures of the American Arbitration Association (&#8220;<font style="font-weight: bold; font-style: italic;">AAA</font>&#8221;).&#160; The arbitration will take place in San Diego, California.&#160; Ionis will pay the arbitrator&#8217;s fee and will bear all administrative charges by AAA.&#160; All parties will be entitled to engage in reasonable pre-hearing
                discovery to obtain information to prosecute or defend the asserted claims.&#160; Any disputes between the parties regarding the nature or scope of discovery will be decided by the arbitrator.&#160; The arbitrator will hear and issue a written ruling
                upon any dispositive motions brought by either party, including but not limited to, motions for summary judgment or summary adjudication of issues.&#160; After the hearing, the arbitrator will issue a written decision setting forth the award, if
                any, and explaining the basis therefore.&#160; The arbitrator will have the power to award any type of relief that would be available in court.&#160; The arbitrator&#8217;s award will be final and binding upon the parties and may be entered as a judgment
                in any court of competent jurisdiction.&#160; If there is conflict in the arbitration procedures set forth in this Agreement and the AAA rules specified above, the AAA rules will control.&#160; Notwithstanding the foregoing, and regardless of what is
                provided by the AAA rules, the arbitrator will not have authority or jurisdiction to consolidate claims of different individuals or entities into one proceeding, nor will the arbitrator have authority or jurisdiction to hear the arbitration
                as a class action.&#160; As noted above, Advisor has agreed to waive any right to bring any class, collective or representative action.&#160; To the extent that the class, collective or representative action waiver described above is not enforceable,
                the issue of whether to certify any alleged or putative class for a class action proceeding must be decided by a court of competent jurisdiction.&#160; The arbitrator will not have authority or jurisdiction to decide class certification,
                collective or representative action issues.&#160; Until any class certification, collective, or representative action issues are decided by the court, all arbitration proceedings will be stayed, and the arbitrator will take no action with
                respect to the matter.&#160; However, once any issues regarding class certification, collective, or representative action have been decided by the court, the arbitrator will have authority to decide the substantive claims.</div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <div style="text-align: justify;">10.&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<font style="font-weight: bold;"><u>Indemnification; Representations</u></font></div>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z924ad8f205ed44dd82d8f94e92e054b9">

          <tr>
            <td style="width: 36pt; vertical-align: top;">(a)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>Ionis will indemnify, defend and hold Advisor harmless against any and all losses, costs, expenses and damages (including advancement of reasonable attorney&#8217;s fees) (<font style="font-weight: bold; font-style: italic;">&#8220;Loss(es)&#8221;</font>)
                incurred as a result of any third party claims, suits, actions, demands or proceedings resulting or arising&#160; from the performance of Advisory Services as specifically directed by Ionis in accordance with the Agreement to the extent such
                Loss(es) are not the result of Advisor&#8217;s gross negligence, intentional misconduct or material breach of this Agreement.</div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" id="DSPFPageBreakArea">
        <div id="DSPFPageNumberArea" style="text-align: center;"><font id="DSPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">7 of 9</font></div>
        <div style="page-break-after:always;" id="DSPFPageBreak">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <div style="color: rgb(255, 0, 0); font-weight: bold;">Execution Copy</div>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z525bd19b2cd9489fb1c6b6e3b9c9289e">

          <tr>
            <td style="width: 36pt; vertical-align: top;">(b)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>Ionis&#8217; agreement to indemnify, defend and hold&#160; Advisor harmless is conditioned upon the Advisor (i) providing written notice to Ionis of any claim, demand or action arising out of the indemnified activities within thirty (30) days after
                Advisor has knowledge of such claim, demand or action, provided that the failure to so notify Ionis shall not relieve Ionis of its obligations hereunder except to the extent such failure shall have actually materially prejudiced Ionis; (ii)
                permitting Ionis to assume full responsibility to investigate, prepare for and defend against any such claim or demand; (iii) assisting Ionis, at Ionis&#8217; reasonable expense, in the investigation of, preparation of and defense of any such
                claim or demand; (iv) undertaking reasonable steps to mitigate any loss, damage or expense with respect to the applicable claim or demand; and (v) not settling such claim or demand without Ionis&#8217; prior written consent.</div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z69b351e5a7c0455ea5d288965aeeee8b">

          <tr>
            <td style="width: 36pt; vertical-align: top;">(c)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>Advisor represents and warrants to Ionis that (i) Advisor has complied in all material respects with his fiduciary duties and responsibilities as an officer and member of the board of directors of Ionis and (ii) Advisor is not aware of
                any set of facts or circumstances that may reasonably give rise to litigation or other legal proceeding between Advisor and Ionis. Ionis represents and warrants to Advisor that Ionis is not aware of any set of facts or circumstances that
                may reasonably give rise to litigation or other legal proceeding between Ionis and Advisor.</div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <div style="text-align: justify;">11.&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<font style="font-weight: bold;"><u>Miscellaneous</u></font></div>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z9a6ba253db094044b433229a4aced9f4">

          <tr>
            <td style="width: 36pt; vertical-align: top;">(a)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>The rights and liabilities of the parties hereto will bind and inure to the benefit of their respective successors, heirs, executors and administrators, as the case may be; <font style="font-style: italic;">provided that</font>, as
                Ionis has specifically contracted for Advisor&#8217;s services, Advisor may not assign or delegate Advisor&#8217;s obligations under this Agreement either in whole or in part without Ionis&#8217; prior written consent, and Ionis may not assign Ionis&#8217;
                obligations under this Agreement either in whole or in part without Advisor&#8217;s prior written consent, other than in connection with a corporate transaction resulting in a sale of Ionis or substantially all of its assets.</div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zf6ff5e1fa10e4734ac7241db8ffdd191">

          <tr>
            <td style="width: 36pt; vertical-align: top;">(b)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>Because Advisor&#8217;s services are personal and unique and because Advisor has access to and become acquainted with Ionis&#8217; Confidential Information, the parties agree that in the event of a threatened or actual material breach of this
                Agreement by Advisor injunctive relief would be appropriate.&#160; As such, Ionis has the right to enforce this Agreement and any of its provisions by injunction, specific performance or other equitable relief without prejudice to any other
                rights and remedies that Ionis may have for a breach of this Agreement.</div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z1128584fa453487a8b4d642c0ab2f78c">

          <tr>
            <td style="width: 36pt; vertical-align: top;">(c)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>This Agreement will be governed by and construed according to the laws of the State of California as such laws are applied to contracts entered into and performed entirely within such State.&#160; If any provision of this Agreement is held to
                be or becomes invalid, illegal or unenforceable, such provision will be validly reformed to approximate as nearly as possible the intent of the parties and the remainder of this Agreement will not be affected thereby and will remain valid
                and enforceable to the greatest extent permitted by law.</div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" id="DSPFPageBreakArea">
        <div id="DSPFPageNumberArea" style="text-align: center;"><font id="DSPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">8 of 9</font></div>
        <div style="page-break-after:always;" id="DSPFPageBreak">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <div style="color: rgb(255, 0, 0); font-weight: bold;">Execution Copy</div>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zbe32efca2454496290a2440e20443ed0">

          <tr>
            <td style="width: 36pt; vertical-align: top;">(d)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>This Agreement, and all other documents mentioned herein, constitute the final, exclusive and complete understanding and agreement of the parties hereto and supersedes all prior understandings and agreements; provided the employee
                proprietary information and invention agreement between Advisor and Ionis will remain in full force and effect.&#160; Any waiver, modification or amendment of any provision of this Agreement will be effective only if in writing and signed by the
                parties hereto.</div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z7350cc7f966b46f6892d913b9309fa19">

          <tr>
            <td style="width: 36pt; vertical-align: top;">(e)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>Any notices required or permitted hereunder will be given to the appropriate party at the address specified on the Summary Page or at such other address as the party will specify in writing.&#160; Such notice will be deemed given upon
                personal delivery to the appropriate address, or by facsimile transmission (receipt verified and with confirmation copy followed by another permitted method), sent by express courier service, or, if sent by certified or registered mail,
                three (3) days after the date of mailing.</div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z09672005f6414a98b0efac2baf832dce">

          <tr>
            <td style="width: 36pt; vertical-align: top;">(f)</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>Each party will execute, acknowledge and deliver such further instruments, and do all such other acts, as may be necessary or appropriate in order to carry out the expressly stated purposes and the clear intent of this Agreement.</div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: #000000;" id="ze0c69301780c4fcaa56f5aa153e43b01">

          <tr>
            <td style="width: 100%; vertical-align: top; background-color: rgb(242, 242, 242);">
              <div style="text-align: center; font-weight: bold;">[END OF EXHIBIT A]</div>
            </td>
          </tr>

      </table>
      <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" id="DSPFPageBreakArea">
        <div id="DSPFPageNumberArea" style="text-align: center;"><font id="DSPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">9 of 9</font></div>
        <div style="page-break-after:always;" id="DSPFPageBreak">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <div style="color: rgb(255, 0, 0); font-weight: bold;">Execution Copy</div>
      <div><br>
      </div>
      <div style="text-align: center; font-weight: bold;">SCHEDULE&#160; A</div>
      <div><br>
      </div>
      <div style="text-align: center; font-weight: bold;">Advisory Services</div>
      <div><br>
      </div>
      <div>As requested by Ionis&#8217; CEO or Chairman of the Board of Directors you will provide the following advisory services:</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z015ceda44d9543b192ee1b5897275aeb">

          <tr>
            <td style="width: 18pt;"><br>
            </td>
            <td style="width: 18pt; vertical-align: top;">&#8226;</td>
            <td style="width: auto; vertical-align: top;">
              <div>Participate in and provide advice regarding drug discovery and development decisions (RMC/DMC, advice to teams as requested)</div>
            </td>
          </tr>

      </table>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="ze70af62a2de7467cb41a4f790471e20d">

          <tr>
            <td style="width: 18pt;"><br>
            </td>
            <td style="width: 18pt; vertical-align: top;">&#8226;</td>
            <td style="width: auto; vertical-align: top;">
              <div>Participate in advancing the science at Ionis via program reviews, Core antisense research meetings (CAR) and other activities as reasonably&#160; requested</div>
            </td>
          </tr>

      </table>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zc64f6e9e49754362885175ef829072b1">

          <tr>
            <td style="width: 18pt;"><br>
            </td>
            <td style="width: 18pt; vertical-align: top;">&#8226;</td>
            <td style="width: auto; vertical-align: top;">
              <div>Lead the scientific activities for the Crooke Group (Ionis Dept #260)</div>
            </td>
          </tr>

      </table>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zc499e4dedb1f4f3494e455112f67cef5">

          <tr>
            <td style="width: 18pt;"><br>
            </td>
            <td style="width: 18pt; vertical-align: top;">&#8226;</td>
            <td style="width: auto; vertical-align: top;">
              <div>Participate as a key spokesman for Ionis&#8217; technology</div>
            </td>
          </tr>

      </table>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zcab0c2d0f5fb4e4b9b86b45d2dbab1f0">

          <tr>
            <td style="width: 18pt;"><br>
            </td>
            <td style="width: 18pt; vertical-align: top;">&#8226;</td>
            <td style="width: auto; vertical-align: top;">
              <div>Participate as a key spokesman for Ionis when requested by and coordinated with Ionis; provided communications regarding Ionis&#8217; management or strategy will be Ionis&#8217; sole responsibility.</div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <div>While you are providing such services, Ionis will provide administrative assistance to you with the same personnel (i.e. Kim Butler) at the same level of service as you received during your tenure as Executive Chairman.&#160; If Ms. Butler applies
        for another position within Ionis for which she is qualified, Ionis will reasonably consider her application for the position.&#160; As such, if Ms. Butler&#8217;s service with Ionis terminates or she voluntarily takes another position within Ionis, Ionis
        will provide an appropriate level of administrative assistance to you.&#160; Ionis will also provide appropriate office space for you and your administrative support when you are on site at Ionis&#8217; facilities.</div>
      <div><br>
      </div>
      <div>In addition, Ionis will provide an appropriate level of technical personnel available to facilitate your performance of Advisory Services at no cost to you, including, without limitation IT support and access to Ionis&#8217; electronic calendar,
        files&#160; and IT systems that are necessary to perform your duties.</div>
      <div> <br>
      </div>
      <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" id="DSPFPageBreakArea">
        <div id="DSPFPageFooter" style="width: 100%;">
          <table cellspacing="0" cellpadding="0" border="0" id="zf2008830a12d4043aa357cc02ce0276b" style="font-family: 'Times New Roman'; font-size: 10pt; color: #000000; width: 100%;">

              <tr>
                <td style="width: 50%; font-size: 8pt;">Schedule A<br>
                </td>
                <td style="width: 50%; text-align: right; font-size: 8pt;">Page 1<br>
                </td>
              </tr>

          </table>
        </div>
        <div style="page-break-after:always;" id="DSPFPageBreak">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <div style="color: rgb(255, 0, 0); font-weight: bold;">Execution Copy</div>
      <div><br>
      </div>
      <div style="text-align: center; font-weight: bold;">SCHEDULE&#160; B</div>
      <div><br>
      </div>
      <div style="text-align: center; font-weight: bold;">Compensation for Advisory Services</div>
      <div><br>
      </div>
      <div>For your Advisory services, starting after the June 2021 annual meeting of stockholders, Ionis will pay you at the rate of $100,000 per calendar quarter, payable in accordance with Section 2 of the Agreement. If this agreement is extended past
        the 2022 &#8211; 2023 service year payment for services will be set by mutual written agreement between you and Ionis, based on the expected services for such year</div>
      <div><br>
      </div>
      <div>Since you are transitioning seamlessly from an Ionis employee to a consultant, the stock options and RSUs you received for your previous service as an Ionis employee (collectively, <font style="font-weight: bold; font-style: italic;">&#8220;Employee
          Equity Awards&#8221;</font>) will continue to vest so long as your Continuous Service (as defined in the applicable equity plan) continues. For the avoidance of doubt,&#160; your Advisory Services shall be treated as Continuous Service. If your Continuous
        Service terminates during the term of this Agreement&#160; or upon the expiration of this Agreement (other than for a termination by Ionis for your material breach of this Agreement), your Employee Equity Awards that are not vested will become
        immediately vested upon such termination. Upon the closing of a Change in Control of Ionis (as defined in the Amended and Restated Ionis Pharmaceuticals, Inc. 2011 Equity Incentive Plan), your Employee Equity Awards that are not vested will become
        immediately vested. Any vested stock options held by Advisor shall continue to remain exercisable while Advisor is providing Continuous Service and the applicable exercise period shall continue following termination of Continuous Service as if such
        termination were a termination of employment.</div>
      <div><br>
      </div>
      <div>From the end of your Ionis board of directors services through June 30, 2023, if you are eligible for continued health coverage under COBRA, Ionis will pay your COBRA premium payments sufficient to continue your coverage at your then current
        level, or if COBRA is not available, Ionis will pay you on a monthly basis an amount equal to the cost of comparable replacement coverage.</div>
      <div><br>
      </div>
      <div><br>
      </div>
      <div>
        <div>
          <table cellspacing="0" cellpadding="0" border="0" style="font-family: 'Times New Roman'; font-size: 10pt; color: #000000; width: 100%;">

              <tr>
                <td style="width: 50%; font-size: 8pt;">Schedule B<br>
                </td>
                <td style="width: 50%; text-align: right; font-size: 8pt;">Page 1<br>
                </td>
              </tr>

          </table>
          <div>
            <hr noshade="noshade" align="center" style="height: 2px; color: #000000; background-color: #000000; text-align: center; margin-left: auto; margin-right: auto; border: none;"></div>
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</DOCUMENT>
<DOCUMENT>
<TYPE>EX-10.81
<SEQUENCE>8
<FILENAME>exhibit10_81.htm
<DESCRIPTION>EXHIBIT 81
<TEXT>
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    <title></title>
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    <div>
      <div style="text-align: right; font-weight: bold;">EXHIBIT 10.81</div>
      <div><br>
      </div>
      <div style="font-weight: bold;">CERTAIN IDENTIFIED INFORMATION HAS BEEN EXCLUDED FROM THE EXHIBIT BECAUSE IT IS BOTH (I) NOT MATERIAL AND (II) WOULD BE COMPETITIVELY HARMFUL IF PUBLICLY DISCLOSED.&#160; SUCH EXCLUDED INFORMATION HAS BEEN MARKED WITH
        &#8220;[***]&#8221;.</div>
      <div><br>
      </div>
      <div>December 31, 2020</div>
      <div><br>
      </div>
      <div>Biogen MA Inc.</div>
      <div>225 Binney Street</div>
      <div>Cambridge, MA 02142</div>
      <div>Attention: Chief Legal Officer</div>
      <div>Email: <font style="font-weight: bold;">[***]</font>@biogen.com</div>
      <div><br>
      </div>
      <div style="text-indent: 36pt; font-weight: bold;">Re:&#160; <a name="z_Hlk64369233"></a>[***] Collaboration Program</div>
      <div>&#160;</div>
      <div>Dear Anabella:</div>
      <div>&#160;</div>
      <div style="text-align: justify; text-indent: 36pt;">Reference is hereby made to that certain New Strategic Neurology Drug Discovery and Development Collaboration, Option and License Agreement between Ionis Pharmaceuticals, Inc. (&#8220;<font style="font-weight: bold; font-style: italic;">Ionis</font>&#8221;) and Biogen MA Inc. (&#8220;<font style="font-weight: bold; font-style: italic;">Biogen</font>&#8221;) dated April 19, 2018, as supplemented or amended to date (the &#8220;<font style="font-weight: bold; font-style: italic;">Agreement</font>&#8221;). Any capitalized terms not defined herein will have the meaning set forth in the Agreement.</div>
      <div>&#160;</div>
      <div style="text-align: justify; text-indent: 36pt;">WHEREAS, Biogen <a name="z_cp_text_1_3"></a>and Ionis have discussed the use of certain drug delivery technology, including <font style="font-weight: bold;">[***]</font> (each a &#8220;<font style="font-weight: bold;">[***]</font>&#8221;) and <font style="font-weight: bold;">[***]</font> (each, a &#8220;<font style="font-weight: bold;">[***]</font>&#8221;), in each case targeting the <font style="font-weight: bold;">[***]</font>;</div>
      <div>&#160;</div>
      <div style="text-align: justify; text-indent: 36pt;">WHEREAS, Biogen has identified certain specific <font style="font-weight: bold;">[***]</font>and specific <font style="font-weight: bold;">[***]</font>;</div>
      <div>&#160;</div>
      <div style="text-align: justify; text-indent: 36pt;">WHEREAS, as of the date hereof, the Neurology Target <font style="font-weight: bold;">[***]</font> is a High Interest Target;</div>
      <div>&#160;</div>
      <div style="text-align: justify; text-indent: 36pt;">WHEREAS, as of the date hereof, the Parties are pursuing a Collaboration Program consisting of a Strategy directed against <font style="font-weight: bold;">[***]</font> for <font style="font-weight: bold;">[***]</font> (such Strategy, the &#8220;<font style="font-weight: bold;">[***] </font><font style="font-weight: bold; font-style: italic;">Strategy</font>,&#8221; and such Collaboration Program, the &#8220;<font style="font-weight: bold;">[***] </font><font style="font-weight: bold; font-style: italic;">Collaboration Program</font>&#8221;); and</div>
      <div>&#160;</div>
      <div style="text-align: justify; text-indent: 36pt;">WHEREAS, the Parties desire to (i) designate an alternative Strategy directed to <font style="font-weight: bold;">[***]</font> pursuant to which the Parties would <font style="font-weight: bold;">[***]</font>
        (as defined below) with an <font style="font-weight: bold;">[***]</font> directed against <font style="font-weight: bold;">[***]</font> for <font style="font-weight: bold;">[***] </font>and (ii)<font style="font-weight: bold; font-style: italic;">&#160;</font>designate such Strategy directed to <font style="font-weight: bold;">[***]</font> as an additional Collaboration Program under the Agreement (such Strategy, the &#8220;<font style="font-weight: bold;">[***] </font><font style="font-weight: bold; font-style: italic;">Strategy</font>,&#8221; and such Collaboration Program, the &#8220;<font style="font-weight: bold;">[***] </font><font style="font-weight: bold; font-style: italic;">Collaboration Program</font>&#8221;).</div>
      <div>&#160;</div>
      <div style="text-align: justify; text-indent: 36pt;">NOW, THEREFORE, for the promises set forth herein and valuable consideration (the receipt and adequacy of which is hereby acknowledged), solely with respect to <font style="font-weight: bold;">[***]</font>,
        the Parties agree to modify the Agreement as follows:</div>
      <div style="text-align: justify; text-indent: 36pt;"> <br>
      </div>
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          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <div style="text-align: justify; text-indent: 18pt;">1.&#160;&#160;&#160; <font style="font-weight: bold;"><u>Selection of [***]</u></font>.&#160; Each <font style="font-weight: bold;">[***] </font>or <font style="font-weight: bold;">[***] </font>provided by Biogen
        to Ionis under this letter agreement or the Agreement and identified by Biogen by sequence will be a &#8220;<font style="font-weight: bold; font-style: italic;">Biogen </font><font style="font-weight: bold;">[***]</font>&#8221; or &#8220;<font style="font-weight: bold; font-style: italic;">Biogen </font><font style="font-weight: bold;">[***]</font>,&#8221; respectively (collectively, the &#8220;<font style="font-weight: bold; font-style: italic;">Biogen </font><font style="font-weight: bold;">[***]</font>&#8221;).&#160; The
        Parties will select the final Biogen <font style="font-weight: bold;">[***] </font>for inclusion in the <font style="font-weight: bold;">[***]</font> Development Candidate and such selection will be reflected in the minutes of the Neurology JRC
        or Neurology JDC.</div>
      <div>&#160;</div>
      <div style="text-align: justify; text-indent: 18pt;">2.&#160;&#160; <font style="font-weight: bold;"><u>Designation of [***]</u></font><font style="font-weight: bold;">&#160;</font><font style="font-weight: bold;"><u>Collaboration Program; Target Designation
            Milestone Payment</u></font>.&#160; The Parties hereby (a) designate the <font style="font-weight: bold;">[***] </font>Strategy as an alternative Strategy directed to <font style="font-weight: bold;">[***]</font> and (b) designate the <font style="font-weight: bold;">[***] </font>Strategy as a Collaboration Program. Notwithstanding any provision to the contrary set forth in the Agreement, the Target Designation Milestone for the <font style="font-weight: bold;">[***] </font>Strategy

        will be <font style="font-weight: bold;">[***]</font>.&#160; Such payment will be due and payable no later than <font style="font-weight: bold;">[***]</font> (<font style="font-weight: bold;">[***]</font>) Business Days after the date of receipt an
        invoice therefor from Ionis.</div>
      <div>&#160;</div>
      <div style="text-align: justify; text-indent: 18pt;">3.&#160;&#160; <font style="font-weight: bold;"><u>Supply of [***]</u></font>.&#160; Notwithstanding any provision to the contrary set forth in the Agreement, including <u>Section 1.8.6</u> (Manufacturing and
        Supply for Collaboration Programs), before the License Effective Date with respect to the <font style="font-weight: bold;">[***]</font> Strategy, to the extent necessary, Biogen, at its expense, will supply research-grade <font style="font-weight: bold;">[***] </font>to Ionis sufficient to (a) support the Research and Development activities under the <font style="font-weight: bold;">[***]</font> Strategy as set forth in the applicable Development Candidate
        Identification Plan, and (b) support IND-Enabling Toxicology Studies pursuant to the applicable Toxicology Strategy. Notwithstanding any provision to the contrary set forth in the Agreement, including <u>Section 1.8.4</u> (IND-Enabling Toxicology
        Studies), unless the Neurology JDC agrees otherwise, Biogen will conduct and lead, all IND-Enabling Toxicology Studies for all Development Candidates under the <font style="font-weight: bold;">[***] </font>Collaboration Program, in accordance
        with the applicable IND-Enabling Toxicology Study design <a name="z_cp_text_1_4"></a>and Toxicology Strategy (that are each approved pursuant to <u>Section 1.8.4</u> (IND-Enabling Toxicology Studies)) and the <a name="z_cp_text_1_6"></a>other
        terms of the Agreement.</div>
      <div>&#160;</div>
      <div style="text-align: justify; text-indent: 18pt;">4.&#160;&#160;&#160; <font style="font-weight: bold;"><u>Materials</u></font>.&#160; To facilitate the conduct of activities under the <font style="font-weight: bold;">[***]</font> Collaboration Program or the
        performance of other activities for such Collaboration Program under the Agreement or this letter agreement, Biogen may provide to Ionis or its Affiliates certain compositions of matter, biological materials, or chemical compounds Controlled by
        Biogen, including the Biogen <font style="font-weight: bold;">[***]</font>, for use by Ionis (such materials or compounds and any progeny and derivatives thereof, collectively, &#8220;<font style="font-weight: bold; font-style: italic;">Materials</font>&#8221;).

        Except as otherwise set forth in this Agreement, all such Materials will remain the sole property of Biogen, will be used only in the fulfillment of obligations or exercise of rights under the Agreement expressly in accordance with the applicable
        Neurology Plan or other written agreement by the Parties as to the use thereof, subject to any limitations specified in writing by Biogen in connection with such provision, which restrictions will not further limit Ionis&#8217; rights under this letter
        agreement or the Agreement, will not be used or delivered to or for the benefit of any Third Party without the prior written consent of Biogen (except as expressly permitted under the applicable Neurology Plan), and will not be used in research or
        testing involving human subjects, unless expressly agreed by Biogen.&#160; Without limiting the foregoing, Ionis will not reverse engineer, disassemble, modify, create, or engineer any type of <font style="font-weight: bold;">[***]</font> from, any
        Biogen <font style="font-weight: bold;">[***]</font>, Biogen <font style="font-weight: bold;">[***]</font>, Biogen <font style="font-weight: bold;">[***]</font>, or Biogen <font style="font-weight: bold;">[***] </font>provided to Ionis under
        the Agreement or this letter agreement.&#160; Except as otherwise set forth in the Agreement or in this letter agreement, THE MATERIALS ARE PROVIDED &#8220;AS IS&#8221; AND WITHOUT ANY REPRESENTATION OR WARRANTY, EXPRESS OR IMPLIED, INCLUDING ANY IMPLIED WARRANTY
        OF MERCHANTABILITY OR OF FITNESS FOR ANY PARTICULAR PURPOSE OR ANY WARRANTY THAT THE USE OF THE MATERIALS WILL NOT INFRINGE OR VIOLATE ANY PATENT RIGHT OR OTHER PROPRIETARY RIGHTS OF ANY THIRD PARTY.</div>
      <div style="text-align: justify; text-indent: 18pt;"> <br>
      </div>
      <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" id="DSPFPageBreakArea">
        <div style="page-break-after:always;" id="DSPFPageBreak">
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      </div>
      <div style="text-align: justify; text-indent: 18pt;">5.&#160;&#160; <font style="font-weight: bold;"><u>Interpretation</u></font>.&#160; Solely with respect to the <font style="font-weight: bold;">[***] </font>Collaboration Program, <u>Section 1.8.6</u>
        (Manufacturing and Supply for Collaboration Programs) and <u>Section 4.8.2(c)</u> (API and Product) of the Agreement are hereby amended as follows:</div>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zb754b5a429f24808b4f32798b9b8c8a0">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 18pt; vertical-align: top; align: right;">a.</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>In <u>Section 1.8.6</u> (Manufacturing and Supply for Collaboration Programs), the terms &#8220;ASO&#8221; and &#8220;API&#8221; will be deemed to exclude any <font style="font-weight: bold;">[***] </font>or <font style="font-weight: bold;">[***] </font>that

                is incorporated into any Compound, Development Candidate, or Product; and</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z2415d14715864e3297ee5e8ad87a3791">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 18pt; vertical-align: top; align: right;">b.</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>In <u>Section 4.8.2(c)</u> (API and Product), the terms &#8220;bulk Development Candidate,&#8221; &#8220;API,&#8221; &#8220;Clinical Supplies&#8221; and &#8220;Finished Drug Product&#8221; will be deemed to include any ASO that is incorporated into the applicable Compound,
                Development Candidate or Product, whether alone or in combination with any <font style="font-weight: bold;">[***] </font>or <font style="font-weight: bold;">[***]</font>.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <div style="text-align: justify; text-indent: 18pt;">6.&#160;&#160; <font style="font-weight: bold;"><u>Initiation of IND-Enabling Toxicology Study</u></font>.&#160; There will be <font style="font-weight: bold;">[***]</font> under <u>Section 6.3</u> (Milestone
        Payments for First Initiation of IND-Enabling Toxicology Studies) for the <font style="font-weight: bold;">[***] </font>Milestone with respect to the <font style="font-weight: bold;">[***] </font>Collaboration Program.</div>
      <div>&#160;</div>
      <div style="text-align: justify; text-indent: 18pt;">7.&#160;&#160;&#160; <font style="font-weight: bold;"><u>License Fee</u></font>.&#160; Notwithstanding any provision to the contrary set forth in the Agreement, including <u>Section 6.4</u> (License Fee), the Option
        Fee for the <font style="font-weight: bold;">[***] </font>Collaboration Program will be $<font style="font-weight: bold;">[***]</font>.</div>
      <div>&#160;</div>
      <div style="text-align: justify; text-indent: 18pt;">8.&#160;&#160;&#160; <font style="font-weight: bold;"><u>[***] Post-Option Development Milestone Payments</u></font>.&#160; If a Product under the <font style="font-weight: bold;">[***] </font>Collaboration Program
        is classified as a <font style="font-weight: bold;">[***] </font>under the Agreement in accordance with <u>Section 6.5</u> (Collaboration Program Asset Size Determination), then <font style="font-weight: bold;">[***] </font>the milestone
        payments under <u>Section 6.7</u> (Post-Option Development Milestone Payments), Biogen will pay to Ionis the milestone payments as set forth below when a Post-Option Development Milestone Event listed below is first achieved by Biogen, or its
        Affiliates or Sublicensees for such Product under the <font style="font-weight: bold;">[***] </font>Collaboration Program:</div>
      <div>&#160;</div>
      <div>
        <table cellspacing="0" cellpadding="0" border="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: #000000;" id="ze681a16ece7d4a5499c8070d9bb8c00f">

            <tr>
              <td style="width: 1%; vertical-align: middle; background-color: rgb(217, 217, 217); border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); border-left: 2px solid rgb(0, 0, 0);" colspan="1">&#160;</td>
              <td style="width: 60%; vertical-align: middle; background-color: rgb(217, 217, 217); border-top: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
                <div style="font-size: 12pt; font-weight: bold;">Post-Option Development Milestone Event</div>
              </td>
              <td style="width: 1%; vertical-align: top; background-color: rgb(217, 217, 217); border-left: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);" colspan="1">&#160;</td>
              <td style="width: 38%; vertical-align: top; background-color: rgb(217, 217, 217); border-right: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
                <div style="font-size: 12pt; font-weight: bold;">Milestone Event Payment for</div>
                <div style="font-size: 12pt; font-weight: bold;"> the first Product from the <font style="font-size: 10pt;">[***] </font></div>
                <div style="font-size: 12pt; font-weight: bold;">Collaboration Program</div>
              </td>
            </tr>
            <tr>
              <td style="width: 1%; vertical-align: middle; border-left: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);" colspan="1">&#160;</td>
              <td style="width: 60%; vertical-align: middle; border-right: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
                <div style="font-weight: bold;">[***]</div>
              </td>
              <td style="width: 1%; vertical-align: middle; border-left: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);" colspan="1">&#160;</td>
              <td style="width: 38%; vertical-align: middle; border-right: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
                <div style="text-align: center; font-size: 12pt;">$<font style="font-size: 10pt; font-weight: bold;">[***]</font></div>
              </td>
            </tr>
            <tr>
              <td style="width: 1%; vertical-align: middle; border-left: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);" colspan="1">&#160;</td>
              <td style="width: 60%; vertical-align: middle; border-right: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
                <div style="font-weight: bold;">[***]</div>
              </td>
              <td style="width: 1%; vertical-align: middle; border-left: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);" colspan="1">&#160;</td>
              <td style="width: 38%; vertical-align: middle; border-right: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
                <div style="text-align: center; font-size: 12pt;">$<font style="font-size: 10pt; font-weight: bold;">[***]</font></div>
              </td>
            </tr>
            <tr>
              <td style="width: 1%; vertical-align: middle; border-left: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);" colspan="1">&#160;</td>
              <td style="width: 60%; vertical-align: middle; border-right: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
                <div style="font-weight: bold;">[***]</div>
              </td>
              <td style="width: 1%; vertical-align: middle; border-left: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);" colspan="1">&#160;</td>
              <td style="width: 38%; vertical-align: middle; border-right: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
                <div style="text-align: center; font-size: 12pt;">$<font style="font-size: 10pt; font-weight: bold;">[***]</font></div>
              </td>
            </tr>

        </table>
      </div>
      <div>&#160;</div>
      <div style="text-align: justify; text-indent: 18pt;">9.&#160;&#160;&#160; <font style="font-weight: bold;"><u>[***] Post-Option Development Milestone Payments</u></font>.&#160; If a Product under the <font style="font-weight: bold;">[***]</font> Collaboration Program
        is classified as a <font style="font-weight: bold;">[***] </font>under the Agreement in accordance with <u>Section 6.5</u> (Collaboration Program Asset Size Determination), then <font style="font-weight: bold;">[***] </font>the milestone
        payments under <u>Section 6.7</u> (Post-Option Development Milestone Payments), Biogen will pay to Ionis the milestone payments as set forth below when a Post-Option Development Milestone Event listed below is first achieved by Biogen, its
        Affiliates or Sublicensees for such Product under the <font style="font-weight: bold;">[***] </font>Collaboration Program:</div>
      <div>&#160;</div>
      <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" id="DSPFPageBreakArea">
        <div style="page-break-after:always;" id="DSPFPageBreak">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: #000000;" id="z92d4fa99724e400aba0c23123236da74">

          <tr>
            <td style="width: 1%; vertical-align: middle; background-color: rgb(217, 217, 217); border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); border-left: 2px solid rgb(0, 0, 0);" colspan="1">&#160;</td>
            <td style="width: 60%; vertical-align: middle; background-color: rgb(217, 217, 217); border-top: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
              <div style="font-size: 12pt; font-weight: bold;">Post-Option Development Milestone Event</div>
            </td>
            <td style="width: 1%; vertical-align: top; background-color: rgb(217, 217, 217); border-left: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);" colspan="1">&#160;</td>
            <td style="width: 38%; vertical-align: top; background-color: rgb(217, 217, 217); border-right: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
              <div style="font-size: 12pt; font-weight: bold;">Milestone Event Payment for </div>
              <div style="font-size: 12pt; font-weight: bold;">the first Product from the <font style="font-size: 10pt;">[***]</font> </div>
              <div style="font-size: 12pt; font-weight: bold;">Collaboration Program</div>
            </td>
          </tr>
          <tr>
            <td style="width: 1%; vertical-align: middle; border-left: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);" colspan="1">&#160;</td>
            <td style="width: 60%; vertical-align: middle; border-right: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
              <div style="font-weight: bold;">[***]</div>
            </td>
            <td style="width: 1%; vertical-align: middle; border-left: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);" colspan="1">&#160;</td>
            <td style="width: 38%; vertical-align: middle; border-right: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
              <div style="text-align: center; font-size: 12pt;">$<font style="font-size: 10pt; font-weight: bold;">[***]</font></div>
            </td>
          </tr>
          <tr>
            <td style="width: 1%; vertical-align: middle; border-left: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);" colspan="1">&#160;</td>
            <td style="width: 60%; vertical-align: middle; border-right: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
              <div style="font-weight: bold;">[***]</div>
            </td>
            <td style="width: 1%; vertical-align: middle; border-left: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);" colspan="1">&#160;</td>
            <td style="width: 38%; vertical-align: middle; border-right: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
              <div style="text-align: center; font-size: 12pt;">$<font style="font-size: 10pt; font-weight: bold;">[***]</font></div>
            </td>
          </tr>
          <tr>
            <td style="width: 1%; vertical-align: middle; border-left: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);" colspan="1">&#160;</td>
            <td style="width: 60%; vertical-align: middle; border-right: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
              <div style="font-weight: bold;">[***]</div>
            </td>
            <td style="width: 1%; vertical-align: middle; border-left: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);" colspan="1">&#160;</td>
            <td style="width: 38%; vertical-align: middle; border-right: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
              <div style="text-align: center; font-size: 12pt;">$<font style="font-size: 10pt; font-weight: bold;">[***]</font></div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <div style="text-align: justify; text-indent: 18pt;"><a name="z_Ref60314300"></a>10.&#160; <font style="font-weight: bold;"><u>Ownership of [***] and [***]</u></font>.&#160; Notwithstanding any provision to the contrary set forth in the Agreement, the Parties
        agree that:</div>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z854dbd357ef14e7d9396e56dfee9b077">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 18pt; vertical-align: top; align: right;">a.</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>as between the Parties, Biogen is the sole owner of all rights, title, and interests in and to the Biogen <font style="font-weight: bold;">[***]</font>, and the Biogen <font style="font-weight: bold;">[***]</font> will be considered
                Biogen <font style="font-weight: bold;">[***]</font> (and will not be considered <font style="font-weight: bold;">[***]</font>, <font style="font-weight: bold;">[***]</font>, or <font style="font-weight: bold;">[***]</font>);</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="ze321a3d0ba1e4d4f821525c5c8112d12">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 18pt; vertical-align: top; align: right;">b.</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>all Patent Rights Controlled by Biogen directed to or claiming the Biogen <font style="font-weight: bold;">[***]</font> as a composition of matter in a manner acceptable to a recognized patent office (<font style="font-style: italic;">e.g.</font>,
                the&#160; United States Patent and Trademark Office, the European Patent Office, etc.), including by structure or sequence (the &#8220;<font style="font-weight: bold; font-style: italic;">Biogen</font>&#160;<font style="font-weight: bold;">[***] </font><font style="font-weight: bold; font-style: italic;">Patents</font>&#8221;), will be solely owned by Biogen and will be considered Biogen <font style="font-weight: bold;">[***]</font> with respect to the <font style="font-weight: bold;">[***]</font>
                Collaboration Program (and will not be considered <font style="font-weight: bold;">[***]</font>).&#160; For clarity, Patent Rights that are not Biogen <font style="font-weight: bold;">[***]</font> Patent Rights will not be considered Biogen <font style="font-weight: bold;">[***]</font>, including Patent Rights solely directed to or solely claiming (i) <font style="font-weight: bold;">[***]</font> of Biogen <font style="font-weight: bold;">[***]</font> or (ii) <font style="font-weight: bold;">[***]</font> Biogen <font style="font-weight: bold;">[***]</font>, and such Patent Rights will continue to be Biogen <font style="font-weight: bold;">[***]</font>, <font style="font-weight: bold;">[***] </font>or

                <font style="font-weight: bold;">[***]</font>, <a name="z_cp_text_1_13"></a>as applicable; and</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z9817ddd10e6f45bfb3b3f4d67cf9dc9b">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 18pt; vertical-align: top; align: right;">c.</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>without limiting Paragraph 10(a) of this letter agreement, all Know-How that was discovered, developed, invented or created by or on behalf of either Party or its Affiliates under the Agreement or this letter agreement that <font style="font-weight: bold;">[***]</font> Biogen <font style="font-weight: bold;">[***]</font> will be considered <font style="font-weight: bold;">[***]</font> (as applicable).</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <div style="text-align: justify; text-indent: 18pt;"><a name="z_cp_blt_1_15"></a><a name="z_cp_text_1_16"></a>11.&#160; <font style="font-weight: bold;"><u>Biogen [***] Patent License</u></font>.&#160; Subject to the terms and conditions of the Agreement
        (including Ionis&#8217; exclusivity covenants under <u>Section 2.1.1</u> (Exclusivity Covenants)), Biogen hereby grants Ionis an irrevocable, perpetual, worldwide non-exclusive, sublicensable (subject to the restrictions set forth in <u>Section
          4.3.4(c)</u>), royalty-free license under any Biogen <font style="font-weight: bold;">[***]</font> Patent Controlled by Biogen or its Affiliates at any time during the Agreement Term to research, develop, manufacture, have manufactured and
        commercialize any:</div>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zfedc518275824083bc7d61abbed6eba9">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 18pt; vertical-align: top; align: right;">a.</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>products that include an Oligonucleotide as an active pharmaceutical ingredient (other than products that (i) include an Oligonucleotide that is designed to bind to the RNA that encodes the same target as a product that is being
                developed or commercialized by Biogen, its Affiliates or Sublicensee pursuant to an Option or exclusive license granted from Ionis under this Agreement or any Ionis/Biogen Additional Agreement or (ii) incorporate any Biogen <font style="font-weight: bold;">[***]</font>); and</div>
            </td>
          </tr>

      </table>
      <div> <br>
      </div>
      <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" id="DSPFPageBreakArea">
        <div style="page-break-after:always;" id="DSPFPageBreak">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z47e69cc55d9b455e9df01462178299c7">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 18pt; vertical-align: top; align: right;">b.</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>Gene-Editing Products that do not incorporate any Biogen <font style="font-weight: bold;">[***]</font>.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <div style="text-align: justify; text-indent: 18pt;">12.&#160; <font style="font-weight: bold;"><u>Third Party Obligations for [***]</u></font>.&#160; Notwithstanding <u>Section 6.11</u> (Third Party Rights and Payment Obligations), so long as Biogen has an
        Option with respect to the <font style="font-weight: bold;">[***]</font> Strategy or a license under <u>Section 4.1</u> (License Grants to Biogen) with respect to the <font style="font-weight: bold;">[***]</font> Collaboration Program, <font style="font-weight: bold;">[***]</font> will have the sole right and discretion, at its sole cost and expense, to acquire rights (whether by purchase, assignment, license, or otherwise) or other access to Patent Rights that are <font style="font-weight: bold;">[***]</font> the Biogen <font style="font-weight: bold;">[***]</font> that is incorporated into any Product under the <font style="font-weight: bold;">[***] </font>Collaboration Program and <font style="font-weight: bold;">[***]</font> will have no right of offset under <u>Section 6.11</u> (Third Party Rights and Payment Obligations) for such Product Specific Payments, <font style="font-style: italic;">provided</font>, <font style="font-style: italic;">however</font>,
        the foregoing will not apply to any payments and other obligations to Third Parties to acquire rights (whether by purchase, assignment, license, or otherwise) or other access to Patent Rights that <a name="z_cp_text_1_18"></a>are <font style="font-weight: bold;">[***]</font> (a) <font style="font-weight: bold;">[***]</font> any Biogen <font style="font-weight: bold;">[***]</font>, or (b) <font style="font-weight: bold;">[***]</font> any Biogen <font style="font-weight: bold;">[***]</font> (and such Product-Specific Payments, in each case ((a) and (b)), will remain subject to the terms of <u>Article 6</u> (Financial Provisions), to the extent applicable).</div>
      <div>&#160;</div>
      <div style="text-align: justify; text-indent: 18pt;"><a name="z_Ref60314229"></a>13.&#160;&#160; <font style="font-weight: bold;"><u>Prosecution and Maintenance, Defense, and Enforcement of Patents</u></font>.</div>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z68d823c63e3a47bb9e30b57430819cbd">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 18pt; vertical-align: top; align: right;">a.</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Prosecution and Maintenance</font>.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zd797951404b24733a9d5413e87cc3a31">

          <tr>
            <td style="width: 99pt;"><br>
            </td>
            <td style="width: 18pt; vertical-align: top;">i.</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-style: italic;">Prosecution and Maintenance of Biogen </font><font style="font-weight: bold;">[***]</font>&#160;<font style="font-style: italic;">Patents</font>.&#160; Notwithstanding any provision to the contrary set forth in <u>Section

                  7.2</u> (Prosecution and Maintenance of Patents), Biogen will control and be responsible for all aspects of the Prosecution and Maintenance of all Biogen <font style="font-weight: bold;">[***]</font> Patents.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zb03445ade3ff43b982f3b6f7a532ccb0">

          <tr>
            <td style="width: 99pt;"><br>
            </td>
            <td style="width: 18pt; vertical-align: top;">ii.</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-style: italic;">Prosecution and Maintenance of Biogen </font><font style="font-weight: bold;">[***] </font><font style="font-style: italic;">Patents</font>.&#160; Prosecution and Maintenance of all Patent Rights that claim
                any Biogen <font style="font-weight: bold;">[***]</font> (the &#8220;<font style="font-weight: bold; font-style: italic;">Biogen </font><font style="font-weight: bold;">[***]</font><font style="font-weight: bold; font-style: italic;"> Patents</font>&#8221;)

                will be subject to the terms of <u>Section 7.2</u> (Prosecution and Maintenance of Patents), to the extent applicable; <font style="font-style: italic;">provided</font>, <font style="font-style: italic;">however</font>, that
                notwithstanding any provision to the contrary set forth in <u>Section 7.2.5</u> (Other Matters Pertaining to Prosecution and Maintenance of Patents) if (A) Ionis has the responsibility to Prosecute and Maintain any Biogen <font style="font-weight: bold;">[***]</font> Patents pursuant to <u>Section 7.2</u> (Prosecution and Maintenance of Patents), (B) Biogen timely provides any comments with respect to any draft filing, communication, response, or strategy with
                respect to such Patent Rights in accordance with <u>Section 7.2.5</u> (Other Matters Pertaining to Prosecution and Maintenance of Patents), and (C) Ionis decides not to incorporate any such comment timely provided by Biogen, then Biogen
                may refer the matter to Expert Resolution for resolution under <u>Section 12.1.4</u> (Expert Resolution). If Biogen terminates the <font style="font-weight: bold;">[***]</font> Collaboration Program as described in Paragraph 14 or 15 of
                this letter agreement, then the terms of&#160; <u>Section 7.2</u> (Prosecution and Maintenance of Patents) and this Paragraph 13(a)(ii) will survive such termination solely with respect to the Prosecution and Maintenance of the Biogen <font style="font-weight: bold;">[***]</font> Patents.</div>
            </td>
          </tr>

      </table>
      <div> <br>
      </div>
      <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" id="DSPFPageBreakArea">
        <div style="page-break-after:always;" id="DSPFPageBreak">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zb8bf508e55de44bdac91531a4190e84d">

          <tr>
            <td style="width: 99pt;"><br>
            </td>
            <td style="width: 18pt; vertical-align: top;">iii.</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-style: italic;">Coordination</font>.&#160; Notwithstanding Biogen&#8217;s right to Prosecute and Maintain the Biogen <font style="font-weight: bold;">[***]</font> Patents or each Party&#8217;s right to Prosecute and Maintain the Biogen
                <font style="font-weight: bold;">[***]</font> Patents to the extent provided in <u>Section 7.2</u> (Prosecution and Maintenance of Patents) and this letter agreement, the Parties will, and will cause their Affiliates to, cooperate and
                implement reasonable patent filing and prosecution strategies (including filing divisionals, continuations or otherwise) to ensure that, to the extent reasonable and feasible, Patent Rights claiming the Biogen <font style="font-weight: bold;">[***]</font> and Patent Rights claiming any <font style="font-weight: bold;">[***]</font> directed to <font style="font-weight: bold;">[***]</font> under the <font style="font-weight: bold;">[***] </font>Collaboration Program
                are pursued in a manner that are not detrimental to each such set of Patent Rights.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z7bbacd69b9434c999c93a376af7245d2">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 18pt; vertical-align: top; align: right;">b.</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;">Enforcement</font>.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z602917d42af64bfa8680104e7d5950b7">

          <tr>
            <td style="width: 99pt;"><br>
            </td>
            <td style="width: 18pt; vertical-align: top;">i.</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-style: italic;">Enforcement of Biogen </font><font style="font-weight: bold;">[***]</font>&#160;<font style="font-style: italic;">Patents</font>.&#160; Notwithstanding any provision to the contrary set forth in <u>Section 7.5</u>
                (Enforcement of Patents against Competitive Infringement), for any Competitive Infringement with respect to a Product to the extent involving any Biogen <font style="font-weight: bold;">[***]</font> Patent, Biogen will have the sole right,
                but not the obligation, to institute, prosecute, and control any Proceeding with respect thereto by counsel of its own choice at its own expense.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zf7362fbf32e048cf9c74224686c27d0d">

          <tr>
            <td style="width: 99pt;"><br>
            </td>
            <td style="width: 18pt; vertical-align: top;">ii.</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-style: italic;">Enforcement of Biogen </font><font style="font-weight: bold;">[***]</font><font style="font-style: italic;"> Patents</font>.&#160; Any Competitive Infringement with respect to a Product to the extent
                involving any Biogen <font style="font-weight: bold;">[***]</font> Patent will be subject to the terms of <u>Section 7.5</u> (Enforcement of Patents against Competitive Infringement); <font style="font-style: italic;">provided</font>, <font style="font-style: italic;">however</font>, that notwithstanding any provision to the contrary set forth in <u>Section 7.5</u> (Enforcement of Patents against Competitive Infringement), if (A) Ionis has the right to institute, prosecute,
                and control any Proceeding to the extent involving any such Biogen <font style="font-weight: bold;">[***]</font> Patent pursuant to <u>Section 7.5</u> (Enforcement of Patents against Competitive Infringement), (B) Biogen timely provides
                any comments with respect to filings, submissions and communications related to such Proceeding in accordance with <u>Section 7.5</u> (Enforcement of Patents against Competitive Infringement), and (C) Ionis decides not to incorporate any
                such comment timely provided by Biogen, then Biogen may refer the matter to Expert Resolution for resolution under <u>Section 12.1.4</u> (Expert Resolution).</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <div style="text-align: justify; text-indent: 18pt;"><a name="z_Ref60314201"></a>14.&#160; <font style="font-weight: bold;"><u>Consequences of Termination or Failure to Designate a Development Candidate Prior to License Effective Date</u></font>.&#160; If (A)
        the Agreement with respect to the <font style="font-weight: bold;">[***]</font> Collaboration Program or the <font style="font-weight: bold;">[***] </font>Collaboration Program is terminated by Biogen pursuant to <u>Section 10.3.2</u> (Biogen&#8217;s
        Termination for Convenience) before the License Effective Date for such Collaboration Program or the Option with respect to such Collaboration Program expires unexercised, (B) Biogen has not reasonably determined (and Biogen has not so notified
        Ionis in writing of such determination and the rationale therefor, which such notice must be delivered (I) in the event Biogen so terminates such Collaboration Program, then together with such notice of termination, or (II) in the event the Option
        with respect to such Collaboration Program expires unexercised, then prior to the expiration of the Option (each of (I) and (II), the &#8220;<font style="font-weight: bold;">Reversion</font>&#160;<font style="font-weight: bold;">Notification Deadline</font>&#8221;))

        that any further Research, Development, Manufacture, and Commercialization of Terminated Strategy Products that are the subject of such Collaboration Program <font style="font-weight: bold;">[***]</font> (subject to Paragraph 16 of this letter
        agreement), and (C) such termination of the Agreement is not due to <font style="font-weight: bold;">[***]</font> that are reasonably demonstrated by Biogen to Ionis on or prior to the applicable Reversion Notification Deadline, then, in addition
        to the terms set forth in <u>Section 10.6.1</u> (In General), the following terms will apply:</div>
      <div style="text-align: justify; text-indent: 18pt;"> <br>
      </div>
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        <div style="page-break-after:always;" id="DSPFPageBreak">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zc641f0326f1948aa9167b7cbbac76604">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 18pt; vertical-align: top; align: right;">a.</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>Biogen&#8217;s Option under <u>Section 3.1</u> (Option) will expire with respect to such Collaboration Program;</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z2102e583bb65427ea9cb517b2f7ca137">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 18pt; vertical-align: top; align: right;">b.</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>Notwithstanding anything to the contrary set forth in <u>Section 2.1.1</u> (Exclusivity Covenants) and regardless of whether Biogen has exercised an Option for another Collaboration Program directed to <font style="font-weight: bold;">[***]</font>,
                Ionis will be free to Develop, Manufacture and Commercialize Terminated Strategy Product(s) with respect to such Collaboration Program, on its own or with a Third Party, <font style="font-style: italic;">provided</font>, <font style="font-style: italic;">however</font>, that Ionis will not, on its own or with any Third Party, change, use an alternate, or in any way modify, any Terminated Strategy Product, including any Biogen <font style="font-weight: bold;">[***]</font>
                included therein, that is incorporated into any Terminated Strategy Product, except for any Permitted Changes in&#160; Form.&#160; For clarity, the terms of <u>Section 2.1.1</u> (Exclusivity Covenants) will continue to govern the Development and
                Commercialization by Ionis or its Affiliates of any Products directed to <font style="font-weight: bold;">[***]</font> that are not Terminated Strategy Products, to the extent applicable.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zedf7290098fc42f0ac0873a8f8871895">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 18pt; vertical-align: top; align: right;"><a name="z_Ref59313227"></a>c.</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>To the extent requested by Ionis, Biogen will promptly transfer to Ionis all data, results, and information (including Biogen&#8217;s Confidential Information and any regulatory documentation (including drafts)) related to the testing and
                Clinical Studies for such Terminated Strategy Products in the possession of Biogen or its contractors, to the extent such data, results, and information were generated by or on behalf of Biogen under the Agreement; and Ionis will pay all
                out-of-pocket direct Third Party costs and expenses in transferring such data, results and information together with the Biogen FTE Cost in transferring such data, results and information.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zbe3af059ab484c24a6e0f5e76f8d399a">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 18pt; vertical-align: top; align: right;">d.</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div>The provisions of <u>Section 10.6.3(h)</u> will apply solely with respect to such Terminated Strategy Products (and for clarity, not with respect to other Discontinued Products that are the subject of such Collaboration Program), <font style="font-style: italic;">mutatis mutandis</font>, and solely for the purposes of <u>Section 10.6.3(h)</u>, <font style="font-weight: bold;">[***]</font> will be considered a Terminated Target thereunder, <font style="font-style: italic;">provided</font>, <font style="font-style: italic;">however</font>, that the terms of <u>Section 10.6.3(h)(v)</u> will not apply to, and Biogen will not be required to provide to Ionis, any Regulatory Materials that solely
                relate to the Biogen <font style="font-weight: bold;">[***] </font>incorporated into the Terminated Strategy Product, unless requested by a Regulatory Authority, in which case Biogen will provide such information to Ionis, <a name="z_cp_text_1_24"></a>solely for the purposes of submitting such information to such Regulatory Authority, subject to <u>Article 11</u> (Confidentiality).</div>
            </td>
          </tr>

      </table>
      <div> <br>
      </div>
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          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
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              <div>For the purposes of this letter agreement, &#8220;<font style="font-weight: bold; font-style: italic;">Terminated Strategy Products</font>&#8221; means, with respect to the <font style="font-weight: bold;">[***] </font>Collaboration Program or the
                <font style="font-weight: bold;">[***]</font> Collaboration Program (as applicable), all Products that (i) are the subject of such Collaboration Program and that are in existence as of the effective date of termination of the Agreement with
                respect to such Collaboration Program, (ii) only utilize the Strategy of such Collaboration Program (<font style="font-style: italic;">i.e.</font>, as such Strategy is defined in the recitals to this letter agreement), and (iii) are either
                in the form that such Products exist as of such effective date of termination or are any Permitted Changes in Form.</div>
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      <div style="text-align: justify; text-indent: 18pt;"><a name="z_Ref60314209"></a>15.&#160; <font style="font-weight: bold;"><u>Consequences of Termination After License Effective Date</u></font>.&#160; If (A) the Agreement with respect to the <font style="font-weight: bold;">[***]</font> Collaboration Program or the <font style="font-weight: bold;">[***]</font> Collaboration Program is terminated by Biogen under <u>Section 10.3.2</u> (Biogen&#8217;s Termination for Convenience) after the
        License Effective Date for such Collaboration Program, (B) Biogen has not reasonably determined (and Biogen has not so notified Ionis in writing of such determination and the rationale therefor, which such notice must be delivered on or prior to
        the applicable Reversion Notification Deadline) that any further Research, Development, Manufacture, and Commercialization of Terminated Strategy Products that are the subject of such Collaboration Program <font style="font-weight: bold;">[***]</font>
        (subject to Paragraph 16 of this letter agreement), and (C) such termination of the Agreement is not due to <font style="font-weight: bold;">[***]</font> that are reasonably demonstrated by Biogen to Ionis on or prior to the applicable Reversion
        Notification Deadline, then, in addition to the terms set forth in <u>Section 10.6.1</u> (In General), the following terms will apply:</div>
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              <div>The applicable licenses granted by Ionis to Biogen under the Agreement will terminate with respect to such Collaboration Program.&#160; Biogen, its Affiliates and Sublicensees will cease selling the Products that are the subject of such
                Collaboration Program, unless Ionis elects to have Biogen continue to sell such Products as part of the Transition Services to the extent provided in <u>Section 10.6.6</u> (Transition Services).</div>
            </td>
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      <div>&#160;</div>
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              <div>Notwithstanding anything to the contrary set forth in <u>Section 2.1.1</u> (Exclusivity Covenants) and regardless of whether Biogen has exercised an Option for another Collaboration Program directed to <font style="font-weight: bold;">[***]</font>,
                Ionis will be free to Develop, Manufacture and Commercialize Terminated Strategy Product(s) with respect to such Collaboration Program, on its own or with a Third Party, <font style="font-style: italic;">provided</font>, <font style="font-style: italic;">however</font>, that Ionis will not, on its own or with any Third Party, change, use an alternate, or in any way modify, any Terminated Strategy Product, including any Biogen <font style="font-weight: bold;">[***]</font>
                included therein, that is incorporated into any Terminated Strategy Product, except for any Permitted Changes in Form.&#160; For clarity, the terms of <u>Section 2.1.1</u> (Exclusivity Covenants) will continue to govern the Development and
                Commercialization by Ionis or its Affiliates of any Products directed to <font style="font-weight: bold;">[***]</font> that are not Terminated Strategy Products, to the extent applicable.</div>
            </td>
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      <div> <br>
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      <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" id="DSPFPageBreakArea">
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            <td style="width: 18pt; vertical-align: top; align: right;">c.</td>
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              <div>The provisions of <u>Section 10.6.4(d)</u>, <u>Section 10.6.4(e)</u> and <u>Section 10.6.4(f)</u> will apply solely with respect to such Terminated Strategy Products (and for clarity, not with respect to other Discontinued Products
                that are the subject of such Collaboration Program), <font style="font-style: italic;">mutatis mutandis</font>, and solely for the purposes of <u>Section 10.6.4(d)</u>, <u>Section 10.6.4(e)</u> and <u>Section 10.6.4(f)</u>, <font style="font-weight: bold;">[***]</font> will be considered a Terminated Target thereunder, <font style="font-style: italic;">provided</font>, <font style="font-style: italic;">however</font>, that (i) for the purposes of <u>Section
                  10.6.4(f)</u>, to the extent requested by Ionis, Biogen will only be required to assign to Ionis any manufacturing agreements to the extent solely related to the Terminated Strategy Products (and, for clarity, will not be obligated to
                assign to Ionis any manufacturing agreements that relate to <font style="font-weight: bold;">[***]</font> generally), (ii) following the assignment back by Biogen to Ionis of the Product-Specific Patents described in <u>Section
                  10.6.4(d)(v)</u>, Ionis will and hereby does grant to Biogen a worldwide, non-exclusive, sublicensable license under such Patent Rights to research, Develop, Manufacture, have Manufactured, register, market, and Commercialize any Biogen <font style="font-weight: bold;">[***]</font>, whether alone or in combination with any other compound or conjugate, but excluding Terminated Strategy Products, and (iii) the terms of <u>Section 10.6.4(d)(ix)</u> will not apply to the
                Prosecution and Maintenance of any Biogen <font style="font-weight: bold;">[***]</font> Patents (and for clarity, the terms of Paragraph 13(a)(ii) of this letter agreement will apply to the Prosecution and Maintenance of such Patent
                Rights).</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z6ec13d4fd8394c618e4ba33b67fe0d14">

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            <td style="width: 18pt;"><br>
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            <td style="width: 18pt; vertical-align: top; align: right;"><a name="z_Ref60314241"></a>16.</td>
            <td style="width: auto; vertical-align: top; text-align: justify;">
              <div><font style="font-weight: bold;"><u>Disputes Regarding Biogen Notification of [***] Terminated Strategy Products</u></font>.&#160; If Ionis disputes Biogen&#8217;s determination under clause (B) of Paragraph 14 or clause (B) of Paragraph 15 of this
                letter agreement that any further Research, Development, Manufacture, and Commercialization of Terminated Strategy Products that are the subject of a terminated <font style="font-weight: bold;">[***]</font> Collaboration Program <font style="font-weight: bold;">[***]</font>, then Ionis may refer the matter to Expert Resolution for resolution under <u>Section 12.1.4</u> (Expert Resolution).</div>
            </td>
          </tr>

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      <div>&#160;</div>
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          <tr>
            <td style="width: 18pt;"><br>
            </td>
            <td style="width: 18pt; vertical-align: top; align: right;">17.</td>
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              <div><font style="font-weight: bold;"><u>Publications Prior to License Effective Date</u></font>.&#160; Notwithstanding any provision to the contrary set forth in <u>Section 11.4</u> (Press Release; Publications; Disclosure of Agreement):</div>
            </td>
          </tr>

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      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z5dbc74229e574690b497e40b2b02246b">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 18pt; vertical-align: top; align: right;">a.</td>
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              <div>Solely with respect to the <font style="font-weight: bold;">[***]</font> Collaboration Program, the terms of <u>Section 11.4.4</u> (Prior to License Effective Date) are hereby amended and replaced with the following: &#8220;prior to the
                License Effective Date for the <font style="font-weight: bold;">[***]</font> Collaboration Program, neither Party will have sole right to issue press releases, publish, present or otherwise disclose the progress and results regarding such
                Products to the public without the prior written consent of the other Party&#8221;; and</div>
            </td>
          </tr>

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      <div>&#160;</div>
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            <td style="width: 54pt;"><br>
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            <td style="width: 18pt; vertical-align: top; align: right;">b.</td>
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              <div>Biogen will have the sole right to issue press releases, publish, present, or otherwise disclose the progress and results regarding the Biogen <font style="font-weight: bold;">[***]</font> if such press release, publication,
                presentation, or other disclosure does not disclose any progress or results regarding any <font style="font-weight: bold;">[***]</font> that is incorporated into any Product under the <font style="font-weight: bold;">[***] </font>Collaboration

                Program.</div>
            </td>
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      <div style="text-align: justify; text-indent: 36pt;">The terms of <u>Section 12.14</u> (Interpretation) will govern the terms of this letter agreement.&#160; Except as otherwise expressly set forth herein, the provisions of the Agreement will remain in
        full force and effect and each Party reserves its rights thereunder.&#160; In the event of any express conflict or inconsistency between this letter agreement and the Agreement, the terms of this letter agreement will apply.</div>
      <div style="text-align: justify; text-indent: 36pt;"> <br>
      </div>
      <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" id="DSPFPageBreakArea">
        <div style="page-break-after:always;" id="DSPFPageBreak">
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      </div>
      <div style="text-align: justify; text-indent: 36pt;">If you accept the terms and conditions set forth in this letter agreement, please so indicate by executing a copy of this letter agreement and returning it to Ionis. This letter agreement may be
        executed in counterparts, each of which will be deemed an original, notwithstanding variations in format or file designation which may result from electronic transmission, store and printing of copies of this letter agreement from separate
        computers or printers. Facsimile signatures and signatures transmitted via electronic mail in PDF format will be treated as original signatures.</div>
      <div><br>
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      <div style="text-align: center;">[<font style="font-style: italic;">SIGNATURE</font>&#160;<font style="font-style: italic;">PAGE FOLLOWS</font>]</div>
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          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
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          <tr>
            <td style="width: 50%; vertical-align: top;">&#160;</td>
            <td style="width: 50%; vertical-align: top;">
              <div>Sincerely,</div>
            </td>
          </tr>
          <tr>
            <td style="width: 50%; vertical-align: top;">&#160;</td>
            <td style="width: 50%; vertical-align: top;">&#160;</td>
          </tr>
          <tr>
            <td style="width: 50%; vertical-align: top;">&#160;</td>
            <td style="width: 50%; vertical-align: top;">
              <div><u>/s/Brett Monia</u></div>
            </td>
          </tr>
          <tr>
            <td style="width: 50%; vertical-align: top;">&#160;</td>
            <td style="width: 50%; vertical-align: top;">
              <div>Brett Monia</div>
            </td>
          </tr>
          <tr>
            <td style="width: 50%; vertical-align: top;">&#160;</td>
            <td style="width: 50%; vertical-align: top;">
              <div>Chief Executive Officer</div>
            </td>
          </tr>
          <tr>
            <td style="width: 50%; vertical-align: top;">&#160;</td>
            <td style="width: 50%; vertical-align: top;">
              <div>Ionis Pharmaceuticals, Inc.</div>
            </td>
          </tr>

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      <div><br>
      </div>
      <div>AGREED AND CONFIRMED ON BEHALF OF BIOGEN MA INC.:</div>
      <div>&#160;</div>
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          <tr>
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              <div>By:</div>
            </td>
            <td style="width: 95%; vertical-align: top;">
              <div><u>/s/Anabella Villalobos</u></div>
            </td>
          </tr>
          <tr>
            <td style="width: 5%; vertical-align: top;">
              <div>Name:</div>
            </td>
            <td style="width: 95%; vertical-align: top;">
              <div>Anabella Villalobos</div>
            </td>
          </tr>
          <tr>
            <td style="width: 5%; vertical-align: top;">
              <div>Title:</div>
            </td>
            <td style="width: 95%; vertical-align: top;">
              <div>Senior Vice President, Biotherapeutics &amp; Medicinal Sciences</div>
            </td>
          </tr>
          <tr>
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              <div>Date:</div>
            </td>
            <td style="width: 95%; vertical-align: top;">
              <div>December 31, 2020</div>
            </td>
          </tr>

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      <div><br>
      </div>
      <div>&#160;</div>
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<DOCUMENT>
<TYPE>EX-21.1
<SEQUENCE>9
<FILENAME>exhibit21_1.htm
<DESCRIPTION>EXHIBIT 21.1
<TEXT>
<html><head>
    <title>&nbsp;</title>
    <!-- Licensed to: Ionis
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         Copyright 1995 - 2021 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 France SAS, a French Company</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; color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Akcea Securities Corporation., a Massachusetts Corporation</div><div><br></div><div style="text-align: left; color: #000000; font-family: 'Times New Roman', 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;">Isis 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;">PerIsis I Development Corporation, a Delaware Corporation</div><div><br></div><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Symphony GenIsis,&#160;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></body></html>
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<DOCUMENT>
<TYPE>EX-23.1
<SEQUENCE>10
<FILENAME>exhibit23_1.htm
<DESCRIPTION>EXHIBIT 23.1
<TEXT>
<html>
  <head>
    <title>&#160;</title>
    <!-- Licensed to: Ionis
         Document created using EDGARfilings PROfile 7.3.2.0
         Copyright 1995 - 2021 Broadridge -->
  </head>
<body style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">
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    <div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Exhibit&#160;23.1</div>
    <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">&#160;</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&#160;S-3 (Nos.&#160;333-71911, 333-90811, 333-38844, 333-71116, 333-71176,
      333-89066, 333-89626, 333-128156, 333-130639, 333-134380, 333-141447, 333-151076 and 333-188407) and in the related Prospectuses, as applicable, and in the Registration Statements on Form&#160;S-8 (Nos.333-05825, 333-55683, 333-40336, 333-91572,
      333-106859, 333-116962, 333-125911, 333-133853, 333-142777, 333-151996, 333-160269, 333-168674, 333-176136, 333-184788, 333-190408 and 333-207900) of Ionis Pharmaceuticals,&#160;Inc. of our reports dated February 24, 2021, with respect to the consolidated
      financial statements of Ionis Pharmaceuticals,&#160;Inc. and the effectiveness of internal control over financial reporting of Ionis Pharmaceuticals,&#160;Inc. included in this Annual Report (Form&#160;10-K) for the year ended December&#160;31, 2020.</div>
    <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#160;</div>
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            <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">/s/ ERNST&#160;&amp; YOUNG LLP</div>
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          <td style="width: 50.57%; vertical-align: top;">
            <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#160;</div>
          </td>
          <td style="width: 49.43%; vertical-align: top;">
            <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#160;</div>
          </td>
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          <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>
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          <td style="width: 49.43%; vertical-align: top;">
            <div style="text-align: left; font-family: 'Times New Roman'; font-size: 1pt;">&#160;</div>
          </td>
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          <td style="width: 50.57%; vertical-align: top;">
            <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">February 24, 2021</div>
          </td>
          <td style="width: 49.43%; vertical-align: top;">
            <div style="text-align: left; font-family: 'Times New Roman'; font-size: 1pt;">&#160;</div>
          </td>
        </tr>

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    <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#160;</div>
  </div>
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</TEXT>
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<DOCUMENT>
<TYPE>EX-31.1
<SEQUENCE>11
<FILENAME>exhibit31_1.htm
<DESCRIPTION>EXHIBIT 31.1
<TEXT>
<html><head>
    <title>&nbsp;</title>
    <!-- Licensed to: Ionis
         Document created using EDGARfilings PROfile 7.3.2.0
         Copyright 1995 - 2021 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; color: #000000; 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; color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">CERTIFICATION</div><div><br></div><div style="text-align: justify; color: #000000; 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="z8a0949f2fcc347f48dc1b00b0124f695"><tr><td style="width: 27pt; vertical-align: top; align: right;"><div style="text-align: left; margin-left: 9pt; color: #000000; 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; color: #000000; 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="z4701978a37d346ec9c67f5acfcb03c7a"><tr><td style="width: 27pt; vertical-align: top; align: right;"><div style="text-align: left; margin-left: 9pt; color: #000000; 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; color: #000000; 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="za477dc30a91948328c767bcca3657233"><tr><td style="width: 27pt; vertical-align: top; align: right;"><div style="text-align: left; margin-left: 9pt; color: #000000; 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; color: #000000; 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="zc6d673ade1f24943a7f5623c6e56f8c0"><tr><td style="width: 27pt; vertical-align: top; align: right;"><div style="text-align: left; margin-left: 9pt; color: #000000; 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; color: #000000; 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="z2da3dbe75a194de3b07c93afb0f8da08"><tr><td style="width: 45pt; vertical-align: top; align: right;"><div style="text-align: left; margin-left: 27pt; color: #000000; 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; color: #000000; 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="z874f7bb1584641d6968b51674a9f53c6"><tr><td style="width: 45pt; vertical-align: top; align: right;"><div style="text-align: left; margin-left: 27pt; color: #000000; 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; color: #000000; 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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="z6341256221b74e618df8f0d9a7fa12de"><tr><td style="width: 45pt; vertical-align: top; align: right;"><div style="text-align: left; margin-left: 27pt; color: #000000; 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; color: #000000; 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; 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vertical-align: top; align: right;"><div style="text-align: left; margin-left: 27pt; color: #000000; 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; color: #000000; 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; color: #000000; 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="z157bc8e642324e47b190dc80daffdabe"><tr><td style="width: 41.41%; vertical-align: top;"><div style="text-align: left; color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Dated: February 24, 2021</div></td><td style="width: 58.59%; vertical-align: top;"><div style="text-align: left; color: #000000; 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; color: #000000; 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; color: #000000; 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; color: #000000; 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; color: #000000; 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; color: #000000; 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; color: #000000; 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; color: #000000; 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; color: #000000; 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>12
<FILENAME>exhibit31_2.htm
<DESCRIPTION>EXHIBIT 31.2
<TEXT>
<html><head>
    <title>&nbsp;</title>
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  </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; color: #000000; 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; color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">CERTIFICATION</div><div><br></div><div style="text-align: justify; color: #000000; 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="zfbc02ad3393d4387a9fd059be71273e6"><tr><td style="width: 27pt; vertical-align: top; align: right;"><div style="text-align: left; margin-left: 9pt; color: #000000; 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; color: #000000; 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="z9f50afdab8b9425dbc608fea66c99435"><tr><td style="width: 27pt; vertical-align: top; align: right;"><div style="text-align: left; margin-left: 9pt; color: #000000; 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; color: #000000; 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="zdd4384a066754835b846d21f14f0e75b"><tr><td style="width: 27pt; vertical-align: top; align: right;"><div style="text-align: left; margin-left: 9pt; color: #000000; 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; color: #000000; 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="z1f7b817c5c3b4951b19e176c3619647a"><tr><td style="width: 27pt; vertical-align: top; align: right;"><div style="text-align: left; margin-left: 9pt; color: #000000; 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; color: #000000; 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="zeadf79c7c0614d50ab0bb23d4ee0412c"><tr><td style="width: 45pt; vertical-align: top; align: right;"><div style="text-align: left; margin-left: 27pt; color: #000000; 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; color: #000000; 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="zed66ed52be544d989f93caa41ed02074"><tr><td style="width: 45pt; vertical-align: top; align: right;"><div style="text-align: left; margin-left: 27pt; color: #000000; 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; color: #000000; 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="z78bccd7527704f0aaf613be8d14b42c7"><tr><td style="width: 45pt; vertical-align: top; align: right;"><div style="text-align: left; margin-left: 27pt; color: #000000; 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; color: #000000; 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="ze139e715ff3743708b9d6be2831937ab"><tr><td style="width: 45pt; vertical-align: top; align: right;"><div style="text-align: left; margin-left: 27pt; color: #000000; 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; color: #000000; 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; 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vertical-align: top; align: right;"><div style="text-align: left; margin-left: 27pt; color: #000000; 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; color: #000000; 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; color: #000000; 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="ze08b3b893ed84572adaf3c5e2de09c76"><tr><td style="width: 41.23%; vertical-align: top;"><div style="text-align: left; color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Dated: February 24, 2021</div></td><td style="width: 58.77%; vertical-align: top;"><div style="text-align: left; color: #000000; 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; color: #000000; 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; color: #000000; 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; color: #000000; 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; color: #000000; 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; color: #000000; 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; color: #000000; 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; color: #000000; 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; color: #000000; 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>13
<FILENAME>exhibit32_1.htm
<DESCRIPTION>EXHIBIT 32.1
<TEXT>
<html><head>
    <title>&nbsp;</title>
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  </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; color: #000000; 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; color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">CERTIFICATION</div><div><br></div><div style="text-align: justify; text-indent: 36pt; color: #000000; 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. 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        <link:definition>090104 - Disclosure - Organization and Significant Accounting Policies, Revenue Recognition (Details)</link:definition>
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        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
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      <link:roleType roleURI="http://ionispharma.com/role/OrganizationAndSignificantAccountingPoliciesContractsReceivableDetails" id="OrganizationAndSignificantAccountingPoliciesContractsReceivableDetails">
        <!--Parent Role: Organization and Significant Accounting Policies-->
        <link:definition>090106 - Disclosure - Organization and Significant Accounting Policies, Contracts Receivable (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
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      <link:roleType roleURI="http://ionispharma.com/role/OrganizationAndSignificantAccountingPoliciesDeferredRevenueDetails" id="OrganizationAndSignificantAccountingPoliciesDeferredRevenueDetails">
        <!--Parent Role: Organization and Significant Accounting Policies-->
        <link:definition>090108 - Disclosure - Organization and Significant Accounting Policies, Deferred Revenue (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
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      <link:roleType roleURI="http://ionispharma.com/role/OrganizationAndSignificantAccountingPoliciesResearchDevelopmentAndPatentExpensesDetails" id="OrganizationAndSignificantAccountingPoliciesResearchDevelopmentAndPatentExpensesDetails">
        <!--Parent Role: Organization and Significant Accounting Policies-->
        <link:definition>090112 - Disclosure - Organization and Significant Accounting Policies, Research, Development and Patent Expenses (Details)</link:definition>
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        <link:usedOn>link:calculationLink</link:usedOn>
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      <link:roleType roleURI="http://ionispharma.com/role/OrganizationAndSignificantAccountingPoliciesAccruedLiabilitiesDetails" id="OrganizationAndSignificantAccountingPoliciesAccruedLiabilitiesDetails">
        <!--Parent Role: Organization and Significant Accounting Policies-->
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        <link:usedOn>link:calculationLink</link:usedOn>
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      <link:roleType roleURI="http://ionispharma.com/role/OrganizationAndSignificantAccountingPoliciesNoncontrollingInterestInAkceaTherapeuticsIncDetails" id="OrganizationAndSignificantAccountingPoliciesNoncontrollingInterestInAkceaTherapeuticsIncDetails">
        <!--Parent Role: Organization and Significant Accounting Policies-->
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        <link:usedOn>link:presentationLink</link:usedOn>
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        <link:usedOn>link:definitionLink</link:usedOn>
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      <link:roleType roleURI="http://ionispharma.com/role/OrganizationAndSignificantAccountingPoliciesCashCashEquivalentsAndInvestmentsDetails" id="OrganizationAndSignificantAccountingPoliciesCashCashEquivalentsAndInvestmentsDetails">
        <!--Parent Role: Organization and Significant Accounting Policies-->
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        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
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      <link:roleType roleURI="http://ionispharma.com/role/OrganizationAndSignificantAccountingPoliciesInventoryValuationDetails" id="OrganizationAndSignificantAccountingPoliciesInventoryValuationDetails">
        <!--Parent Role: Organization and Significant Accounting Policies-->
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        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
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      <link:roleType roleURI="http://ionispharma.com/role/OrganizationAndSignificantAccountingPoliciesPropertyPlantAndEquipmentDetails" id="OrganizationAndSignificantAccountingPoliciesPropertyPlantAndEquipmentDetails">
        <!--Parent Role: Organization and Significant Accounting Policies-->
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        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
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      <link:roleType roleURI="http://ionispharma.com/role/OrganizationAndSignificantAccountingPoliciesLonglivedAssetsDetails" id="OrganizationAndSignificantAccountingPoliciesLonglivedAssetsDetails">
        <!--Parent Role: Organization and Significant Accounting Policies-->
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        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
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      <link:roleType roleURI="http://ionispharma.com/role/OrganizationAndSignificantAccountingPoliciesStockbasedCompensationExpenseDetails" id="OrganizationAndSignificantAccountingPoliciesStockbasedCompensationExpenseDetails">
        <!--Parent Role: Organization and Significant Accounting Policies-->
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        <link:usedOn>link:calculationLink</link:usedOn>
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      <link:roleType roleURI="http://ionispharma.com/role/OrganizationAndSignificantAccountingPoliciesAccumulatedOtherComprehensiveLossDetails" id="OrganizationAndSignificantAccountingPoliciesAccumulatedOtherComprehensiveLossDetails">
        <!--Parent Role: Organization and Significant Accounting Policies-->
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        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
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      <link:roleType roleURI="http://ionispharma.com/role/OrganizationAndSignificantAccountingPoliciesConvertibleDebtDetails" id="OrganizationAndSignificantAccountingPoliciesConvertibleDebtDetails">
        <!--Parent Role: Organization and Significant Accounting Policies-->
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        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
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      <link:roleType roleURI="http://ionispharma.com/role/OrganizationAndSignificantAccountingPoliciesCallSpreadDetails" id="OrganizationAndSignificantAccountingPoliciesCallSpreadDetails">
        <!--Parent Role: Organization and Significant Accounting Policies-->
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        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
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      <link:roleType roleURI="http://ionispharma.com/role/OrganizationAndSignificantAccountingPoliciesSegmentInformationDetails" id="OrganizationAndSignificantAccountingPoliciesSegmentInformationDetails">
        <!--Parent Role: Organization and Significant Accounting Policies-->
        <link:definition>090136 - Disclosure - Organization and Significant Accounting Policies, Segment Information (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
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      <link:roleType roleURI="http://ionispharma.com/role/OrganizationAndSignificantAccountingPoliciesFairValueMeasurementsDetails" id="OrganizationAndSignificantAccountingPoliciesFairValueMeasurementsDetails">
        <!--Parent Role: Organization and Significant Accounting Policies-->
        <link:definition>090138 - Disclosure - Organization and Significant Accounting Policies, Fair Value Measurements (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
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      <link:roleType roleURI="http://ionispharma.com/role/InvestmentsContractMaturityOfAvailableforsaleSecuritiesDetails" id="InvestmentsContractMaturityOfAvailableforsaleSecuritiesDetails">
        <!--Parent Role: Investments-->
        <link:definition>090200 - Disclosure - Investments, Contract Maturity of Available-for-Sale Securities (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://ionispharma.com/role/InvestmentsSummaryOfInvestmentsDetails" id="InvestmentsSummaryOfInvestmentsDetails">
        <!--Parent Role: Investments-->
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        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://ionispharma.com/role/InvestmentsInvestmentsTemporarilyImpairedDetails" id="InvestmentsInvestmentsTemporarilyImpairedDetails">
        <!--Parent Role: Investments-->
        <link:definition>090204 - Disclosure - Investments, Investments Temporarily Impaired (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
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      <link:roleType roleURI="http://ionispharma.com/role/InvestmentsSummaryOfInvestmentsDetailsCalc2" id="InvestmentsSummaryOfInvestmentsDetailsCalc2">
        <!--Parent Role: Investments, Summary of Investments (Details)-->
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        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
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      <link:roleType roleURI="http://ionispharma.com/role/LongtermObligationsAndCommitmentsLongtermObligationsDetails" id="LongtermObligationsAndCommitmentsLongtermObligationsDetails">
        <!--Parent Role: Long-Term Obligations and Commitments-->
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        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
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      <link:roleType roleURI="http://ionispharma.com/role/LongtermObligationsAndCommitmentsConvertibleNotesDetails" id="LongtermObligationsAndCommitmentsConvertibleNotesDetails">
        <!--Parent Role: Long-Term Obligations and Commitments-->
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        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
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      <link:roleType roleURI="http://ionispharma.com/role/LongtermObligationsAndCommitmentsLineOfCreditArrangementDetails" id="LongtermObligationsAndCommitmentsLineOfCreditArrangementDetails">
        <!--Parent Role: Long-Term Obligations and Commitments-->
        <link:definition>090304 - Disclosure - Long-Term Obligations and Commitments, Line of Credit Arrangement (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
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      <link:roleType roleURI="http://ionispharma.com/role/LongtermObligationsAndCommitmentsResearchAndDevelopmentAndManufacturingFacilitiesDetails" id="LongtermObligationsAndCommitmentsResearchAndDevelopmentAndManufacturingFacilitiesDetails">
        <!--Parent Role: Long-Term Obligations and Commitments-->
        <link:definition>090306 - Disclosure - Long-Term Obligations and Commitments, Research and Development and Manufacturing Facilities (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
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      <link:roleType roleURI="http://ionispharma.com/role/LongtermObligationsAndCommitmentsMaturitySchedulesDetails" id="LongtermObligationsAndCommitmentsMaturitySchedulesDetails">
        <!--Parent Role: Long-Term Obligations and Commitments-->
        <link:definition>090308 - Disclosure - Long-Term Obligations and Commitments, Maturity Schedules (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
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      <link:roleType roleURI="http://ionispharma.com/role/LongtermObligationsAndCommitmentsOperatingLeasesDetails" id="LongtermObligationsAndCommitmentsOperatingLeasesDetails">
        <!--Parent Role: Long-Term Obligations and Commitments-->
        <link:definition>090310 - Disclosure - Long-Term Obligations and Commitments, Operating Leases (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
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      </link:roleType>
      <link:roleType roleURI="http://ionispharma.com/role/OperatingLeasesDetailsCalc01" id="OperatingLeasesDetailsCalc01">
        <!--Parent Role: Long-Term Obligations and Commitments, Operating Leases (Details)-->
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        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
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      <link:roleType roleURI="http://ionispharma.com/role/StockholdersEquityPreferredAndCommonStockDetails" id="StockholdersEquityPreferredAndCommonStockDetails">
        <!--Parent Role: Stockholders' Equity-->
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        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
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      <link:roleType roleURI="http://ionispharma.com/role/StockholdersEquityShareRepurchaseProgramDetails" id="StockholdersEquityShareRepurchaseProgramDetails">
        <!--Parent Role: Stockholders' Equity-->
        <link:definition>090402 - Disclosure - Stockholders' Equity, Share Repurchase Program (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
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      <link:roleType roleURI="http://ionispharma.com/role/StockholdersEquityStockPlansDetails" id="StockholdersEquityStockPlansDetails">
        <!--Parent Role: Stockholders' Equity-->
        <link:definition>090404 - Disclosure - Stockholders' Equity, Stock Plans (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
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      <link:roleType roleURI="http://ionispharma.com/role/StockholdersEquityStockOptionActivityDetails" id="StockholdersEquityStockOptionActivityDetails">
        <!--Parent Role: Stockholders' Equity-->
        <link:definition>090406 - Disclosure - Stockholders' Equity, Stock Option Activity (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
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      <link:roleType roleURI="http://ionispharma.com/role/StockholdersEquityRestrictedStockUnitActivityDetails" id="StockholdersEquityRestrictedStockUnitActivityDetails">
        <!--Parent Role: Stockholders' Equity-->
        <link:definition>090408 - Disclosure - Stockholders' Equity, Restricted Stock Unit Activity (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
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      <link:roleType roleURI="http://ionispharma.com/role/StockholdersEquityStockbasedCompensationExpenseDetails" id="StockholdersEquityStockbasedCompensationExpenseDetails">
        <!--Parent Role: Stockholders' Equity-->
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        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
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      <link:roleType roleURI="http://ionispharma.com/role/StockholdersEquityStockbasedValuationInformationDetails" id="StockholdersEquityStockbasedValuationInformationDetails">
        <!--Parent Role: Stockholders' Equity-->
        <link:definition>090412 - Disclosure - Stockholders' Equity, Stock-based Valuation Information (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
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      <link:roleType roleURI="http://ionispharma.com/role/IncomeTaxesIncomeLossBeforeIncomeTaxesDetails" id="IncomeTaxesIncomeLossBeforeIncomeTaxesDetails">
        <!--Parent Role: Income Taxes-->
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        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
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      <link:roleType roleURI="http://ionispharma.com/role/IncomeTaxesIncomeTaxExpenseBenefitDetails" id="IncomeTaxesIncomeTaxExpenseBenefitDetails">
        <!--Parent Role: Income Taxes-->
        <link:definition>090502 - Disclosure - Income Taxes, Income Tax Expense (Benefit) (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
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      <link:roleType roleURI="http://ionispharma.com/role/IncomeTaxesReconciliationOfStatutoryToEffectiveTaxRateDetails" id="IncomeTaxesReconciliationOfStatutoryToEffectiveTaxRateDetails">
        <!--Parent Role: Income Taxes-->
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        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
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      <link:roleType roleURI="http://ionispharma.com/role/IncomeTaxesDeferredTaxAssetsAndLiabilitiesDetails" id="IncomeTaxesDeferredTaxAssetsAndLiabilitiesDetails">
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        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
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      <link:roleType roleURI="http://ionispharma.com/role/IncomeTaxesTaxCreditCarryforwardsDetails" id="IncomeTaxesTaxCreditCarryforwardsDetails">
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        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
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      <link:roleType roleURI="http://ionispharma.com/role/IncomeTaxesGrossUnrecognizedTaxBenefitsDetails" id="IncomeTaxesGrossUnrecognizedTaxBenefitsDetails">
        <!--Parent Role: Income Taxes-->
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        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
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        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
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      <link:roleType roleURI="http://ionispharma.com/role/CollaborativeArrangementsAndLicensingAgreementsAstrazenecaDetails" id="CollaborativeArrangementsAndLicensingAgreementsAstrazenecaDetails">
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        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
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      <link:roleType roleURI="http://ionispharma.com/role/CollaborativeArrangementsAndLicensingAgreementsBayerDetails" id="CollaborativeArrangementsAndLicensingAgreementsBayerDetails">
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        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
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      <link:roleType roleURI="http://ionispharma.com/role/CollaborativeArrangementsAndLicensingAgreementsGskDetails" id="CollaborativeArrangementsAndLicensingAgreementsGskDetails">
        <!--Parent Role: Collaborative Arrangements and Licensing Agreements-->
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        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
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      <link:roleType roleURI="http://ionispharma.com/role/CollaborativeArrangementsAndLicensingAgreementsJanssenBiotechIncDetails" id="CollaborativeArrangementsAndLicensingAgreementsJanssenBiotechIncDetails">
        <!--Parent Role: Collaborative Arrangements and Licensing Agreements-->
        <link:definition>090608 - Disclosure - Collaborative Arrangements and Licensing Agreements, Janssen Biotech, Inc. (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
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      <link:roleType roleURI="http://ionispharma.com/role/CollaborativeArrangementsAndLicensingAgreementsNovartisDetails" id="CollaborativeArrangementsAndLicensingAgreementsNovartisDetails">
        <!--Parent Role: Collaborative Arrangements and Licensing Agreements-->
        <link:definition>090610 - Disclosure - Collaborative Arrangements and Licensing Agreements, Novartis (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
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      <link:roleType roleURI="http://ionispharma.com/role/CollaborativeArrangementsAndLicensingAgreementsPfizerDetails" id="CollaborativeArrangementsAndLicensingAgreementsPfizerDetails">
        <!--Parent Role: Collaborative Arrangements and Licensing Agreements-->
        <link:definition>090612 - Disclosure - Collaborative Arrangements and Licensing Agreements, Pfizer (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
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      <link:roleType roleURI="http://ionispharma.com/role/CollaborativeArrangementsAndLicensingAgreementsPtcTherapeuticsDetails" id="CollaborativeArrangementsAndLicensingAgreementsPtcTherapeuticsDetails">
        <!--Parent Role: Collaborative Arrangements and Licensing Agreements-->
        <link:definition>090614 - Disclosure - Collaborative Arrangements and Licensing Agreements, PTC Therapeutics (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
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<DOCUMENT>
<TYPE>EX-101.LAB
<SEQUENCE>17
<FILENAME>ions-20201231_lab.xml
<DESCRIPTION>XBRL TAXONOMY EXTENSION LABEL LINKBASE
<TEXT>
<XBRL>
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    <link:label xlink:type="resource" xlink:label="us-gaap_AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation_lbl1" xml:lang="en-US" id="us-gaap_AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation_lbl1">Share-based Payment Arrangement, Decrease for Tax Withholding Obligation</link:label>
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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>
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AmortizationOfFinancingCosts" xlink:to="us-gaap_AmortizationOfFinancingCosts_lbl" xlink:title="label: AmortizationOfFinancingCosts to us-gaap_AmortizationOfFinancingCosts_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_AmortizationOfFinancingCosts_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_AmortizationOfFinancingCosts_lbl1" xml:lang="en-US" id="us-gaap_AmortizationOfFinancingCosts_lbl1">Amortization of Debt Issuance Costs</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AmortizationOfFinancingCosts" xlink:to="us-gaap_AmortizationOfFinancingCosts_lbl1" xlink:title="label: AmortizationOfFinancingCosts to us-gaap_AmortizationOfFinancingCosts_lbl1" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_AmortizationOfIntangibleAssets_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_AmortizationOfIntangibleAssets_lbl" xml:lang="en-US" id="us-gaap_AmortizationOfIntangibleAssets_lbl">Amortization of patents</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AmortizationOfIntangibleAssets" xlink:to="us-gaap_AmortizationOfIntangibleAssets_lbl" xlink:title="label: AmortizationOfIntangibleAssets to us-gaap_AmortizationOfIntangibleAssets_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_AmortizationOfIntangibleAssets_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_AmortizationOfIntangibleAssets_lbl1" xml:lang="en-US" id="us-gaap_AmortizationOfIntangibleAssets_lbl1">Amortization of Intangible Assets</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_AmortizationOfDebtDiscountPremium_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_AmortizationOfDebtDiscountPremium_lbl" xml:lang="en-US" id="us-gaap_AmortizationOfDebtDiscountPremium_lbl">Amortization of convertible senior notes discount</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_AmortizationOfDebtDiscountPremium_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_AmortizationOfDebtDiscountPremium_lbl1" xml:lang="en-US" id="us-gaap_AmortizationOfDebtDiscountPremium_lbl1">Amortization of Debt Discount (Premium)</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_AmortizationOfFinancingCostsAndDiscounts_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_AmortizationOfFinancingCostsAndDiscounts_lbl1" xml:lang="en-US" id="us-gaap_AmortizationOfFinancingCostsAndDiscounts_lbl1">Amortization of Debt Issuance Costs and Discounts</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AmortizationOfFinancingCostsAndDiscounts" xlink:to="us-gaap_AmortizationOfFinancingCostsAndDiscounts_lbl1" xlink:title="label: AmortizationOfFinancingCostsAndDiscounts to us-gaap_AmortizationOfFinancingCostsAndDiscounts_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_AssetImpairmentChargesAbstract" xlink:label="AssetImpairmentChargesAbstract" xlink:title="AssetImpairmentChargesAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_AssetImpairmentChargesAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_AssetImpairmentChargesAbstract_lbl" xml:lang="en-US" id="us-gaap_AssetImpairmentChargesAbstract_lbl">Long-Lived Assets [Abstract]</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_AssetImpairmentChargesAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_AssetImpairmentChargesAbstract_lbl1" xml:lang="en-US" id="us-gaap_AssetImpairmentChargesAbstract_lbl1">Asset Impairment Charges [Abstract]</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_AssetsFairValueDisclosure_lbl" xlink:role="http://www.xbrl.org/2003/role/totalLabel" xlink:title="us-gaap_AssetsFairValueDisclosure_lbl" xml:lang="en-US" id="us-gaap_AssetsFairValueDisclosure_lbl">Total</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_AssetsFairValueDisclosure_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_AssetsFairValueDisclosure_lbl1" xml:lang="en-US" id="us-gaap_AssetsFairValueDisclosure_lbl1">Assets, Fair Value Disclosure</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_AssetsAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_AssetsAbstract_lbl1" xml:lang="en-US" id="us-gaap_AssetsAbstract_lbl1">Assets [Abstract]</link:label>
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="Assets" xlink:to="us-gaap_Assets_lbl" xlink:title="label: Assets to us-gaap_Assets_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_Assets_lbl1" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_Assets_lbl1" xml:lang="en-US" id="us-gaap_Assets_lbl1">Total assets</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="Assets" xlink:to="us-gaap_Assets_lbl1" xlink:title="label: Assets to us-gaap_Assets_lbl1" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_AssetsCurrent_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_AssetsCurrent_lbl1" xml:lang="en-US" id="us-gaap_AssetsCurrent_lbl1">Assets, Current</link:label>
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CaliforniaFranchiseTaxBoardMember" xlink:to="us-gaap_CaliforniaFranchiseTaxBoardMember_lbl1" xlink:title="label: CaliforniaFranchiseTaxBoardMember to us-gaap_CaliforniaFranchiseTaxBoardMember_lbl1" />
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CashAndCashEquivalentsAtCarryingValue" xlink:to="us-gaap_CashAndCashEquivalentsAtCarryingValue_lbl1" xlink:title="label: CashAndCashEquivalentsAtCarryingValue to us-gaap_CashAndCashEquivalentsAtCarryingValue_lbl1" />
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect" xlink:to="us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect_lbl" xlink:title="label: CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect to us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect_lbl" />
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    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_CashAndCashEquivalentsMember" xlink:label="CashAndCashEquivalentsMember" xlink:title="CashAndCashEquivalentsMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CashAndCashEquivalentsMember_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_CashAndCashEquivalentsMember_lbl" xml:lang="en-US" id="us-gaap_CashAndCashEquivalentsMember_lbl">Cash and Cash Equivalents [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CashAndCashEquivalentsMember" xlink:to="us-gaap_CashAndCashEquivalentsMember_lbl" xlink:title="label: CashAndCashEquivalentsMember to us-gaap_CashAndCashEquivalentsMember_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_CashAndCashEquivalentsFairValueDisclosure" xlink:label="CashAndCashEquivalentsFairValueDisclosure" xlink:title="CashAndCashEquivalentsFairValueDisclosure" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_CashAndCashEquivalentsFairValueDisclosure_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_CashAndCashEquivalentsFairValueDisclosure_lbl1" xml:lang="en-US" id="us-gaap_CashAndCashEquivalentsFairValueDisclosure_lbl1">Cash and Cash Equivalents, Fair Value Disclosure</link:label>
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    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ContractWithCustomerLiability" xlink:label="ContractWithCustomerLiability" xlink:title="ContractWithCustomerLiability" />
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    <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="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.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>
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    <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="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.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="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ContractWithCustomerLiabilityRevenueRecognized" xlink:label="ContractWithCustomerLiabilityRevenueRecognized" xlink:title="ContractWithCustomerLiabilityRevenueRecognized" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ContractWithCustomerLiabilityRevenueRecognized_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_ContractWithCustomerLiabilityRevenueRecognized_lbl" xml:lang="en-US" id="us-gaap_ContractWithCustomerLiabilityRevenueRecognized_lbl">Revenue recognized from amounts in beginning deferred revenue balance</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ContractWithCustomerLiabilityRevenueRecognized" xlink:to="us-gaap_ContractWithCustomerLiabilityRevenueRecognized_lbl" xlink:title="label: ContractWithCustomerLiabilityRevenueRecognized to us-gaap_ContractWithCustomerLiabilityRevenueRecognized_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ContractWithCustomerLiabilityRevenueRecognized_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ContractWithCustomerLiabilityRevenueRecognized_lbl1" xml:lang="en-US" id="us-gaap_ContractWithCustomerLiabilityRevenueRecognized_lbl1">Contract with Customer, Liability, Revenue Recognized</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ContractWithCustomerLiabilityRevenueRecognized" xlink:to="us-gaap_ContractWithCustomerLiabilityRevenueRecognized_lbl1" xlink:title="label: ContractWithCustomerLiabilityRevenueRecognized to us-gaap_ContractWithCustomerLiabilityRevenueRecognized_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.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="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.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="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ContractReceivablesAbstract" xlink:label="ContractReceivablesAbstract" xlink:title="ContractReceivablesAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ContractReceivablesAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_ContractReceivablesAbstract_lbl" xml:lang="en-US" id="us-gaap_ContractReceivablesAbstract_lbl">Contracts Receivable [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ContractReceivablesAbstract" xlink:to="us-gaap_ContractReceivablesAbstract_lbl" xlink:title="label: ContractReceivablesAbstract to us-gaap_ContractReceivablesAbstract_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ContractReceivablesAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ContractReceivablesAbstract_lbl1" xml:lang="en-US" id="us-gaap_ContractReceivablesAbstract_lbl1">Contracts Receivable [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ContractReceivablesAbstract" xlink:to="us-gaap_ContractReceivablesAbstract_lbl1" xlink:title="label: ContractReceivablesAbstract to us-gaap_ContractReceivablesAbstract_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ContractualObligationDueInNextTwelveMonths" xlink:label="ContractualObligationDueInNextTwelveMonths" xlink:title="ContractualObligationDueInNextTwelveMonths" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ContractualObligationDueInNextTwelveMonths_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_ContractualObligationDueInNextTwelveMonths_lbl" xml:lang="en-US" id="us-gaap_ContractualObligationDueInNextTwelveMonths_lbl">2021</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ContractualObligationDueInNextTwelveMonths" xlink:to="us-gaap_ContractualObligationDueInNextTwelveMonths_lbl" xlink:title="label: ContractualObligationDueInNextTwelveMonths to us-gaap_ContractualObligationDueInNextTwelveMonths_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ContractualObligationDueInNextTwelveMonths_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ContractualObligationDueInNextTwelveMonths_lbl1" xml:lang="en-US" id="us-gaap_ContractualObligationDueInNextTwelveMonths_lbl1">Contractual Obligation, to be Paid, Year One</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ContractualObligationDueInNextTwelveMonths" xlink:to="us-gaap_ContractualObligationDueInNextTwelveMonths_lbl1" xlink:title="label: ContractualObligationDueInNextTwelveMonths to us-gaap_ContractualObligationDueInNextTwelveMonths_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ContractualObligationDueInFifthYear" xlink:label="ContractualObligationDueInFifthYear" xlink:title="ContractualObligationDueInFifthYear" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ContractualObligationDueInFifthYear_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_ContractualObligationDueInFifthYear_lbl" xml:lang="en-US" id="us-gaap_ContractualObligationDueInFifthYear_lbl">2025</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_ContractualObligationDueInFifthYear_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ContractualObligationDueInFifthYear_lbl1" xml:lang="en-US" id="us-gaap_ContractualObligationDueInFifthYear_lbl1">Contractual Obligation, to be Paid, Year Five</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ContractualObligationDueInFifthYear" xlink:to="us-gaap_ContractualObligationDueInFifthYear_lbl1" xlink:title="label: ContractualObligationDueInFifthYear to us-gaap_ContractualObligationDueInFifthYear_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ContractualObligationDueInFourthYear" xlink:label="ContractualObligationDueInFourthYear" xlink:title="ContractualObligationDueInFourthYear" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ContractualObligationDueInFourthYear_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_ContractualObligationDueInFourthYear_lbl" xml:lang="en-US" id="us-gaap_ContractualObligationDueInFourthYear_lbl">2024</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_ContractualObligationDueInFourthYear_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ContractualObligationDueInFourthYear_lbl1" xml:lang="en-US" id="us-gaap_ContractualObligationDueInFourthYear_lbl1">Contractual Obligation, to be Paid, Year Four</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ContractualObligationDueInFourthYear" xlink:to="us-gaap_ContractualObligationDueInFourthYear_lbl1" xlink:title="label: ContractualObligationDueInFourthYear to us-gaap_ContractualObligationDueInFourthYear_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ContractualObligation" xlink:label="ContractualObligation" xlink:title="ContractualObligation" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ContractualObligation_lbl" xlink:role="http://www.xbrl.org/2003/role/totalLabel" xlink:title="us-gaap_ContractualObligation_lbl" xml:lang="en-US" id="us-gaap_ContractualObligation_lbl">Subtotal</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ContractualObligation" xlink:to="us-gaap_ContractualObligation_lbl" xlink:title="label: ContractualObligation to us-gaap_ContractualObligation_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ContractualObligation_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ContractualObligation_lbl1" xml:lang="en-US" id="us-gaap_ContractualObligation_lbl1">Contractual Obligation</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ContractualObligation" xlink:to="us-gaap_ContractualObligation_lbl1" xlink:title="label: ContractualObligation to us-gaap_ContractualObligation_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ContractualObligationDueInSecondYear" xlink:label="ContractualObligationDueInSecondYear" xlink:title="ContractualObligationDueInSecondYear" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ContractualObligationDueInSecondYear_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_ContractualObligationDueInSecondYear_lbl" xml:lang="en-US" id="us-gaap_ContractualObligationDueInSecondYear_lbl">2022</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_ContractualObligationDueInSecondYear_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ContractualObligationDueInSecondYear_lbl1" xml:lang="en-US" id="us-gaap_ContractualObligationDueInSecondYear_lbl1">Contractual Obligation, to be Paid, Year Two</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ContractualObligationDueInSecondYear" xlink:to="us-gaap_ContractualObligationDueInSecondYear_lbl1" xlink:title="label: ContractualObligationDueInSecondYear to us-gaap_ContractualObligationDueInSecondYear_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ContractualObligationDueAfterFifthYear" xlink:label="ContractualObligationDueAfterFifthYear" xlink:title="ContractualObligationDueAfterFifthYear" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ContractualObligationDueAfterFifthYear_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_ContractualObligationDueAfterFifthYear_lbl" xml:lang="en-US" id="us-gaap_ContractualObligationDueAfterFifthYear_lbl">Thereafter</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_ContractualObligationDueAfterFifthYear_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ContractualObligationDueAfterFifthYear_lbl1" xml:lang="en-US" id="us-gaap_ContractualObligationDueAfterFifthYear_lbl1">Contractual Obligation, 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="ContractualObligationDueAfterFifthYear" xlink:to="us-gaap_ContractualObligationDueAfterFifthYear_lbl1" xlink:title="label: ContractualObligationDueAfterFifthYear to us-gaap_ContractualObligationDueAfterFifthYear_lbl1" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_ContractualObligationDueInThirdYear_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_ContractualObligationDueInThirdYear_lbl" xml:lang="en-US" id="us-gaap_ContractualObligationDueInThirdYear_lbl">2023</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ContractualObligationDueInThirdYear" xlink:to="us-gaap_ContractualObligationDueInThirdYear_lbl" xlink:title="label: ContractualObligationDueInThirdYear to us-gaap_ContractualObligationDueInThirdYear_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ContractualObligationDueInThirdYear_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ContractualObligationDueInThirdYear_lbl1" xml:lang="en-US" id="us-gaap_ContractualObligationDueInThirdYear_lbl1">Contractual Obligation, to be Paid, Year Three</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ContractualObligationDueInThirdYear" xlink:to="us-gaap_ContractualObligationDueInThirdYear_lbl1" xlink:title="label: ContractualObligationDueInThirdYear to us-gaap_ContractualObligationDueInThirdYear_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ConvertibleDebtCurrent" xlink:label="ConvertibleDebtCurrent" xlink:title="ConvertibleDebtCurrent" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ConvertibleDebtCurrent_lbl" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="us-gaap_ConvertibleDebtCurrent_lbl" xml:lang="en-US" id="us-gaap_ConvertibleDebtCurrent_lbl">Current debt</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleDebtCurrent" xlink:to="us-gaap_ConvertibleDebtCurrent_lbl" xlink:title="label: ConvertibleDebtCurrent to us-gaap_ConvertibleDebtCurrent_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ConvertibleDebtCurrent_lbl1" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_ConvertibleDebtCurrent_lbl1" xml:lang="en-US" id="us-gaap_ConvertibleDebtCurrent_lbl1">1 percent convertible senior notes</link:label>
    <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:label xlink:type="resource" xlink:label="us-gaap_ConvertibleDebtCurrent_lbl2" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ConvertibleDebtCurrent_lbl2" xml:lang="en-US" id="us-gaap_ConvertibleDebtCurrent_lbl2">Convertible Debt, Current</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleDebtCurrent" xlink:to="us-gaap_ConvertibleDebtCurrent_lbl2" xlink:title="label: ConvertibleDebtCurrent to us-gaap_ConvertibleDebtCurrent_lbl2" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ConvertibleDebt" xlink:label="ConvertibleDebt" xlink:title="ConvertibleDebt" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ConvertibleDebt_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_ConvertibleDebt_lbl" xml:lang="en-US" id="us-gaap_ConvertibleDebt_lbl">Convertible senior notes</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleDebt" xlink:to="us-gaap_ConvertibleDebt_lbl" xlink:title="label: ConvertibleDebt to us-gaap_ConvertibleDebt_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ConvertibleDebt_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ConvertibleDebt_lbl1" xml:lang="en-US" id="us-gaap_ConvertibleDebt_lbl1">Convertible Debt</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleDebt" xlink:to="us-gaap_ConvertibleDebt_lbl1" xlink:title="label: ConvertibleDebt to us-gaap_ConvertibleDebt_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ConvertibleDebtNoncurrent" xlink:label="ConvertibleDebtNoncurrent" xlink:title="ConvertibleDebtNoncurrent" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ConvertibleDebtNoncurrent_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_ConvertibleDebtNoncurrent_lbl" xml:lang="en-US" id="us-gaap_ConvertibleDebtNoncurrent_lbl">Convertible senior notes</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleDebtNoncurrent" xlink:to="us-gaap_ConvertibleDebtNoncurrent_lbl" xlink:title="label: ConvertibleDebtNoncurrent to us-gaap_ConvertibleDebtNoncurrent_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ConvertibleDebtNoncurrent_lbl1" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="us-gaap_ConvertibleDebtNoncurrent_lbl1" xml:lang="en-US" id="us-gaap_ConvertibleDebtNoncurrent_lbl1">Long-term debt</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleDebtNoncurrent" xlink:to="us-gaap_ConvertibleDebtNoncurrent_lbl1" xlink:title="label: ConvertibleDebtNoncurrent to us-gaap_ConvertibleDebtNoncurrent_lbl1" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ConvertibleDebtNoncurrent_lbl2" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ConvertibleDebtNoncurrent_lbl2" xml:lang="en-US" id="us-gaap_ConvertibleDebtNoncurrent_lbl2">Convertible Debt, Noncurrent</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleDebtNoncurrent" xlink:to="us-gaap_ConvertibleDebtNoncurrent_lbl2" xlink:title="label: ConvertibleDebtNoncurrent to us-gaap_ConvertibleDebtNoncurrent_lbl2" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract" xlink:label="ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract" xlink:title="ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract_lbl" xml:lang="en-US" id="us-gaap_ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract_lbl">Convertible Notes [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract" xlink:to="us-gaap_ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract_lbl" xlink:title="label: ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract to us-gaap_ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ConvertibleDebtTableTextBlock" xlink:label="ConvertibleDebtTableTextBlock" xlink:title="ConvertibleDebtTableTextBlock" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ConvertibleDebtTableTextBlock_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ConvertibleDebtTableTextBlock_lbl" xml:lang="en-US" id="us-gaap_ConvertibleDebtTableTextBlock_lbl">Convertible Notes</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleDebtTableTextBlock" xlink:to="us-gaap_ConvertibleDebtTableTextBlock_lbl" xlink:title="label: ConvertibleDebtTableTextBlock to us-gaap_ConvertibleDebtTableTextBlock_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.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="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.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 products 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_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="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.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 Products Sold</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="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.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 Products Sold [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="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_CostsAndExpensesAbstract" xlink:label="CostsAndExpensesAbstract" xlink:title="CostsAndExpensesAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CostsAndExpensesAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_CostsAndExpensesAbstract_lbl" xml:lang="en-US" id="us-gaap_CostsAndExpensesAbstract_lbl">Expenses:</link:label>
    <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" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CostsAndExpensesAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_CostsAndExpensesAbstract_lbl1" xml:lang="en-US" id="us-gaap_CostsAndExpensesAbstract_lbl1">Costs and Expenses [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CostsAndExpensesAbstract" xlink:to="us-gaap_CostsAndExpensesAbstract_lbl1" xlink:title="label: CostsAndExpensesAbstract to us-gaap_CostsAndExpensesAbstract_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_CostsAndExpenses" xlink:label="CostsAndExpenses" xlink:title="CostsAndExpenses" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CostsAndExpenses_lbl" xlink:role="http://www.xbrl.org/2003/role/totalLabel" xlink:title="us-gaap_CostsAndExpenses_lbl" xml:lang="en-US" id="us-gaap_CostsAndExpenses_lbl">Total operating expenses</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CostsAndExpenses" xlink:to="us-gaap_CostsAndExpenses_lbl" xlink:title="label: CostsAndExpenses to us-gaap_CostsAndExpenses_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CostsAndExpenses_lbl1" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="us-gaap_CostsAndExpenses_lbl1" xml:lang="en-US" id="us-gaap_CostsAndExpenses_lbl1">Total operating expenses</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CostsAndExpenses" xlink:to="us-gaap_CostsAndExpenses_lbl1" xlink:title="label: CostsAndExpenses to us-gaap_CostsAndExpenses_lbl1" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CostsAndExpenses_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_CostsAndExpenses_lbl2" xml:lang="en-US" id="us-gaap_CostsAndExpenses_lbl2">Operating expenses</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CostsAndExpenses" xlink:to="us-gaap_CostsAndExpenses_lbl2" xlink:title="label: CostsAndExpenses to us-gaap_CostsAndExpenses_lbl2" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CostsAndExpenses_lbl3" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_CostsAndExpenses_lbl3" xml:lang="en-US" id="us-gaap_CostsAndExpenses_lbl3">Costs and Expenses</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CostsAndExpenses" xlink:to="us-gaap_CostsAndExpenses_lbl3" xlink:title="label: CostsAndExpenses to us-gaap_CostsAndExpenses_lbl3" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_CreditFacilityDomain_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_CreditFacilityDomain_lbl" xml:lang="en-US" id="us-gaap_CreditFacilityDomain_lbl">Credit Facility [Domain]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CreditFacilityDomain" xlink:to="us-gaap_CreditFacilityDomain_lbl" xlink:title="label: CreditFacilityDomain to us-gaap_CreditFacilityDomain_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_CreditFacilityAxis" xlink:label="CreditFacilityAxis" xlink:title="CreditFacilityAxis" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CreditFacilityAxis_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_CreditFacilityAxis_lbl" xml:lang="en-US" id="us-gaap_CreditFacilityAxis_lbl">Credit Facility [Axis]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CreditFacilityAxis" xlink:to="us-gaap_CreditFacilityAxis_lbl" xlink:title="label: CreditFacilityAxis to us-gaap_CreditFacilityAxis_lbl" />
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    <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>
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    <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>
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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: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" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_DeferredFinanceCostsNet_lbl" xlink:role="http://www.xbrl.org/2009/role/negatedLabel" xlink:title="us-gaap_DeferredFinanceCostsNet_lbl" xml:lang="en-US" id="us-gaap_DeferredFinanceCostsNet_lbl">Less: debt issuance costs</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_DeferredRentCredit_lbl" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="us-gaap_DeferredRentCredit_lbl" xml:lang="en-US" id="us-gaap_DeferredRentCredit_lbl">Plus: lease liabilities</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_DeferredRentCredit_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_DeferredRentCredit_lbl1" xml:lang="en-US" id="us-gaap_DeferredRentCredit_lbl1">Deferred Rent Credit</link:label>
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DeferredTaxAssetsGross" xlink:to="us-gaap_DeferredTaxAssetsGross_lbl1" xlink:title="label: DeferredTaxAssetsGross to us-gaap_DeferredTaxAssetsGross_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_DeferredStateAndLocalIncomeTaxExpenseBenefit" xlink:label="DeferredStateAndLocalIncomeTaxExpenseBenefit" xlink:title="DeferredStateAndLocalIncomeTaxExpenseBenefit" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_EquitySecuritiesFvNiCost_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_EquitySecuritiesFvNiCost_lbl1" xml:lang="en-US" id="us-gaap_EquitySecuritiesFvNiCost_lbl1">Equity Securities, FV-NI, Cost</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_EquitySecuritiesFvNiUnrealizedLoss_lbl" xlink:role="http://www.xbrl.org/2009/role/negatedLabel" xlink:title="us-gaap_EquitySecuritiesFvNiUnrealizedLoss_lbl" xml:lang="en-US" id="us-gaap_EquitySecuritiesFvNiUnrealizedLoss_lbl">Gross unrealized losses</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_EquitySecuritiesFvNiUnrealizedLoss_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_EquitySecuritiesFvNiUnrealizedLoss_lbl1" xml:lang="en-US" id="us-gaap_EquitySecuritiesFvNiUnrealizedLoss_lbl1">Equity Securities, FV-NI, Unrealized Loss</link:label>
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    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_EquityComponentDomain" xlink:label="EquityComponentDomain" xlink:title="EquityComponentDomain" />
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    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_EquitySecuritiesFvNiUnrealizedGain" xlink:label="EquitySecuritiesFvNiUnrealizedGain" xlink:title="EquitySecuritiesFvNiUnrealizedGain" />
    <link:label xlink:type="resource" xlink:label="us-gaap_EquitySecuritiesFvNiUnrealizedGain_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_EquitySecuritiesFvNiUnrealizedGain_lbl" xml:lang="en-US" id="us-gaap_EquitySecuritiesFvNiUnrealizedGain_lbl">Gross unrealized gains</link:label>
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EquitySecuritiesFvNiUnrealizedGain" xlink:to="us-gaap_EquitySecuritiesFvNiUnrealizedGain_lbl1" xlink:title="label: EquitySecuritiesFvNiUnrealizedGain to us-gaap_EquitySecuritiesFvNiUnrealizedGain_lbl1" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_EquitySecuritiesFvNi_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_EquitySecuritiesFvNi_lbl" xml:lang="en-US" id="us-gaap_EquitySecuritiesFvNi_lbl">Investment in ProQR NV</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_EquitySecuritiesFvNi_lbl1" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="us-gaap_EquitySecuritiesFvNi_lbl1" xml:lang="en-US" id="us-gaap_EquitySecuritiesFvNi_lbl1">Estimated fair value</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_EquitySecuritiesFvNi_lbl2" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_EquitySecuritiesFvNi_lbl2" xml:lang="en-US" id="us-gaap_EquitySecuritiesFvNi_lbl2">Equity Securities, FV-NI</link:label>
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    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.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="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_FairValueNetAssetLiabilityAbstract" xlink:label="FairValueNetAssetLiabilityAbstract" xlink:title="FairValueNetAssetLiabilityAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_FairValueNetAssetLiabilityAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_FairValueNetAssetLiabilityAbstract_lbl" xml:lang="en-US" id="us-gaap_FairValueNetAssetLiabilityAbstract_lbl">Fair Value Measurements [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="FairValueNetAssetLiabilityAbstract" xlink:to="us-gaap_FairValueNetAssetLiabilityAbstract_lbl" xlink:title="label: FairValueNetAssetLiabilityAbstract to us-gaap_FairValueNetAssetLiabilityAbstract_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_FairValueNetAssetLiabilityAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_FairValueNetAssetLiabilityAbstract_lbl1" xml:lang="en-US" id="us-gaap_FairValueNetAssetLiabilityAbstract_lbl1">Fair Value, Net Asset (Liability) [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="FairValueNetAssetLiabilityAbstract" xlink:to="us-gaap_FairValueNetAssetLiabilityAbstract_lbl1" xlink:title="label: FairValueNetAssetLiabilityAbstract to us-gaap_FairValueNetAssetLiabilityAbstract_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_FairValueMeasurementPolicyPolicyTextBlock" xlink:label="FairValueMeasurementPolicyPolicyTextBlock" xlink:title="FairValueMeasurementPolicyPolicyTextBlock" />
    <link:label xlink:type="resource" xlink:label="us-gaap_FairValueMeasurementPolicyPolicyTextBlock_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_FairValueMeasurementPolicyPolicyTextBlock_lbl" xml:lang="en-US" id="us-gaap_FairValueMeasurementPolicyPolicyTextBlock_lbl">Fair Value Measurements</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="FairValueMeasurementPolicyPolicyTextBlock" xlink:to="us-gaap_FairValueMeasurementPolicyPolicyTextBlock_lbl" xlink:title="label: FairValueMeasurementPolicyPolicyTextBlock to us-gaap_FairValueMeasurementPolicyPolicyTextBlock_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_FairValueMeasurementPolicyPolicyTextBlock_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_FairValueMeasurementPolicyPolicyTextBlock_lbl1" xml:lang="en-US" id="us-gaap_FairValueMeasurementPolicyPolicyTextBlock_lbl1">Fair Value Measurement, Policy [Policy Text Block]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="FairValueMeasurementPolicyPolicyTextBlock" xlink:to="us-gaap_FairValueMeasurementPolicyPolicyTextBlock_lbl1" xlink:title="label: FairValueMeasurementPolicyPolicyTextBlock to us-gaap_FairValueMeasurementPolicyPolicyTextBlock_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems" xlink:label="FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems" xlink:title="FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems" />
    <link:label xlink:type="resource" xlink:label="us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems_lbl" xml:lang="en-US" id="us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems_lbl">Fair Value, Assets and Liabilities Measured on Recurring and Nonrecurring Basis [Line Items]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems" xlink:to="us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems_lbl" xlink:title="label: FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems to us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_FairValueByFairValueHierarchyLevelAxis" xlink:label="FairValueByFairValueHierarchyLevelAxis" xlink:title="FairValueByFairValueHierarchyLevelAxis" />
    <link:label xlink:type="resource" xlink:label="us-gaap_FairValueByFairValueHierarchyLevelAxis_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_FairValueByFairValueHierarchyLevelAxis_lbl" xml:lang="en-US" id="us-gaap_FairValueByFairValueHierarchyLevelAxis_lbl">Fair Value, Hierarchy [Axis]</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_FairValueMeasurementsFairValueHierarchyDomain_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_FairValueMeasurementsFairValueHierarchyDomain_lbl" xml:lang="en-US" id="us-gaap_FairValueMeasurementsFairValueHierarchyDomain_lbl">Fair Value Hierarchy [Domain]</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_FairValueMeasurementsRecurringMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_FairValueMeasurementsRecurringMember_lbl1" xml:lang="en-US" id="us-gaap_FairValueMeasurementsRecurringMember_lbl1">Fair Value, Recurring [Member]</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_FairValueMeasurementFrequencyDomain_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_FairValueMeasurementFrequencyDomain_lbl" xml:lang="en-US" id="us-gaap_FairValueMeasurementFrequencyDomain_lbl">Fair Value, Measurement Frequency [Domain]</link:label>
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    <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>
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    <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="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_InterestPaidNet" xlink:label="InterestPaidNet" xlink:title="InterestPaidNet" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InterestPaidNet_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_InterestPaidNet_lbl" xml:lang="en-US" id="us-gaap_InterestPaidNet_lbl">Interest paid</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InterestPaidNet" xlink:to="us-gaap_InterestPaidNet_lbl" xlink:title="label: InterestPaidNet to us-gaap_InterestPaidNet_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InterestPaidNet_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_InterestPaidNet_lbl1" xml:lang="en-US" id="us-gaap_InterestPaidNet_lbl1">Interest Paid, Excluding Capitalized Interest, Operating Activities</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InterestPaidNet" xlink:to="us-gaap_InterestPaidNet_lbl1" xlink:title="label: InterestPaidNet to us-gaap_InterestPaidNet_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_InternalRevenueServiceIRSMember" xlink:label="InternalRevenueServiceIRSMember" xlink:title="InternalRevenueServiceIRSMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InternalRevenueServiceIRSMember_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_InternalRevenueServiceIRSMember_lbl" xml:lang="en-US" id="us-gaap_InternalRevenueServiceIRSMember_lbl">Federal [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InternalRevenueServiceIRSMember" xlink:to="us-gaap_InternalRevenueServiceIRSMember_lbl" xlink:title="label: InternalRevenueServiceIRSMember to us-gaap_InternalRevenueServiceIRSMember_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.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="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_InventoryWriteDown" xlink:label="InventoryWriteDown" xlink:title="InventoryWriteDown" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InventoryWriteDown_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_InventoryWriteDown_lbl" xml:lang="en-US" id="us-gaap_InventoryWriteDown_lbl">Inventory write-off</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InventoryWriteDown" xlink:to="us-gaap_InventoryWriteDown_lbl" xlink:title="label: InventoryWriteDown to us-gaap_InventoryWriteDown_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InventoryWriteDown_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_InventoryWriteDown_lbl1" xml:lang="en-US" id="us-gaap_InventoryWriteDown_lbl1">Inventory Write-down</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InventoryWriteDown" xlink:to="us-gaap_InventoryWriteDown_lbl1" xlink:title="label: InventoryWriteDown to us-gaap_InventoryWriteDown_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_InventoryLineItems" xlink:label="InventoryLineItems" xlink:title="InventoryLineItems" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InventoryLineItems_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_InventoryLineItems_lbl" xml:lang="en-US" id="us-gaap_InventoryLineItems_lbl">Inventory [Line Items]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InventoryLineItems" xlink:to="us-gaap_InventoryLineItems_lbl" xlink:title="label: InventoryLineItems to us-gaap_InventoryLineItems_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_InventoryCurrentTable" xlink:label="InventoryCurrentTable" xlink:title="InventoryCurrentTable" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InventoryCurrentTable_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_InventoryCurrentTable_lbl" xml:lang="en-US" id="us-gaap_InventoryCurrentTable_lbl">Inventory, Current [Table]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InventoryCurrentTable" xlink:to="us-gaap_InventoryCurrentTable_lbl" xlink:title="label: InventoryCurrentTable to us-gaap_InventoryCurrentTable_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.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="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.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="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_InventoryWorkInProcess" xlink:label="InventoryWorkInProcess" xlink:title="InventoryWorkInProcess" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InventoryWorkInProcess_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_InventoryWorkInProcess_lbl" xml:lang="en-US" id="us-gaap_InventoryWorkInProcess_lbl">Work in process</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InventoryWorkInProcess" xlink:to="us-gaap_InventoryWorkInProcess_lbl" xlink:title="label: InventoryWorkInProcess to us-gaap_InventoryWorkInProcess_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InventoryWorkInProcess_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_InventoryWorkInProcess_lbl1" xml:lang="en-US" id="us-gaap_InventoryWorkInProcess_lbl1">Inventory, Work in Process, Gross</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InventoryWorkInProcess" xlink:to="us-gaap_InventoryWorkInProcess_lbl1" xlink:title="label: InventoryWorkInProcess to us-gaap_InventoryWorkInProcess_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.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 Valuation [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InventoryNetAbstract" xlink:to="us-gaap_InventoryNetAbstract_lbl" xlink:title="label: InventoryNetAbstract to us-gaap_InventoryNetAbstract_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InventoryNetAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_InventoryNetAbstract_lbl1" xml:lang="en-US" id="us-gaap_InventoryNetAbstract_lbl1">Inventory, Net [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InventoryNetAbstract" xlink:to="us-gaap_InventoryNetAbstract_lbl1" xlink:title="label: InventoryNetAbstract to us-gaap_InventoryNetAbstract_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.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">Inventory Valuation</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InventoryPolicyTextBlock" xlink:to="us-gaap_InventoryPolicyTextBlock_lbl" xlink:title="label: InventoryPolicyTextBlock to us-gaap_InventoryPolicyTextBlock_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InventoryPolicyTextBlock_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_InventoryPolicyTextBlock_lbl1" xml:lang="en-US" id="us-gaap_InventoryPolicyTextBlock_lbl1">Inventory, Policy [Policy Text Block]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InventoryPolicyTextBlock" xlink:to="us-gaap_InventoryPolicyTextBlock_lbl1" xlink:title="label: InventoryPolicyTextBlock to us-gaap_InventoryPolicyTextBlock_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.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="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_InvestmentTypeCategorizationMember" xlink:label="InvestmentTypeCategorizationMember" xlink:title="InvestmentTypeCategorizationMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InvestmentTypeCategorizationMember_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_InvestmentTypeCategorizationMember_lbl" xml:lang="en-US" id="us-gaap_InvestmentTypeCategorizationMember_lbl">Investments [Domain]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InvestmentTypeCategorizationMember" xlink:to="us-gaap_InvestmentTypeCategorizationMember_lbl" xlink:title="label: InvestmentTypeCategorizationMember to us-gaap_InvestmentTypeCategorizationMember_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_InvestmentIncomeNet" xlink:label="InvestmentIncomeNet" xlink:title="InvestmentIncomeNet" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InvestmentIncomeNet_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_InvestmentIncomeNet_lbl" xml:lang="en-US" id="us-gaap_InvestmentIncomeNet_lbl">Investment income</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InvestmentIncomeNet" xlink:to="us-gaap_InvestmentIncomeNet_lbl" xlink:title="label: InvestmentIncomeNet to us-gaap_InvestmentIncomeNet_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InvestmentIncomeNet_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_InvestmentIncomeNet_lbl1" xml:lang="en-US" id="us-gaap_InvestmentIncomeNet_lbl1">Investment Income, Net</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InvestmentIncomeNet" xlink:to="us-gaap_InvestmentIncomeNet_lbl1" xlink:title="label: InvestmentIncomeNet to us-gaap_InvestmentIncomeNet_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_InvestmentHoldingsLineItems" xlink:label="InvestmentHoldingsLineItems" xlink:title="InvestmentHoldingsLineItems" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InvestmentHoldingsLineItems_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_InvestmentHoldingsLineItems_lbl" xml:lang="en-US" id="us-gaap_InvestmentHoldingsLineItems_lbl">Investment Holdings [Line Items]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InvestmentHoldingsLineItems" xlink:to="us-gaap_InvestmentHoldingsLineItems_lbl" xlink:title="label: InvestmentHoldingsLineItems to us-gaap_InvestmentHoldingsLineItems_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_InvestmentPolicyTextBlock" xlink:label="InvestmentPolicyTextBlock" xlink:title="InvestmentPolicyTextBlock" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InvestmentPolicyTextBlock_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_InvestmentPolicyTextBlock_lbl" xml:lang="en-US" id="us-gaap_InvestmentPolicyTextBlock_lbl">Cash, Cash Equivalents and Investments</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InvestmentPolicyTextBlock" xlink:to="us-gaap_InvestmentPolicyTextBlock_lbl" xlink:title="label: InvestmentPolicyTextBlock to us-gaap_InvestmentPolicyTextBlock_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InvestmentPolicyTextBlock_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_InvestmentPolicyTextBlock_lbl1" xml:lang="en-US" id="us-gaap_InvestmentPolicyTextBlock_lbl1">Investment, Policy [Policy Text Block]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InvestmentPolicyTextBlock" xlink:to="us-gaap_InvestmentPolicyTextBlock_lbl1" xlink:title="label: InvestmentPolicyTextBlock to us-gaap_InvestmentPolicyTextBlock_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_InvestmentTypeAxis" xlink:label="InvestmentTypeAxis" xlink:title="InvestmentTypeAxis" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InvestmentTypeAxis_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_InvestmentTypeAxis_lbl" xml:lang="en-US" id="us-gaap_InvestmentTypeAxis_lbl">Investment Type [Axis]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InvestmentTypeAxis" xlink:to="us-gaap_InvestmentTypeAxis_lbl" xlink:title="label: InvestmentTypeAxis to us-gaap_InvestmentTypeAxis_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_InvestmentHoldingsTable" xlink:label="InvestmentHoldingsTable" xlink:title="InvestmentHoldingsTable" />
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    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_LesseeLeasesPolicyTextBlock" xlink:label="LesseeLeasesPolicyTextBlock" xlink:title="LesseeLeasesPolicyTextBlock" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LesseeLeasesPolicyTextBlock_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_LesseeLeasesPolicyTextBlock_lbl" xml:lang="en-US" id="us-gaap_LesseeLeasesPolicyTextBlock_lbl">Leases</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeLeasesPolicyTextBlock" xlink:to="us-gaap_LesseeLeasesPolicyTextBlock_lbl" xlink:title="label: LesseeLeasesPolicyTextBlock to us-gaap_LesseeLeasesPolicyTextBlock_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LesseeLeasesPolicyTextBlock_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LesseeLeasesPolicyTextBlock_lbl1" xml:lang="en-US" id="us-gaap_LesseeLeasesPolicyTextBlock_lbl1">Lessee, Leases [Policy Text Block]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeLeasesPolicyTextBlock" xlink:to="us-gaap_LesseeLeasesPolicyTextBlock_lbl1" xlink:title="label: LesseeLeasesPolicyTextBlock to us-gaap_LesseeLeasesPolicyTextBlock_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.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">2025</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="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.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">2022</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="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.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">2021</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_lbl" xlink:title="label: LesseeOperatingLeaseLiabilityPaymentsDueNextTwelveMonths to us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueNextTwelveMonths_lbl" />
    <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="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.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/terseLabel" 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="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_LongtermConvertibleDebtCurrentAndNoncurrentAbstract" xlink:label="LongtermConvertibleDebtCurrentAndNoncurrentAbstract" xlink:title="LongtermConvertibleDebtCurrentAndNoncurrentAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LongtermConvertibleDebtCurrentAndNoncurrentAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_LongtermConvertibleDebtCurrentAndNoncurrentAbstract_lbl" xml:lang="en-US" id="us-gaap_LongtermConvertibleDebtCurrentAndNoncurrentAbstract_lbl">Convertible Debt [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LongtermConvertibleDebtCurrentAndNoncurrentAbstract" xlink:to="us-gaap_LongtermConvertibleDebtCurrentAndNoncurrentAbstract_lbl" xlink:title="label: LongtermConvertibleDebtCurrentAndNoncurrentAbstract to us-gaap_LongtermConvertibleDebtCurrentAndNoncurrentAbstract_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LongtermConvertibleDebtCurrentAndNoncurrentAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LongtermConvertibleDebtCurrentAndNoncurrentAbstract_lbl1" xml:lang="en-US" id="us-gaap_LongtermConvertibleDebtCurrentAndNoncurrentAbstract_lbl1">Convertible Debt [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LongtermConvertibleDebtCurrentAndNoncurrentAbstract" xlink:to="us-gaap_LongtermConvertibleDebtCurrentAndNoncurrentAbstract_lbl1" xlink:title="label: LongtermConvertibleDebtCurrentAndNoncurrentAbstract to us-gaap_LongtermConvertibleDebtCurrentAndNoncurrentAbstract_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_LongtermDebtCurrentAndNoncurrentAbstract" xlink:label="LongtermDebtCurrentAndNoncurrentAbstract" xlink:title="LongtermDebtCurrentAndNoncurrentAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LongtermDebtCurrentAndNoncurrentAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LongtermDebtCurrentAndNoncurrentAbstract_lbl" xml:lang="en-US" id="us-gaap_LongtermDebtCurrentAndNoncurrentAbstract_lbl">Long-Term Obligations [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LongtermDebtCurrentAndNoncurrentAbstract" xlink:to="us-gaap_LongtermDebtCurrentAndNoncurrentAbstract_lbl" xlink:title="label: LongtermDebtCurrentAndNoncurrentAbstract to us-gaap_LongtermDebtCurrentAndNoncurrentAbstract_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_LandMember" xlink:label="LandMember" xlink:title="LandMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LandMember_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LandMember_lbl" xml:lang="en-US" id="us-gaap_LandMember_lbl">Land [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LandMember" xlink:to="us-gaap_LandMember_lbl" xlink:title="label: LandMember to us-gaap_LandMember_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.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="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_LeaseholdImprovementsMember" xlink:label="LeaseholdImprovementsMember" xlink:title="LeaseholdImprovementsMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LeaseholdImprovementsMember_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_LeaseholdImprovementsMember_lbl" xml:lang="en-US" id="us-gaap_LeaseholdImprovementsMember_lbl">Leasehold Improvements [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LeaseholdImprovementsMember" xlink:to="us-gaap_LeaseholdImprovementsMember_lbl" xlink:title="label: LeaseholdImprovementsMember to us-gaap_LeaseholdImprovementsMember_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LeaseholdImprovementsMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LeaseholdImprovementsMember_lbl1" xml:lang="en-US" id="us-gaap_LeaseholdImprovementsMember_lbl1">Leasehold Improvements [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LeaseholdImprovementsMember" xlink:to="us-gaap_LeaseholdImprovementsMember_lbl1" xlink:title="label: LeaseholdImprovementsMember to us-gaap_LeaseholdImprovementsMember_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_LegalMattersAndContingenciesTextBlock" xlink:label="LegalMattersAndContingenciesTextBlock" xlink:title="LegalMattersAndContingenciesTextBlock" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LegalMattersAndContingenciesTextBlock_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_LegalMattersAndContingenciesTextBlock_lbl" xml:lang="en-US" id="us-gaap_LegalMattersAndContingenciesTextBlock_lbl">Legal Proceedings</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LegalMattersAndContingenciesTextBlock" xlink:to="us-gaap_LegalMattersAndContingenciesTextBlock_lbl" xlink:title="label: LegalMattersAndContingenciesTextBlock to us-gaap_LegalMattersAndContingenciesTextBlock_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LegalMattersAndContingenciesTextBlock_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LegalMattersAndContingenciesTextBlock_lbl1" xml:lang="en-US" id="us-gaap_LegalMattersAndContingenciesTextBlock_lbl1">Legal Matters and Contingencies [Text Block]</link:label>
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    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.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>
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    <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="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_LiabilitiesAndStockholdersEquityAbstract" xlink:label="LiabilitiesAndStockholdersEquityAbstract" xlink:title="LiabilitiesAndStockholdersEquityAbstract" />
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    <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" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_Liabilities_lbl" xlink:role="http://www.xbrl.org/2003/role/totalLabel" xlink:title="us-gaap_Liabilities_lbl" xml:lang="en-US" id="us-gaap_Liabilities_lbl">Total liabilities</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="Liabilities" xlink:to="us-gaap_Liabilities_lbl" xlink:title="label: Liabilities to us-gaap_Liabilities_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_Liabilities_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_Liabilities_lbl1" xml:lang="en-US" id="us-gaap_Liabilities_lbl1">Liabilities</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="Liabilities" xlink:to="us-gaap_Liabilities_lbl1" xlink:title="label: Liabilities to us-gaap_Liabilities_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.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>
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    <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="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.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="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_LineOfCreditFacilityTable" xlink:label="LineOfCreditFacilityTable" xlink:title="LineOfCreditFacilityTable" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LineOfCreditFacilityTable_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LineOfCreditFacilityTable_lbl" xml:lang="en-US" id="us-gaap_LineOfCreditFacilityTable_lbl">Line of Credit Facility [Table]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LineOfCreditFacilityTable" xlink:to="us-gaap_LineOfCreditFacilityTable_lbl" xlink:title="label: LineOfCreditFacilityTable to us-gaap_LineOfCreditFacilityTable_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_LineOfCreditFacilityLineItems" xlink:label="LineOfCreditFacilityLineItems" xlink:title="LineOfCreditFacilityLineItems" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LineOfCreditFacilityLineItems_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LineOfCreditFacilityLineItems_lbl" xml:lang="en-US" id="us-gaap_LineOfCreditFacilityLineItems_lbl">Line of Credit Facility [Line Items]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LineOfCreditFacilityLineItems" xlink:to="us-gaap_LineOfCreditFacilityLineItems_lbl" xlink:title="label: LineOfCreditFacilityLineItems to us-gaap_LineOfCreditFacilityLineItems_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_LineOfCreditFacilityAbstract" xlink:label="LineOfCreditFacilityAbstract" xlink:title="LineOfCreditFacilityAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LineOfCreditFacilityAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_LineOfCreditFacilityAbstract_lbl" xml:lang="en-US" id="us-gaap_LineOfCreditFacilityAbstract_lbl">Line of Credit Arrangement [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LineOfCreditFacilityAbstract" xlink:to="us-gaap_LineOfCreditFacilityAbstract_lbl" xlink:title="label: LineOfCreditFacilityAbstract to us-gaap_LineOfCreditFacilityAbstract_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LineOfCreditFacilityAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LineOfCreditFacilityAbstract_lbl1" xml:lang="en-US" id="us-gaap_LineOfCreditFacilityAbstract_lbl1">Line of Credit Facility [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LineOfCreditFacilityAbstract" xlink:to="us-gaap_LineOfCreditFacilityAbstract_lbl1" xlink:title="label: LineOfCreditFacilityAbstract to us-gaap_LineOfCreditFacilityAbstract_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_LineOfCreditFacilityAxis" xlink:label="LineOfCreditFacilityAxis" xlink:title="LineOfCreditFacilityAxis" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LineOfCreditFacilityAxis_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LineOfCreditFacilityAxis_lbl" xml:lang="en-US" id="us-gaap_LineOfCreditFacilityAxis_lbl">Lender Name [Axis]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LineOfCreditFacilityAxis" xlink:to="us-gaap_LineOfCreditFacilityAxis_lbl" xlink:title="label: LineOfCreditFacilityAxis to us-gaap_LineOfCreditFacilityAxis_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_LineOfCreditFacilityMaximumBorrowingCapacity" xlink:label="LineOfCreditFacilityMaximumBorrowingCapacity" xlink:title="LineOfCreditFacilityMaximumBorrowingCapacity" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LineOfCreditFacilityMaximumBorrowingCapacity_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LineOfCreditFacilityMaximumBorrowingCapacity_lbl" xml:lang="en-US" id="us-gaap_LineOfCreditFacilityMaximumBorrowingCapacity_lbl">Maximum borrowing capacity</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LineOfCreditFacilityMaximumBorrowingCapacity" xlink:to="us-gaap_LineOfCreditFacilityMaximumBorrowingCapacity_lbl" xlink:title="label: LineOfCreditFacilityMaximumBorrowingCapacity to us-gaap_LineOfCreditFacilityMaximumBorrowingCapacity_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_LineOfCreditFacilityLenderDomain" xlink:label="LineOfCreditFacilityLenderDomain" xlink:title="LineOfCreditFacilityLenderDomain" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LineOfCreditFacilityLenderDomain_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LineOfCreditFacilityLenderDomain_lbl" xml:lang="en-US" id="us-gaap_LineOfCreditFacilityLenderDomain_lbl">Line of Credit Facility, Lender [Domain]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LineOfCreditFacilityLenderDomain" xlink:to="us-gaap_LineOfCreditFacilityLenderDomain_lbl" xlink:title="label: LineOfCreditFacilityLenderDomain to us-gaap_LineOfCreditFacilityLenderDomain_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_LitigationSettlementAmountAwardedFromOtherParty" xlink:label="LitigationSettlementAmountAwardedFromOtherParty" xlink:title="LitigationSettlementAmountAwardedFromOtherParty" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LitigationSettlementAmountAwardedFromOtherParty_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_LitigationSettlementAmountAwardedFromOtherParty_lbl" xml:lang="en-US" id="us-gaap_LitigationSettlementAmountAwardedFromOtherParty_lbl">Award from arbitration panel</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LitigationSettlementAmountAwardedFromOtherParty" xlink:to="us-gaap_LitigationSettlementAmountAwardedFromOtherParty_lbl" xlink:title="label: LitigationSettlementAmountAwardedFromOtherParty to us-gaap_LitigationSettlementAmountAwardedFromOtherParty_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LitigationSettlementAmountAwardedFromOtherParty_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LitigationSettlementAmountAwardedFromOtherParty_lbl1" xml:lang="en-US" id="us-gaap_LitigationSettlementAmountAwardedFromOtherParty_lbl1">Litigation Settlement, Amount Awarded from Other Party</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LitigationSettlementAmountAwardedFromOtherParty" xlink:to="us-gaap_LitigationSettlementAmountAwardedFromOtherParty_lbl1" xlink:title="label: LitigationSettlementAmountAwardedFromOtherParty to us-gaap_LitigationSettlementAmountAwardedFromOtherParty_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.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">Long-term mortgage debt</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LoansPayableToBank" xlink:to="us-gaap_LoansPayableToBank_lbl" xlink:title="label: LoansPayableToBank to us-gaap_LoansPayableToBank_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LoansPayableToBank_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LoansPayableToBank_lbl1" xml:lang="en-US" id="us-gaap_LoansPayableToBank_lbl1">Loans Payable to Bank</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LoansPayableToBank" xlink:to="us-gaap_LoansPayableToBank_lbl1" xlink:title="label: LoansPayableToBank to us-gaap_LoansPayableToBank_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_LongTermDebtFairValue" xlink:label="LongTermDebtFairValue" xlink:title="LongTermDebtFairValue" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LongTermDebtFairValue_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LongTermDebtFairValue_lbl" xml:lang="en-US" id="us-gaap_LongTermDebtFairValue_lbl">Fair value of outstanding notes</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LongTermDebtFairValue" xlink:to="us-gaap_LongTermDebtFairValue_lbl" xlink:title="label: LongTermDebtFairValue to us-gaap_LongTermDebtFairValue_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_LongTermDebtAndCapitalLeaseObligationsCurrent" xlink:label="LongTermDebtAndCapitalLeaseObligationsCurrent" xlink:title="LongTermDebtAndCapitalLeaseObligationsCurrent" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LongTermDebtAndCapitalLeaseObligationsCurrent_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LongTermDebtAndCapitalLeaseObligationsCurrent_lbl" xml:lang="en-US" id="us-gaap_LongTermDebtAndCapitalLeaseObligationsCurrent_lbl">LongTermDebtAndCapitalLeaseObligationsCurrent</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LongTermDebtAndCapitalLeaseObligationsCurrent" xlink:to="us-gaap_LongTermDebtAndCapitalLeaseObligationsCurrent_lbl" xlink:title="label: LongTermDebtAndCapitalLeaseObligationsCurrent to us-gaap_LongTermDebtAndCapitalLeaseObligationsCurrent_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LongTermDebtAndCapitalLeaseObligationsCurrent_lbl1" xlink:role="http://www.xbrl.org/2009/role/negatedLabel" xlink:title="us-gaap_LongTermDebtAndCapitalLeaseObligationsCurrent_lbl1" xml:lang="en-US" id="us-gaap_LongTermDebtAndCapitalLeaseObligationsCurrent_lbl1">Less: current portion</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LongTermDebtAndCapitalLeaseObligationsCurrent" xlink:to="us-gaap_LongTermDebtAndCapitalLeaseObligationsCurrent_lbl1" xlink:title="label: LongTermDebtAndCapitalLeaseObligationsCurrent to us-gaap_LongTermDebtAndCapitalLeaseObligationsCurrent_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_LongTermDebtAndCapitalLeaseObligations" xlink:label="LongTermDebtAndCapitalLeaseObligations" xlink:title="LongTermDebtAndCapitalLeaseObligations" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LongTermDebtAndCapitalLeaseObligations_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_LongTermDebtAndCapitalLeaseObligations_lbl" xml:lang="en-US" id="us-gaap_LongTermDebtAndCapitalLeaseObligations_lbl">Total Long-Term Obligations</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LongTermDebtAndCapitalLeaseObligations" xlink:to="us-gaap_LongTermDebtAndCapitalLeaseObligations_lbl" xlink:title="label: LongTermDebtAndCapitalLeaseObligations to us-gaap_LongTermDebtAndCapitalLeaseObligations_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LongTermDebtAndCapitalLeaseObligations_lbl1" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="us-gaap_LongTermDebtAndCapitalLeaseObligations_lbl1" xml:lang="en-US" id="us-gaap_LongTermDebtAndCapitalLeaseObligations_lbl1">Total long-term debt</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LongTermDebtAndCapitalLeaseObligations" xlink:to="us-gaap_LongTermDebtAndCapitalLeaseObligations_lbl1" xlink:title="label: LongTermDebtAndCapitalLeaseObligations to us-gaap_LongTermDebtAndCapitalLeaseObligations_lbl1" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LongTermDebtAndCapitalLeaseObligations_lbl2" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LongTermDebtAndCapitalLeaseObligations_lbl2" xml:lang="en-US" id="us-gaap_LongTermDebtAndCapitalLeaseObligations_lbl2">Long-term Debt and Lease Obligation</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LongTermDebtAndCapitalLeaseObligations" xlink:to="us-gaap_LongTermDebtAndCapitalLeaseObligations_lbl2" xlink:title="label: LongTermDebtAndCapitalLeaseObligations to us-gaap_LongTermDebtAndCapitalLeaseObligations_lbl2" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_LongTermLoansFromBank" xlink:label="LongTermLoansFromBank" xlink:title="LongTermLoansFromBank" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LongTermLoansFromBank_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LongTermLoansFromBank_lbl" xml:lang="en-US" id="us-gaap_LongTermLoansFromBank_lbl">Long-term mortgage debt</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LongTermLoansFromBank" xlink:to="us-gaap_LongTermLoansFromBank_lbl" xlink:title="label: LongTermLoansFromBank to us-gaap_LongTermLoansFromBank_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.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="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_MaturitiesOfLongtermDebtAndCapitalLeaseObligationsAbstract" xlink:label="MaturitiesOfLongtermDebtAndCapitalLeaseObligationsAbstract" xlink:title="MaturitiesOfLongtermDebtAndCapitalLeaseObligationsAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_MaturitiesOfLongtermDebtAndCapitalLeaseObligationsAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_MaturitiesOfLongtermDebtAndCapitalLeaseObligationsAbstract_lbl" xml:lang="en-US" id="us-gaap_MaturitiesOfLongtermDebtAndCapitalLeaseObligationsAbstract_lbl">Annual Debt and Other Obligation Maturities [Abstract]</link:label>
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    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_MeasurementInputTypeDomain" xlink:label="MeasurementInputTypeDomain" xlink:title="MeasurementInputTypeDomain" />
    <link:label xlink:type="resource" xlink:label="us-gaap_MeasurementInputTypeDomain_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_MeasurementInputTypeDomain_lbl" xml:lang="en-US" id="us-gaap_MeasurementInputTypeDomain_lbl">Measurement Input Type [Domain]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MeasurementInputTypeDomain" xlink:to="us-gaap_MeasurementInputTypeDomain_lbl" xlink:title="label: MeasurementInputTypeDomain to us-gaap_MeasurementInputTypeDomain_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_MeasurementInputTypeAxis" xlink:label="MeasurementInputTypeAxis" xlink:title="MeasurementInputTypeAxis" />
    <link:label xlink:type="resource" xlink:label="us-gaap_MeasurementInputTypeAxis_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_MeasurementInputTypeAxis_lbl" xml:lang="en-US" id="us-gaap_MeasurementInputTypeAxis_lbl">Measurement Input Type [Axis]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MeasurementInputTypeAxis" xlink:to="us-gaap_MeasurementInputTypeAxis_lbl" xlink:title="label: MeasurementInputTypeAxis to us-gaap_MeasurementInputTypeAxis_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_MeasurementInputDiscountRateMember" xlink:label="MeasurementInputDiscountRateMember" xlink:title="MeasurementInputDiscountRateMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_MeasurementInputDiscountRateMember_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_MeasurementInputDiscountRateMember_lbl" xml:lang="en-US" id="us-gaap_MeasurementInputDiscountRateMember_lbl">Borrowing Rate [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MeasurementInputDiscountRateMember" xlink:to="us-gaap_MeasurementInputDiscountRateMember_lbl" xlink:title="label: MeasurementInputDiscountRateMember to us-gaap_MeasurementInputDiscountRateMember_lbl" />
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    <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">Impact of Recently Issued Accounting Standards</link:label>
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    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_NonoperatingIncomeExpenseAbstract" xlink:label="NonoperatingIncomeExpenseAbstract" xlink:title="NonoperatingIncomeExpenseAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_NonoperatingIncomeExpenseAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_NonoperatingIncomeExpenseAbstract_lbl" xml:lang="en-US" id="us-gaap_NonoperatingIncomeExpenseAbstract_lbl">Other income (expense):</link:label>
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    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_NotesReduction" xlink:label="NotesReduction" xlink:title="NotesReduction" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_PaymentsForHedgeFinancingActivities_lbl1" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_PaymentsForHedgeFinancingActivities_lbl1" xml:lang="en-US" id="us-gaap_PaymentsForHedgeFinancingActivities_lbl1">Purchase of note hedges</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_PaymentsForHedgeFinancingActivities_lbl2" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_PaymentsForHedgeFinancingActivities_lbl2" xml:lang="en-US" id="us-gaap_PaymentsForHedgeFinancingActivities_lbl2">Payments for Hedge, Financing Activities</link:label>
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    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_PaymentsForRepurchaseOfCommonStock" xlink:label="PaymentsForRepurchaseOfCommonStock" xlink:title="PaymentsForRepurchaseOfCommonStock" />
    <link:label xlink:type="resource" xlink:label="us-gaap_PaymentsForRepurchaseOfCommonStock_lbl" xlink:role="http://www.xbrl.org/2009/role/negatedLabel" xlink:title="us-gaap_PaymentsForRepurchaseOfCommonStock_lbl" xml:lang="en-US" id="us-gaap_PaymentsForRepurchaseOfCommonStock_lbl">Repurchases and retirements of common stock</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_PaymentsForRepurchaseOfCommonStock_lbl1" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_PaymentsForRepurchaseOfCommonStock_lbl1" xml:lang="en-US" id="us-gaap_PaymentsForRepurchaseOfCommonStock_lbl1">Shares repurchased</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_PaymentsForRepurchaseOfCommonStock_lbl2" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_PaymentsForRepurchaseOfCommonStock_lbl2" xml:lang="en-US" id="us-gaap_PaymentsForRepurchaseOfCommonStock_lbl2">Payments for Repurchase of Common Stock</link:label>
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    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_PaymentsToAcquireBuildings" xlink:label="PaymentsToAcquireBuildings" xlink:title="PaymentsToAcquireBuildings" />
    <link:label xlink:type="resource" xlink:label="us-gaap_PaymentsToAcquireBuildings_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_PaymentsToAcquireBuildings_lbl" xml:lang="en-US" id="us-gaap_PaymentsToAcquireBuildings_lbl">Payment to acquire building</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PaymentsToAcquireBuildings" xlink:to="us-gaap_PaymentsToAcquireBuildings_lbl" xlink:title="label: PaymentsToAcquireBuildings to us-gaap_PaymentsToAcquireBuildings_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_PaymentsForRestructuring" xlink:label="PaymentsForRestructuring" xlink:title="PaymentsForRestructuring" />
    <link:label xlink:type="resource" xlink:label="us-gaap_PaymentsForRestructuring_lbl" xlink:role="http://www.xbrl.org/2009/role/negatedLabel" xlink:title="us-gaap_PaymentsForRestructuring_lbl" xml:lang="en-US" id="us-gaap_PaymentsForRestructuring_lbl">Amounts paid during the period</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_PaymentsForRestructuring_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_PaymentsForRestructuring_lbl1" xml:lang="en-US" id="us-gaap_PaymentsForRestructuring_lbl1">Payments for Restructuring</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PaymentsForRestructuring" xlink:to="us-gaap_PaymentsForRestructuring_lbl1" xlink:title="label: PaymentsForRestructuring to us-gaap_PaymentsForRestructuring_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_PaymentsToAcquireAvailableForSaleSecuritiesDebt" xlink:label="PaymentsToAcquireAvailableForSaleSecuritiesDebt" xlink:title="PaymentsToAcquireAvailableForSaleSecuritiesDebt" />
    <link:label xlink:type="resource" xlink:label="us-gaap_PaymentsToAcquireAvailableForSaleSecuritiesDebt_lbl" xlink:role="http://www.xbrl.org/2009/role/negatedLabel" xlink:title="us-gaap_PaymentsToAcquireAvailableForSaleSecuritiesDebt_lbl" xml:lang="en-US" id="us-gaap_PaymentsToAcquireAvailableForSaleSecuritiesDebt_lbl">Purchases of short-term investments</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_PaymentsToAcquireAvailableForSaleSecuritiesDebt_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_PaymentsToAcquireAvailableForSaleSecuritiesDebt_lbl1" xml:lang="en-US" id="us-gaap_PaymentsToAcquireAvailableForSaleSecuritiesDebt_lbl1">Payments to Acquire Debt Securities, Available-for-sale</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PaymentsToAcquireAvailableForSaleSecuritiesDebt" xlink:to="us-gaap_PaymentsToAcquireAvailableForSaleSecuritiesDebt_lbl1" xlink:title="label: PaymentsToAcquireAvailableForSaleSecuritiesDebt to us-gaap_PaymentsToAcquireAvailableForSaleSecuritiesDebt_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_PaymentsOfDebtIssuanceCosts" xlink:label="PaymentsOfDebtIssuanceCosts" xlink:title="PaymentsOfDebtIssuanceCosts" />
    <link:label xlink:type="resource" xlink:label="us-gaap_PaymentsOfDebtIssuanceCosts_lbl" xlink:role="http://www.xbrl.org/2009/role/negatedLabel" xlink:title="us-gaap_PaymentsOfDebtIssuanceCosts_lbl" xml:lang="en-US" id="us-gaap_PaymentsOfDebtIssuanceCosts_lbl">0.125 percent convertible senior notes issuance costs</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_PaymentsOfDebtIssuanceCosts_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_PaymentsOfDebtIssuanceCosts_lbl1" xml:lang="en-US" id="us-gaap_PaymentsOfDebtIssuanceCosts_lbl1">Payments of Debt Issuance Costs</link:label>
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    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_PaymentsToAcquireOtherProductiveAssets" xlink:label="PaymentsToAcquireOtherProductiveAssets" xlink:title="PaymentsToAcquireOtherProductiveAssets" />
    <link:label xlink:type="resource" xlink:label="us-gaap_PaymentsToAcquireOtherProductiveAssets_lbl" xlink:role="http://www.xbrl.org/2009/role/negatedLabel" xlink:title="us-gaap_PaymentsToAcquireOtherProductiveAssets_lbl" xml:lang="en-US" id="us-gaap_PaymentsToAcquireOtherProductiveAssets_lbl">Acquisition of licenses and other assets, net</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PaymentsToAcquireOtherProductiveAssets" xlink:to="us-gaap_PaymentsToAcquireOtherProductiveAssets_lbl" xlink:title="label: PaymentsToAcquireOtherProductiveAssets to us-gaap_PaymentsToAcquireOtherProductiveAssets_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_PaymentsToAcquireOtherProductiveAssets_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_PaymentsToAcquireOtherProductiveAssets_lbl1" xml:lang="en-US" id="us-gaap_PaymentsToAcquireOtherProductiveAssets_lbl1">Payments to Acquire Other Productive Assets</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PaymentsToAcquireOtherProductiveAssets" xlink:to="us-gaap_PaymentsToAcquireOtherProductiveAssets_lbl1" xlink:title="label: PaymentsToAcquireOtherProductiveAssets to us-gaap_PaymentsToAcquireOtherProductiveAssets_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.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">Purchase of strategic investments</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PaymentsToAcquireOtherInvestments" xlink:to="us-gaap_PaymentsToAcquireOtherInvestments_lbl" xlink:title="label: PaymentsToAcquireOtherInvestments to us-gaap_PaymentsToAcquireOtherInvestments_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_PaymentsToAcquireOtherInvestments_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_PaymentsToAcquireOtherInvestments_lbl1" xml:lang="en-US" id="us-gaap_PaymentsToAcquireOtherInvestments_lbl1">Payments to Acquire Other Investments</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PaymentsToAcquireOtherInvestments" xlink:to="us-gaap_PaymentsToAcquireOtherInvestments_lbl1" xlink:title="label: PaymentsToAcquireOtherInvestments to us-gaap_PaymentsToAcquireOtherInvestments_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_PaymentsToAcquirePropertyPlantAndEquipment" xlink:label="PaymentsToAcquirePropertyPlantAndEquipment" xlink:title="PaymentsToAcquirePropertyPlantAndEquipment" />
    <link:label xlink:type="resource" xlink:label="us-gaap_PaymentsToAcquirePropertyPlantAndEquipment_lbl" xlink:role="http://www.xbrl.org/2009/role/negatedLabel" xlink:title="us-gaap_PaymentsToAcquirePropertyPlantAndEquipment_lbl" xml:lang="en-US" id="us-gaap_PaymentsToAcquirePropertyPlantAndEquipment_lbl">Purchases of property, plant and equipment</link:label>
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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>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PaymentsToAcquirePropertyPlantAndEquipment" xlink:to="us-gaap_PaymentsToAcquirePropertyPlantAndEquipment_lbl1" xlink:title="label: PaymentsToAcquirePropertyPlantAndEquipment to us-gaap_PaymentsToAcquirePropertyPlantAndEquipment_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_PaymentsToMinorityShareholders" xlink:label="PaymentsToMinorityShareholders" xlink:title="PaymentsToMinorityShareholders" />
    <link:label xlink:type="resource" xlink:label="us-gaap_PaymentsToMinorityShareholders_lbl" xlink:role="http://www.xbrl.org/2009/role/negatedLabel" xlink:title="us-gaap_PaymentsToMinorityShareholders_lbl" xml:lang="en-US" id="us-gaap_PaymentsToMinorityShareholders_lbl">Purchase of noncontrolling interest of Akcea Therapeutics, Inc., including cash payments for cancellation of Akcea Therapeutics, Inc. equity awards</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PaymentsToMinorityShareholders" xlink:to="us-gaap_PaymentsToMinorityShareholders_lbl" xlink:title="label: PaymentsToMinorityShareholders to us-gaap_PaymentsToMinorityShareholders_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_PaymentsToMinorityShareholders_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_PaymentsToMinorityShareholders_lbl1" xml:lang="en-US" id="us-gaap_PaymentsToMinorityShareholders_lbl1">Payments to Noncontrolling Interests</link:label>
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    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_PaymentsToAcquirePropertyPlantAndEquipmentAbstract" xlink:label="PaymentsToAcquirePropertyPlantAndEquipmentAbstract" xlink:title="PaymentsToAcquirePropertyPlantAndEquipmentAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_PaymentsToAcquirePropertyPlantAndEquipmentAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_PaymentsToAcquirePropertyPlantAndEquipmentAbstract_lbl" xml:lang="en-US" id="us-gaap_PaymentsToAcquirePropertyPlantAndEquipmentAbstract_lbl">Research and Development and Manufacturing Facilities [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PaymentsToAcquirePropertyPlantAndEquipmentAbstract" xlink:to="us-gaap_PaymentsToAcquirePropertyPlantAndEquipmentAbstract_lbl" xlink:title="label: PaymentsToAcquirePropertyPlantAndEquipmentAbstract to us-gaap_PaymentsToAcquirePropertyPlantAndEquipmentAbstract_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_PensionAndOtherPostretirementBenefitsDisclosureTextBlock" xlink:label="PensionAndOtherPostretirementBenefitsDisclosureTextBlock" xlink:title="PensionAndOtherPostretirementBenefitsDisclosureTextBlock" />
    <link:label xlink:type="resource" xlink:label="us-gaap_PensionAndOtherPostretirementBenefitsDisclosureTextBlock_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_PensionAndOtherPostretirementBenefitsDisclosureTextBlock_lbl" xml:lang="en-US" id="us-gaap_PensionAndOtherPostretirementBenefitsDisclosureTextBlock_lbl">Employment Benefits</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PensionAndOtherPostretirementBenefitsDisclosureTextBlock" xlink:to="us-gaap_PensionAndOtherPostretirementBenefitsDisclosureTextBlock_lbl" xlink:title="label: PensionAndOtherPostretirementBenefitsDisclosureTextBlock to us-gaap_PensionAndOtherPostretirementBenefitsDisclosureTextBlock_lbl" />
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PensionAndOtherPostretirementBenefitsDisclosureTextBlock" xlink:to="us-gaap_PensionAndOtherPostretirementBenefitsDisclosureTextBlock_lbl1" xlink:title="label: PensionAndOtherPostretirementBenefitsDisclosureTextBlock to us-gaap_PensionAndOtherPostretirementBenefitsDisclosureTextBlock_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_PlanNameAxis" xlink:label="PlanNameAxis" xlink:title="PlanNameAxis" />
    <link:label xlink:type="resource" xlink:label="us-gaap_PlanNameAxis_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_PlanNameAxis_lbl" xml:lang="en-US" id="us-gaap_PlanNameAxis_lbl">Plan Name [Axis]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PlanNameAxis" xlink:to="us-gaap_PlanNameAxis_lbl" xlink:title="label: PlanNameAxis to us-gaap_PlanNameAxis_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_PlanNameDomain" xlink:label="PlanNameDomain" xlink:title="PlanNameDomain" />
    <link:label xlink:type="resource" xlink:label="us-gaap_PlanNameDomain_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_PlanNameDomain_lbl" xml:lang="en-US" id="us-gaap_PlanNameDomain_lbl">Plan Name [Domain]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PlanNameDomain" xlink:to="us-gaap_PlanNameDomain_lbl" xlink:title="label: PlanNameDomain to us-gaap_PlanNameDomain_lbl" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_PreferredStockMember_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_PreferredStockMember_lbl" xml:lang="en-US" id="us-gaap_PreferredStockMember_lbl">Preferred Stock [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PreferredStockMember" xlink:to="us-gaap_PreferredStockMember_lbl" xlink:title="label: PreferredStockMember to us-gaap_PreferredStockMember_lbl" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_PropertyPlantAndEquipmentAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_PropertyPlantAndEquipmentAbstract_lbl" xml:lang="en-US" id="us-gaap_PropertyPlantAndEquipmentAbstract_lbl">Property, Plant and Equipment [Abstract]</link:label>
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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_PropertyPlantAndEquipmentTypeDomain_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_PropertyPlantAndEquipmentTypeDomain_lbl" xml:lang="en-US" id="us-gaap_PropertyPlantAndEquipmentTypeDomain_lbl">Property, Plant and Equipment, Type [Domain]</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_PropertyPlantAndEquipmentGross_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_PropertyPlantAndEquipmentGross_lbl" xml:lang="en-US" id="us-gaap_PropertyPlantAndEquipmentGross_lbl">Property, plant and equipment</link:label>
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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_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber_lbl2" xml:lang="en-US" id="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber_lbl2">Number of options outstanding (in shares)</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber_lbl3" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber_lbl3" xml:lang="en-US" id="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber_lbl3">Share-based Compensation Arrangement by Share-based Payment Award, Options, Outstanding, Number</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber_lbl3" xlink:title="label: ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber to us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber_lbl3" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePrice" xlink:label="ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePrice" xlink:title="ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePrice" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePrice_lbl" xlink:role="http://www.xbrl.org/2003/role/periodEndLabel" xlink:title="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePrice_lbl" xml:lang="en-US" id="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePrice_lbl">Outstanding at end of period (in dollars per share)</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePrice" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePrice_lbl" xlink:title="label: ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePrice to us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePrice_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePrice_lbl1" xlink:role="http://www.xbrl.org/2003/role/periodStartLabel" xlink:title="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePrice_lbl1" xml:lang="en-US" id="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePrice_lbl1">Outstanding at beginning of period (in dollars per share)</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePrice" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePrice_lbl1" xlink:title="label: ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePrice to us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePrice_lbl1" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePrice_lbl2" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePrice_lbl2" xml:lang="en-US" id="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePrice_lbl2">Share-based Compensation Arrangement by Share-based Payment Award, Options, Outstanding, Weighted Average Exercise Price</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePrice" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePrice_lbl2" xlink:title="label: ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePrice to us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePrice_lbl2" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingIntrinsicValue" xlink:label="ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingIntrinsicValue" xlink:title="ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingIntrinsicValue" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingIntrinsicValue_lbl" xlink:role="http://www.xbrl.org/2003/role/periodEndLabel" xlink:title="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingIntrinsicValue_lbl" xml:lang="en-US" id="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingIntrinsicValue_lbl">Aggregate intrinsic value, outstanding at end of period</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingIntrinsicValue" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingIntrinsicValue_lbl" xlink:title="label: ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingIntrinsicValue to us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingIntrinsicValue_lbl" />
    <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>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingIntrinsicValue" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingIntrinsicValue_lbl1" xlink:title="label: ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingIntrinsicValue to us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingIntrinsicValue_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingRollForward" xlink:label="ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingRollForward" xlink:title="ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingRollForward" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingRollForward_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingRollForward_lbl" xml:lang="en-US" id="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingRollForward_lbl">Number of Shares [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingRollForward" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingRollForward_lbl" xlink:title="label: ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingRollForward to us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingRollForward_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingRollForward_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingRollForward_lbl1" xml:lang="en-US" id="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingRollForward_lbl1">Share-based Compensation Arrangement by Share-based Payment Award, Options, Outstanding [Roll Forward]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingRollForward" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingRollForward_lbl1" xlink:title="label: ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingRollForward to us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingRollForward_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.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>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SharesIssued" xlink:to="us-gaap_SharesIssued_lbl2" xlink:title="label: SharesIssued to us-gaap_SharesIssued_lbl2" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_SharesPaidForTaxWithholdingForShareBasedCompensation" xlink:label="SharesPaidForTaxWithholdingForShareBasedCompensation" xlink:title="SharesPaidForTaxWithholdingForShareBasedCompensation" />
    <link:label xlink:type="resource" xlink:label="us-gaap_SharesPaidForTaxWithholdingForShareBasedCompensation_lbl" xlink:role="http://www.xbrl.org/2009/role/negatedLabel" xlink:title="us-gaap_SharesPaidForTaxWithholdingForShareBasedCompensation_lbl" xml:lang="en-US" id="us-gaap_SharesPaidForTaxWithholdingForShareBasedCompensation_lbl">Payments of tax withholdings related to vesting of employee stock awards and exercise of employee stock options (in shares)</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SharesPaidForTaxWithholdingForShareBasedCompensation" xlink:to="us-gaap_SharesPaidForTaxWithholdingForShareBasedCompensation_lbl" xlink:title="label: SharesPaidForTaxWithholdingForShareBasedCompensation to us-gaap_SharesPaidForTaxWithholdingForShareBasedCompensation_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_SharesPaidForTaxWithholdingForShareBasedCompensation_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_SharesPaidForTaxWithholdingForShareBasedCompensation_lbl1" xml:lang="en-US" id="us-gaap_SharesPaidForTaxWithholdingForShareBasedCompensation_lbl1">Share-based Payment Arrangement, Shares Withheld for Tax Withholding Obligation</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SharesPaidForTaxWithholdingForShareBasedCompensation" xlink:to="us-gaap_SharesPaidForTaxWithholdingForShareBasedCompensation_lbl1" xlink:title="label: SharesPaidForTaxWithholdingForShareBasedCompensation to us-gaap_SharesPaidForTaxWithholdingForShareBasedCompensation_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_StatementOfFinancialPositionAbstract" xlink:label="StatementOfFinancialPositionAbstract" xlink:title="StatementOfFinancialPositionAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_StatementOfFinancialPositionAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_StatementOfFinancialPositionAbstract_lbl" xml:lang="en-US" id="us-gaap_StatementOfFinancialPositionAbstract_lbl">CONSOLIDATED BALANCE SHEETS [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StatementOfFinancialPositionAbstract" xlink:to="us-gaap_StatementOfFinancialPositionAbstract_lbl" xlink:title="label: StatementOfFinancialPositionAbstract to us-gaap_StatementOfFinancialPositionAbstract_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_StatementOfIncomeAndComprehensiveIncomeAbstract" xlink:label="StatementOfIncomeAndComprehensiveIncomeAbstract" xlink:title="StatementOfIncomeAndComprehensiveIncomeAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_StatementOfIncomeAndComprehensiveIncomeAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_StatementOfIncomeAndComprehensiveIncomeAbstract_lbl" xml:lang="en-US" id="us-gaap_StatementOfIncomeAndComprehensiveIncomeAbstract_lbl">CONSOLIDATED STATEMENTS OF COMPREHENSIVE INCOME (LOSS) [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StatementOfIncomeAndComprehensiveIncomeAbstract" xlink:to="us-gaap_StatementOfIncomeAndComprehensiveIncomeAbstract_lbl" xlink:title="label: StatementOfIncomeAndComprehensiveIncomeAbstract to us-gaap_StatementOfIncomeAndComprehensiveIncomeAbstract_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_StatementTable" xlink:label="StatementTable" xlink:title="StatementTable" />
    <link:label xlink:type="resource" xlink:label="us-gaap_StatementTable_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_StatementTable_lbl" xml:lang="en-US" id="us-gaap_StatementTable_lbl">Statement [Table]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StatementTable" xlink:to="us-gaap_StatementTable_lbl" xlink:title="label: StatementTable to us-gaap_StatementTable_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_StatementBusinessSegmentsAxis" xlink:label="StatementBusinessSegmentsAxis" xlink:title="StatementBusinessSegmentsAxis" />
    <link:label xlink:type="resource" xlink:label="us-gaap_StatementBusinessSegmentsAxis_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_StatementBusinessSegmentsAxis_lbl" xml:lang="en-US" id="us-gaap_StatementBusinessSegmentsAxis_lbl">Segments [Axis]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StatementBusinessSegmentsAxis" xlink:to="us-gaap_StatementBusinessSegmentsAxis_lbl" xlink:title="label: StatementBusinessSegmentsAxis to us-gaap_StatementBusinessSegmentsAxis_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_StatementLineItems" xlink:label="StatementLineItems" xlink:title="StatementLineItems" />
    <link:label xlink:type="resource" xlink:label="us-gaap_StatementLineItems_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_StatementLineItems_lbl" xml:lang="en-US" id="us-gaap_StatementLineItems_lbl">Statement [Line Items]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StatementLineItems" xlink:to="us-gaap_StatementLineItems_lbl" xlink:title="label: StatementLineItems to us-gaap_StatementLineItems_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_StatementOfCashFlowsAbstract" xlink:label="StatementOfCashFlowsAbstract" xlink:title="StatementOfCashFlowsAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_StatementOfCashFlowsAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_StatementOfCashFlowsAbstract_lbl" xml:lang="en-US" id="us-gaap_StatementOfCashFlowsAbstract_lbl">CONSOLIDATED STATEMENTS OF CASH FLOWS [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StatementOfCashFlowsAbstract" xlink:to="us-gaap_StatementOfCashFlowsAbstract_lbl" xlink:title="label: StatementOfCashFlowsAbstract to us-gaap_StatementOfCashFlowsAbstract_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_StatementEquityComponentsAxis" xlink:label="StatementEquityComponentsAxis" xlink:title="StatementEquityComponentsAxis" />
    <link:label xlink:type="resource" xlink:label="us-gaap_StatementEquityComponentsAxis_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_StatementEquityComponentsAxis_lbl" xml:lang="en-US" id="us-gaap_StatementEquityComponentsAxis_lbl">Equity Components [Axis]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StatementEquityComponentsAxis" xlink:to="us-gaap_StatementEquityComponentsAxis_lbl" xlink:title="label: StatementEquityComponentsAxis to us-gaap_StatementEquityComponentsAxis_lbl" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_StatementClassOfStockAxis_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_StatementClassOfStockAxis_lbl" xml:lang="en-US" id="us-gaap_StatementClassOfStockAxis_lbl">Class of Stock [Axis]</link:label>
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    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_StatementOfStockholdersEquityAbstract" xlink:label="StatementOfStockholdersEquityAbstract" xlink:title="StatementOfStockholdersEquityAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_StatementOfStockholdersEquityAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_StatementOfStockholdersEquityAbstract_lbl" xml:lang="en-US" id="us-gaap_StatementOfStockholdersEquityAbstract_lbl">CONSOLIDATED STATEMENTS OF STOCKHOLDERS' EQUITY [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StatementOfStockholdersEquityAbstract" xlink:to="us-gaap_StatementOfStockholdersEquityAbstract_lbl" xlink:title="label: StatementOfStockholdersEquityAbstract to us-gaap_StatementOfStockholdersEquityAbstract_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensationGross" xlink:label="StockIssuedDuringPeriodSharesShareBasedCompensationGross" xlink:title="StockIssuedDuringPeriodSharesShareBasedCompensationGross" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensationGross_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensationGross_lbl1" xml:lang="en-US" id="us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensationGross_lbl1">Shares Issued, Shares, Share-based Payment Arrangement, before Forfeiture</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StockIssuedDuringPeriodSharesShareBasedCompensationGross" xlink:to="us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensationGross_lbl1" xlink:title="label: StockIssuedDuringPeriodSharesShareBasedCompensationGross to us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensationGross_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.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>
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    <link:label xlink:type="resource" xlink:label="us-gaap_StockIssuedDuringPeriodSharesStockOptionsExercised_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_StockIssuedDuringPeriodSharesStockOptionsExercised_lbl1" xml:lang="en-US" id="us-gaap_StockIssuedDuringPeriodSharesStockOptionsExercised_lbl1">Share-based Compensation Arrangement by Share-based Payment Award, Options, Exercises in Period</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StockIssuedDuringPeriodSharesStockOptionsExercised" xlink:to="us-gaap_StockIssuedDuringPeriodSharesStockOptionsExercised_lbl1" xlink:title="label: StockIssuedDuringPeriodSharesStockOptionsExercised to us-gaap_StockIssuedDuringPeriodSharesStockOptionsExercised_lbl1" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_StockRepurchaseProgramAuthorizedAmount1_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_StockRepurchaseProgramAuthorizedAmount1_lbl" xml:lang="en-US" id="us-gaap_StockRepurchaseProgramAuthorizedAmount1_lbl">Authorized amount of share repurchase program</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StockRepurchaseProgramAuthorizedAmount1" xlink:to="us-gaap_StockRepurchaseProgramAuthorizedAmount1_lbl" xlink:title="label: StockRepurchaseProgramAuthorizedAmount1 to us-gaap_StockRepurchaseProgramAuthorizedAmount1_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_StockRepurchaseProgramAuthorizedAmount1_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_StockRepurchaseProgramAuthorizedAmount1_lbl1" xml:lang="en-US" id="us-gaap_StockRepurchaseProgramAuthorizedAmount1_lbl1">Stock Repurchase Program, Authorized Amount</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StockRepurchaseProgramAuthorizedAmount1" xlink:to="us-gaap_StockRepurchaseProgramAuthorizedAmount1_lbl1" xlink:title="label: StockRepurchaseProgramAuthorizedAmount1 to us-gaap_StockRepurchaseProgramAuthorizedAmount1_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_StockIssuedDuringPeriodValueShareBasedCompensationGross" xlink:label="StockIssuedDuringPeriodValueShareBasedCompensationGross" xlink:title="StockIssuedDuringPeriodValueShareBasedCompensationGross" />
    <link:label xlink:type="resource" xlink:label="us-gaap_StockIssuedDuringPeriodValueShareBasedCompensationGross_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_StockIssuedDuringPeriodValueShareBasedCompensationGross_lbl" xml:lang="en-US" id="us-gaap_StockIssuedDuringPeriodValueShareBasedCompensationGross_lbl">Issuance of common stock in connection with employee stock plans</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StockIssuedDuringPeriodValueShareBasedCompensationGross" xlink:to="us-gaap_StockIssuedDuringPeriodValueShareBasedCompensationGross_lbl" xlink:title="label: StockIssuedDuringPeriodValueShareBasedCompensationGross to us-gaap_StockIssuedDuringPeriodValueShareBasedCompensationGross_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_StockIssuedDuringPeriodValueShareBasedCompensationGross_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_StockIssuedDuringPeriodValueShareBasedCompensationGross_lbl1" xml:lang="en-US" id="us-gaap_StockIssuedDuringPeriodValueShareBasedCompensationGross_lbl1">Shares Issued, Value, Share-based Payment Arrangement, before Forfeiture</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StockIssuedDuringPeriodValueShareBasedCompensationGross" xlink:to="us-gaap_StockIssuedDuringPeriodValueShareBasedCompensationGross_lbl1" xlink:title="label: StockIssuedDuringPeriodValueShareBasedCompensationGross to us-gaap_StockIssuedDuringPeriodValueShareBasedCompensationGross_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.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="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.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/label" xlink:title="us-gaap_StockIssuedDuringPeriodSharesNewIssues_lbl" xml:lang="en-US" id="us-gaap_StockIssuedDuringPeriodSharesNewIssues_lbl">Biogen Stock purchase (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/terseLabel" xlink:title="us-gaap_StockIssuedDuringPeriodSharesNewIssues_lbl1" xml:lang="en-US" id="us-gaap_StockIssuedDuringPeriodSharesNewIssues_lbl1">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_lbl1" xlink:title="label: StockIssuedDuringPeriodSharesNewIssues to us-gaap_StockIssuedDuringPeriodSharesNewIssues_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.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="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_StockRepurchasedAndRetiredDuringPeriodValue" xlink:label="StockRepurchasedAndRetiredDuringPeriodValue" xlink:title="StockRepurchasedAndRetiredDuringPeriodValue" />
    <link:label xlink:type="resource" xlink:label="us-gaap_StockRepurchasedAndRetiredDuringPeriodValue_lbl" xlink:role="http://www.xbrl.org/2009/role/negatedLabel" xlink:title="us-gaap_StockRepurchasedAndRetiredDuringPeriodValue_lbl" xml:lang="en-US" id="us-gaap_StockRepurchasedAndRetiredDuringPeriodValue_lbl">Repurchases and retirements of common stock</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_StockRepurchasedAndRetiredDuringPeriodValue_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_StockRepurchasedAndRetiredDuringPeriodValue_lbl1" xml:lang="en-US" id="us-gaap_StockRepurchasedAndRetiredDuringPeriodValue_lbl1">Stock Repurchased and Retired During Period, Value</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StockRepurchasedAndRetiredDuringPeriodValue" xlink:to="us-gaap_StockRepurchasedAndRetiredDuringPeriodValue_lbl1" xlink:title="label: StockRepurchasedAndRetiredDuringPeriodValue to us-gaap_StockRepurchasedAndRetiredDuringPeriodValue_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_StockIssuedDuringPeriodValueNewIssues" xlink:label="StockIssuedDuringPeriodValueNewIssues" xlink:title="StockIssuedDuringPeriodValueNewIssues" />
    <link:label xlink:type="resource" xlink:label="us-gaap_StockIssuedDuringPeriodValueNewIssues_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_StockIssuedDuringPeriodValueNewIssues_lbl" xml:lang="en-US" id="us-gaap_StockIssuedDuringPeriodValueNewIssues_lbl">Biogen stock purchase</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StockIssuedDuringPeriodValueNewIssues" xlink:to="us-gaap_StockIssuedDuringPeriodValueNewIssues_lbl" xlink:title="label: StockIssuedDuringPeriodValueNewIssues to us-gaap_StockIssuedDuringPeriodValueNewIssues_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_StockIssuedDuringPeriodValueNewIssues_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_StockIssuedDuringPeriodValueNewIssues_lbl1" xml:lang="en-US" id="us-gaap_StockIssuedDuringPeriodValueNewIssues_lbl1">Stock Issued During Period, Value, New Issues</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StockIssuedDuringPeriodValueNewIssues" xlink:to="us-gaap_StockIssuedDuringPeriodValueNewIssues_lbl1" xlink:title="label: StockIssuedDuringPeriodValueNewIssues to us-gaap_StockIssuedDuringPeriodValueNewIssues_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_StockRepurchasedAndRetiredDuringPeriodShares" xlink:label="StockRepurchasedAndRetiredDuringPeriodShares" xlink:title="StockRepurchasedAndRetiredDuringPeriodShares" />
    <link:label xlink:type="resource" xlink:label="us-gaap_StockRepurchasedAndRetiredDuringPeriodShares_lbl" xlink:role="http://www.xbrl.org/2009/role/negatedLabel" xlink:title="us-gaap_StockRepurchasedAndRetiredDuringPeriodShares_lbl" xml:lang="en-US" id="us-gaap_StockRepurchasedAndRetiredDuringPeriodShares_lbl">Repurchases and retirements of common stock (in shares)</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StockRepurchasedAndRetiredDuringPeriodShares" xlink:to="us-gaap_StockRepurchasedAndRetiredDuringPeriodShares_lbl" xlink:title="label: StockRepurchasedAndRetiredDuringPeriodShares to us-gaap_StockRepurchasedAndRetiredDuringPeriodShares_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_StockRepurchasedAndRetiredDuringPeriodShares_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_StockRepurchasedAndRetiredDuringPeriodShares_lbl1" xml:lang="en-US" id="us-gaap_StockRepurchasedAndRetiredDuringPeriodShares_lbl1">Stock Repurchased and Retired During Period, Shares</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StockRepurchasedAndRetiredDuringPeriodShares" xlink:to="us-gaap_StockRepurchasedAndRetiredDuringPeriodShares_lbl1" xlink:title="label: StockRepurchasedAndRetiredDuringPeriodShares to us-gaap_StockRepurchasedAndRetiredDuringPeriodShares_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_StockOptionMember" xlink:label="StockOptionMember" xlink:title="StockOptionMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_StockOptionMember_lbl" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="us-gaap_StockOptionMember_lbl" xml:lang="en-US" id="us-gaap_StockOptionMember_lbl">Stock Options [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StockOptionMember" xlink:to="us-gaap_StockOptionMember_lbl" xlink:title="label: StockOptionMember to us-gaap_StockOptionMember_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_StockOptionMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_StockOptionMember_lbl1" xml:lang="en-US" id="us-gaap_StockOptionMember_lbl1">Equity Option [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StockOptionMember" xlink:to="us-gaap_StockOptionMember_lbl1" xlink:title="label: StockOptionMember to us-gaap_StockOptionMember_lbl1" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_StockRepurchasedDuringPeriodShares_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_StockRepurchasedDuringPeriodShares_lbl" xml:lang="en-US" id="us-gaap_StockRepurchasedDuringPeriodShares_lbl">Shares repurchased (in shares)</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StockRepurchasedDuringPeriodShares" xlink:to="us-gaap_StockRepurchasedDuringPeriodShares_lbl" xlink:title="label: StockRepurchasedDuringPeriodShares to us-gaap_StockRepurchasedDuringPeriodShares_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_StockRepurchasedDuringPeriodShares_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_StockRepurchasedDuringPeriodShares_lbl1" xml:lang="en-US" id="us-gaap_StockRepurchasedDuringPeriodShares_lbl1">Stock Repurchased During Period, Shares</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StockRepurchasedDuringPeriodShares" xlink:to="us-gaap_StockRepurchasedDuringPeriodShares_lbl1" xlink:title="label: StockRepurchasedDuringPeriodShares to us-gaap_StockRepurchasedDuringPeriodShares_lbl1" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_StockholdersEquityNoteDisclosureTextBlock_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_StockholdersEquityNoteDisclosureTextBlock_lbl" xml:lang="en-US" id="us-gaap_StockholdersEquityNoteDisclosureTextBlock_lbl">Stockholders' Equity</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StockholdersEquityNoteDisclosureTextBlock" xlink:to="us-gaap_StockholdersEquityNoteDisclosureTextBlock_lbl" xlink:title="label: StockholdersEquityNoteDisclosureTextBlock to us-gaap_StockholdersEquityNoteDisclosureTextBlock_lbl" />
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StockholdersEquityNoteDisclosureTextBlock" xlink:to="us-gaap_StockholdersEquityNoteDisclosureTextBlock_lbl1" xlink:title="label: StockholdersEquityNoteDisclosureTextBlock to us-gaap_StockholdersEquityNoteDisclosureTextBlock_lbl1" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_StockholdersEquityPolicyTextBlock_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_StockholdersEquityPolicyTextBlock_lbl" xml:lang="en-US" id="us-gaap_StockholdersEquityPolicyTextBlock_lbl">Accumulated Other Comprehensive Loss</link:label>
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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_lbl1" xlink:title="label: WeightedAverageNumberOfSharesOutstandingBasic to us-gaap_WeightedAverageNumberOfSharesOutstandingBasic_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding" xlink:label="WeightedAverageNumberOfDilutedSharesOutstanding" xlink:title="WeightedAverageNumberOfDilutedSharesOutstanding" />
    <link:label xlink:type="resource" xlink:label="us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding_lbl" xml:lang="en-US" id="us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding_lbl">Shares used in computing diluted net income (loss) per share (in shares)</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="WeightedAverageNumberOfDilutedSharesOutstanding" xlink:to="us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding_lbl" xlink:title="label: WeightedAverageNumberOfDilutedSharesOutstanding to us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding_lbl1" xlink:role="http://www.xbrl.org/2003/role/totalLabel" xlink:title="us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding_lbl1" xml:lang="en-US" id="us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding_lbl1">Shares used in computing diluted net income per share (in shares)</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="WeightedAverageNumberOfDilutedSharesOutstanding" xlink:to="us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding_lbl1" xlink:title="label: WeightedAverageNumberOfDilutedSharesOutstanding to us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding_lbl1" />
    <link:label xlink:type="resource" xlink:label="us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding_lbl2" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding_lbl2" xml:lang="en-US" id="us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding_lbl2">Weighted Average Number of Shares Outstanding, Diluted</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="WeightedAverageNumberOfDilutedSharesOutstanding" xlink:to="us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding_lbl2" xlink:title="label: WeightedAverageNumberOfDilutedSharesOutstanding to us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding_lbl2" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_WeightedAverageNumberDilutedSharesOutstandingAdjustmentAbstract" xlink:label="WeightedAverageNumberDilutedSharesOutstandingAdjustmentAbstract" xlink:title="WeightedAverageNumberDilutedSharesOutstandingAdjustmentAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_WeightedAverageNumberDilutedSharesOutstandingAdjustmentAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_WeightedAverageNumberDilutedSharesOutstandingAdjustmentAbstract_lbl" xml:lang="en-US" id="us-gaap_WeightedAverageNumberDilutedSharesOutstandingAdjustmentAbstract_lbl">Effect of Diluted Securities [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="WeightedAverageNumberDilutedSharesOutstandingAdjustmentAbstract" xlink:to="us-gaap_WeightedAverageNumberDilutedSharesOutstandingAdjustmentAbstract_lbl" xlink:title="label: WeightedAverageNumberDilutedSharesOutstandingAdjustmentAbstract to us-gaap_WeightedAverageNumberDilutedSharesOutstandingAdjustmentAbstract_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_WeightedAverageNumberOfSharesOutstandingDilutedDisclosureItemsAbstract" xlink:label="WeightedAverageNumberOfSharesOutstandingDilutedDisclosureItemsAbstract" xlink:title="WeightedAverageNumberOfSharesOutstandingDilutedDisclosureItemsAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_WeightedAverageNumberOfSharesOutstandingDilutedDisclosureItemsAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_WeightedAverageNumberOfSharesOutstandingDilutedDisclosureItemsAbstract_lbl" xml:lang="en-US" id="us-gaap_WeightedAverageNumberOfSharesOutstandingDilutedDisclosureItemsAbstract_lbl">Shares (Denominator) [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="WeightedAverageNumberOfSharesOutstandingDilutedDisclosureItemsAbstract" xlink:to="us-gaap_WeightedAverageNumberOfSharesOutstandingDilutedDisclosureItemsAbstract_lbl" xlink:title="label: WeightedAverageNumberOfSharesOutstandingDilutedDisclosureItemsAbstract to us-gaap_WeightedAverageNumberOfSharesOutstandingDilutedDisclosureItemsAbstract_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_WeightedAverageNumberOfSharesOutstandingDilutedDisclosureItemsAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_WeightedAverageNumberOfSharesOutstandingDilutedDisclosureItemsAbstract_lbl1" xml:lang="en-US" id="us-gaap_WeightedAverageNumberOfSharesOutstandingDilutedDisclosureItemsAbstract_lbl1">Weighted Average Number of Shares Outstanding Reconciliation [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="WeightedAverageNumberOfSharesOutstandingDilutedDisclosureItemsAbstract" xlink:to="us-gaap_WeightedAverageNumberOfSharesOutstandingDilutedDisclosureItemsAbstract_lbl1" xlink:title="label: WeightedAverageNumberOfSharesOutstandingDilutedDisclosureItemsAbstract to us-gaap_WeightedAverageNumberOfSharesOutstandingDilutedDisclosureItemsAbstract_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.xsd#srt_ConsolidatedEntitiesDomain" xlink:label="ConsolidatedEntitiesDomain" xlink:title="ConsolidatedEntitiesDomain" />
    <link:label xlink:type="resource" xlink:label="srt_ConsolidatedEntitiesDomain_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="srt_ConsolidatedEntitiesDomain_lbl" xml:lang="en-US" id="srt_ConsolidatedEntitiesDomain_lbl">Consolidated Entities [Domain]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConsolidatedEntitiesDomain" xlink:to="srt_ConsolidatedEntitiesDomain_lbl" xlink:title="label: ConsolidatedEntitiesDomain to srt_ConsolidatedEntitiesDomain_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.xsd#srt_ConsolidatedEntitiesAxis" xlink:label="ConsolidatedEntitiesAxis" xlink:title="ConsolidatedEntitiesAxis" />
    <link:label xlink:type="resource" xlink:label="srt_ConsolidatedEntitiesAxis_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="srt_ConsolidatedEntitiesAxis_lbl" xml:lang="en-US" id="srt_ConsolidatedEntitiesAxis_lbl">Consolidated Entities [Axis]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConsolidatedEntitiesAxis" xlink:to="srt_ConsolidatedEntitiesAxis_lbl" xlink:title="label: ConsolidatedEntitiesAxis to srt_ConsolidatedEntitiesAxis_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.xsd#srt_ConsolidationItemsAxis" xlink:label="ConsolidationItemsAxis" xlink:title="ConsolidationItemsAxis" />
    <link:label xlink:type="resource" xlink:label="srt_ConsolidationItemsAxis_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="srt_ConsolidationItemsAxis_lbl" xml:lang="en-US" id="srt_ConsolidationItemsAxis_lbl">Consolidation Items [Axis]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConsolidationItemsAxis" xlink:to="srt_ConsolidationItemsAxis_lbl" xlink:title="label: ConsolidationItemsAxis to srt_ConsolidationItemsAxis_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.xsd#srt_ConsolidationItemsDomain" xlink:label="ConsolidationItemsDomain" xlink:title="ConsolidationItemsDomain" />
    <link:label xlink:type="resource" xlink:label="srt_ConsolidationItemsDomain_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="srt_ConsolidationItemsDomain_lbl" xml:lang="en-US" id="srt_ConsolidationItemsDomain_lbl">Consolidation Items [Domain]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConsolidationItemsDomain" xlink:to="srt_ConsolidationItemsDomain_lbl" xlink:title="label: ConsolidationItemsDomain to srt_ConsolidationItemsDomain_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.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">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="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.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="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.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/terseLabel" 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:label xlink:type="resource" xlink:label="srt_MaximumMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="srt_MaximumMember_lbl1" xml:lang="en-US" id="srt_MaximumMember_lbl1">Maximum [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumMember" xlink:to="srt_MaximumMember_lbl1" xlink:title="label: MaximumMember to srt_MaximumMember_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.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/terseLabel" xlink:title="srt_MinimumMember_lbl" xml:lang="en-US" id="srt_MinimumMember_lbl">Minimum [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MinimumMember" xlink:to="srt_MinimumMember_lbl" xlink:title="label: MinimumMember to srt_MinimumMember_lbl" />
    <link:label xlink:type="resource" xlink:label="srt_MinimumMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="srt_MinimumMember_lbl1" xml:lang="en-US" id="srt_MinimumMember_lbl1">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_lbl1" xlink:title="label: MinimumMember to srt_MinimumMember_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.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" />
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    <link:label xlink:type="resource" xlink:label="srt_OwnershipDomain_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="srt_OwnershipDomain_lbl" xml:lang="en-US" id="srt_OwnershipDomain_lbl">Ownership [Domain]</link:label>
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    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.xsd#srt_OwnershipAxis" xlink:label="OwnershipAxis" xlink:title="OwnershipAxis" />
    <link:label xlink:type="resource" xlink:label="srt_OwnershipAxis_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="srt_OwnershipAxis_lbl" xml:lang="en-US" id="srt_OwnershipAxis_lbl">Ownership [Axis]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OwnershipAxis" xlink:to="srt_OwnershipAxis_lbl" xlink:title="label: OwnershipAxis to srt_OwnershipAxis_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.xsd#srt_ProductsAndServicesDomain" xlink:label="ProductsAndServicesDomain" xlink:title="ProductsAndServicesDomain" />
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    <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" />
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    <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" />
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    <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/2019/dei-2019-01-31.xsd#dei_EntityAddressCityOrTown" xlink:label="EntityAddressCityOrTown" xlink:title="EntityAddressCityOrTown" />
    <link:label xlink:type="resource" xlink:label="dei_EntityAddressCityOrTown_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_EntityAddressCityOrTown_lbl" xml:lang="en-US" id="dei_EntityAddressCityOrTown_lbl">Entity Address, City or Town</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EntityAddressCityOrTown" xlink:to="dei_EntityAddressCityOrTown_lbl" xlink:title="label: EntityAddressCityOrTown to dei_EntityAddressCityOrTown_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2019/dei-2019-01-31.xsd#dei_CurrentFiscalYearEndDate" xlink:label="CurrentFiscalYearEndDate" xlink:title="CurrentFiscalYearEndDate" />
    <link:label xlink:type="resource" xlink:label="dei_CurrentFiscalYearEndDate_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_CurrentFiscalYearEndDate_lbl" xml:lang="en-US" id="dei_CurrentFiscalYearEndDate_lbl">Current Fiscal Year End Date</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CurrentFiscalYearEndDate" xlink:to="dei_CurrentFiscalYearEndDate_lbl" xlink:title="label: CurrentFiscalYearEndDate to dei_CurrentFiscalYearEndDate_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2019/dei-2019-01-31.xsd#dei_DocumentPeriodEndDate" xlink:label="DocumentPeriodEndDate" xlink:title="DocumentPeriodEndDate" />
    <link:label xlink:type="resource" xlink:label="dei_DocumentPeriodEndDate_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_DocumentPeriodEndDate_lbl" xml:lang="en-US" id="dei_DocumentPeriodEndDate_lbl">Document Period End Date</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DocumentPeriodEndDate" xlink:to="dei_DocumentPeriodEndDate_lbl" xlink:title="label: DocumentPeriodEndDate to dei_DocumentPeriodEndDate_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2019/dei-2019-01-31.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>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EntityIncorporationStateCountryCode" xlink:to="dei_EntityIncorporationStateCountryCode_lbl" xlink:title="label: EntityIncorporationStateCountryCode to dei_EntityIncorporationStateCountryCode_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2019/dei-2019-01-31.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/2019/dei-2019-01-31.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/2019/dei-2019-01-31.xsd#dei_EntityAddressStateOrProvince" xlink:label="EntityAddressStateOrProvince" xlink:title="EntityAddressStateOrProvince" />
    <link:label xlink:type="resource" xlink:label="dei_EntityAddressStateOrProvince_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_EntityAddressStateOrProvince_lbl" xml:lang="en-US" id="dei_EntityAddressStateOrProvince_lbl">Entity Address, State or Province</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EntityAddressStateOrProvince" xlink:to="dei_EntityAddressStateOrProvince_lbl" xlink:title="label: EntityAddressStateOrProvince to dei_EntityAddressStateOrProvince_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2019/dei-2019-01-31.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/2019/dei-2019-01-31.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/2019/dei-2019-01-31.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/2019/dei-2019-01-31.xsd#dei_EntityWellKnownSeasonedIssuer" xlink:label="EntityWellKnownSeasonedIssuer" xlink:title="EntityWellKnownSeasonedIssuer" />
    <link:label xlink:type="resource" xlink:label="dei_EntityWellKnownSeasonedIssuer_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_EntityWellKnownSeasonedIssuer_lbl" xml:lang="en-US" id="dei_EntityWellKnownSeasonedIssuer_lbl">Entity Well-known Seasoned Issuer</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EntityWellKnownSeasonedIssuer" xlink:to="dei_EntityWellKnownSeasonedIssuer_lbl" xlink:title="label: EntityWellKnownSeasonedIssuer to dei_EntityWellKnownSeasonedIssuer_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2019/dei-2019-01-31.xsd#dei_EntityVoluntaryFilers" xlink:label="EntityVoluntaryFilers" xlink:title="EntityVoluntaryFilers" />
    <link:label xlink:type="resource" xlink:label="dei_EntityVoluntaryFilers_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_EntityVoluntaryFilers_lbl" xml:lang="en-US" id="dei_EntityVoluntaryFilers_lbl">Entity Voluntary Filers</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EntityVoluntaryFilers" xlink:to="dei_EntityVoluntaryFilers_lbl" xlink:title="label: EntityVoluntaryFilers to dei_EntityVoluntaryFilers_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2019/dei-2019-01-31.xsd#dei_EntityCurrentReportingStatus" xlink:label="EntityCurrentReportingStatus" xlink:title="EntityCurrentReportingStatus" />
    <link:label xlink:type="resource" xlink:label="dei_EntityCurrentReportingStatus_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_EntityCurrentReportingStatus_lbl" xml:lang="en-US" id="dei_EntityCurrentReportingStatus_lbl">Entity Current Reporting Status</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EntityCurrentReportingStatus" xlink:to="dei_EntityCurrentReportingStatus_lbl" xlink:title="label: EntityCurrentReportingStatus to dei_EntityCurrentReportingStatus_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2019/dei-2019-01-31.xsd#dei_EntityFilerCategory" xlink:label="EntityFilerCategory" xlink:title="EntityFilerCategory" />
    <link:label xlink:type="resource" xlink:label="dei_EntityFilerCategory_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_EntityFilerCategory_lbl" xml:lang="en-US" id="dei_EntityFilerCategory_lbl">Entity Filer Category</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EntityFilerCategory" xlink:to="dei_EntityFilerCategory_lbl" xlink:title="label: EntityFilerCategory to dei_EntityFilerCategory_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2019/dei-2019-01-31.xsd#dei_EntityPublicFloat" xlink:label="EntityPublicFloat" xlink:title="EntityPublicFloat" />
    <link:label xlink:type="resource" xlink:label="dei_EntityPublicFloat_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_EntityPublicFloat_lbl" xml:lang="en-US" id="dei_EntityPublicFloat_lbl">Entity Public Float</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EntityPublicFloat" xlink:to="dei_EntityPublicFloat_lbl" xlink:title="label: EntityPublicFloat to dei_EntityPublicFloat_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2019/dei-2019-01-31.xsd#dei_EntityRegistrantName" xlink:label="EntityRegistrantName" xlink:title="EntityRegistrantName" />
    <link:label xlink:type="resource" xlink:label="dei_EntityRegistrantName_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_EntityRegistrantName_lbl" xml:lang="en-US" id="dei_EntityRegistrantName_lbl">Entity Registrant Name</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EntityRegistrantName" xlink:to="dei_EntityRegistrantName_lbl" xlink:title="label: EntityRegistrantName to dei_EntityRegistrantName_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2019/dei-2019-01-31.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>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EntityCentralIndexKey" xlink:to="dei_EntityCentralIndexKey_lbl" xlink:title="label: EntityCentralIndexKey to dei_EntityCentralIndexKey_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2019/dei-2019-01-31.xsd#dei_EntityTaxIdentificationNumber" xlink:label="EntityTaxIdentificationNumber" xlink:title="EntityTaxIdentificationNumber" />
    <link:label xlink:type="resource" xlink:label="dei_EntityTaxIdentificationNumber_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_EntityTaxIdentificationNumber_lbl" xml:lang="en-US" id="dei_EntityTaxIdentificationNumber_lbl">Entity Tax Identification Number</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EntityTaxIdentificationNumber" xlink:to="dei_EntityTaxIdentificationNumber_lbl" xlink:title="label: EntityTaxIdentificationNumber to dei_EntityTaxIdentificationNumber_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2019/dei-2019-01-31.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/2019/dei-2019-01-31.xsd#dei_DocumentFiscalYearFocus" xlink:label="DocumentFiscalYearFocus" xlink:title="DocumentFiscalYearFocus" />
    <link:label xlink:type="resource" xlink:label="dei_DocumentFiscalYearFocus_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_DocumentFiscalYearFocus_lbl" xml:lang="en-US" id="dei_DocumentFiscalYearFocus_lbl">Document Fiscal Year Focus</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DocumentFiscalYearFocus" xlink:to="dei_DocumentFiscalYearFocus_lbl" xlink:title="label: DocumentFiscalYearFocus to dei_DocumentFiscalYearFocus_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2019/dei-2019-01-31.xsd#dei_DocumentFiscalPeriodFocus" xlink:label="DocumentFiscalPeriodFocus" xlink:title="DocumentFiscalPeriodFocus" />
    <link:label xlink:type="resource" xlink:label="dei_DocumentFiscalPeriodFocus_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_DocumentFiscalPeriodFocus_lbl" xml:lang="en-US" id="dei_DocumentFiscalPeriodFocus_lbl">Document Fiscal Period Focus</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DocumentFiscalPeriodFocus" xlink:to="dei_DocumentFiscalPeriodFocus_lbl" xlink:title="label: DocumentFiscalPeriodFocus to dei_DocumentFiscalPeriodFocus_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2019/dei-2019-01-31.xsd#dei_DocumentType" xlink:label="DocumentType" xlink:title="DocumentType" />
    <link:label xlink:type="resource" xlink:label="dei_DocumentType_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_DocumentType_lbl" xml:lang="en-US" id="dei_DocumentType_lbl">Document Type</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DocumentType" xlink:to="dei_DocumentType_lbl" xlink:title="label: DocumentType to dei_DocumentType_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2019/dei-2019-01-31.xsd#dei_DocumentAnnualReport" xlink:label="DocumentAnnualReport" xlink:title="DocumentAnnualReport" />
    <link:label xlink:type="resource" xlink:label="dei_DocumentAnnualReport_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_DocumentAnnualReport_lbl" xml:lang="en-US" id="dei_DocumentAnnualReport_lbl">Document Annual Report</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DocumentAnnualReport" xlink:to="dei_DocumentAnnualReport_lbl" xlink:title="label: DocumentAnnualReport to dei_DocumentAnnualReport_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2019/dei-2019-01-31.xsd#dei_DocumentTransitionReport" xlink:label="DocumentTransitionReport" xlink:title="DocumentTransitionReport" />
    <link:label xlink:type="resource" xlink:label="dei_DocumentTransitionReport_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_DocumentTransitionReport_lbl" xml:lang="en-US" id="dei_DocumentTransitionReport_lbl">Document Transition Report</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DocumentTransitionReport" xlink:to="dei_DocumentTransitionReport_lbl" xlink:title="label: DocumentTransitionReport to dei_DocumentTransitionReport_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2019/dei-2019-01-31.xsd#dei_EntityInteractiveDataCurrent" xlink:label="EntityInteractiveDataCurrent" xlink:title="EntityInteractiveDataCurrent" />
    <link:label xlink:type="resource" xlink:label="dei_EntityInteractiveDataCurrent_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_EntityInteractiveDataCurrent_lbl" xml:lang="en-US" id="dei_EntityInteractiveDataCurrent_lbl">Entity Interactive Data Current</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EntityInteractiveDataCurrent" xlink:to="dei_EntityInteractiveDataCurrent_lbl" xlink:title="label: EntityInteractiveDataCurrent to dei_EntityInteractiveDataCurrent_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2019/dei-2019-01-31.xsd#dei_EntityFileNumber" xlink:label="EntityFileNumber" xlink:title="EntityFileNumber" />
    <link:label xlink:type="resource" xlink:label="dei_EntityFileNumber_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_EntityFileNumber_lbl" xml:lang="en-US" id="dei_EntityFileNumber_lbl">Entity File Number</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EntityFileNumber" xlink:to="dei_EntityFileNumber_lbl" xlink:title="label: EntityFileNumber to dei_EntityFileNumber_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2019/dei-2019-01-31.xsd#dei_EntityShellCompany" xlink:label="EntityShellCompany" xlink:title="EntityShellCompany" />
    <link:label xlink:type="resource" xlink:label="dei_EntityShellCompany_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_EntityShellCompany_lbl" xml:lang="en-US" id="dei_EntityShellCompany_lbl">Entity Shell Company</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EntityShellCompany" xlink:to="dei_EntityShellCompany_lbl" xlink:title="label: EntityShellCompany to dei_EntityShellCompany_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2019/dei-2019-01-31.xsd#dei_EntityEmergingGrowthCompany" xlink:label="EntityEmergingGrowthCompany" xlink:title="EntityEmergingGrowthCompany" />
    <link:label xlink:type="resource" xlink:label="dei_EntityEmergingGrowthCompany_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_EntityEmergingGrowthCompany_lbl" xml:lang="en-US" id="dei_EntityEmergingGrowthCompany_lbl">Entity Emerging Growth Company</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EntityEmergingGrowthCompany" xlink:to="dei_EntityEmergingGrowthCompany_lbl" xlink:title="label: EntityEmergingGrowthCompany to dei_EntityEmergingGrowthCompany_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2019/dei-2019-01-31.xsd#dei_EntitySmallBusiness" xlink:label="EntitySmallBusiness" xlink:title="EntitySmallBusiness" />
    <link:label xlink:type="resource" xlink:label="dei_EntitySmallBusiness_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_EntitySmallBusiness_lbl" xml:lang="en-US" id="dei_EntitySmallBusiness_lbl">Entity Small Business</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EntitySmallBusiness" xlink:to="dei_EntitySmallBusiness_lbl" xlink:title="label: EntitySmallBusiness to dei_EntitySmallBusiness_lbl" />
    <link:loc xlink:type="locator" xlink:href="ions-20201231.xsd#ions_UpdatedEuropeanDistributionModelEmployeeSeveranceAndRetentionMember" xlink:label="UpdatedEuropeanDistributionModelEmployeeSeveranceAndRetentionMember" xlink:title="UpdatedEuropeanDistributionModelEmployeeSeveranceAndRetentionMember" />
    <link:label xlink:type="resource" xlink:label="ions_UpdatedEuropeanDistributionModelEmployeeSeveranceAndRetentionMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_UpdatedEuropeanDistributionModelEmployeeSeveranceAndRetentionMember_lbl" xml:lang="en-US" id="ions_UpdatedEuropeanDistributionModelEmployeeSeveranceAndRetentionMember_lbl">Termination of employees and retention of key employees for a specific period of time associated with an updated European Distribution model for TEGSEDI and WAYLIVRA.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="UpdatedEuropeanDistributionModelEmployeeSeveranceAndRetentionMember" xlink:to="ions_UpdatedEuropeanDistributionModelEmployeeSeveranceAndRetentionMember_lbl" xlink:title="label: UpdatedEuropeanDistributionModelEmployeeSeveranceAndRetentionMember to ions_UpdatedEuropeanDistributionModelEmployeeSeveranceAndRetentionMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_UpdatedEuropeanDistributionModelEmployeeSeveranceAndRetentionMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_UpdatedEuropeanDistributionModelEmployeeSeveranceAndRetentionMember_lbl1" xml:lang="en-US" id="ions_UpdatedEuropeanDistributionModelEmployeeSeveranceAndRetentionMember_lbl1">Updated European Distribution Model, Employee Severance and Retention [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="UpdatedEuropeanDistributionModelEmployeeSeveranceAndRetentionMember" xlink:to="ions_UpdatedEuropeanDistributionModelEmployeeSeveranceAndRetentionMember_lbl1" xlink:title="label: UpdatedEuropeanDistributionModelEmployeeSeveranceAndRetentionMember to ions_UpdatedEuropeanDistributionModelEmployeeSeveranceAndRetentionMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_UpdatedEuropeanDistributionModelEmployeeSeveranceAndRetentionMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_UpdatedEuropeanDistributionModelEmployeeSeveranceAndRetentionMember_lbl2" xml:lang="en-US" id="ions_UpdatedEuropeanDistributionModelEmployeeSeveranceAndRetentionMember_lbl2">Severance and Retention Related to Updated European Distribution Model [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="UpdatedEuropeanDistributionModelEmployeeSeveranceAndRetentionMember" xlink:to="ions_UpdatedEuropeanDistributionModelEmployeeSeveranceAndRetentionMember_lbl2" xlink:title="label: UpdatedEuropeanDistributionModelEmployeeSeveranceAndRetentionMember to ions_UpdatedEuropeanDistributionModelEmployeeSeveranceAndRetentionMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20201231.xsd#ions_ConsolidationLessThanWhollyOwnedSubsidiaryParentOwnershipInterestChangesPurchaseOfInterestByParentPricePerShare" xlink:label="ConsolidationLessThanWhollyOwnedSubsidiaryParentOwnershipInterestChangesPurchaseOfInterestByParentPricePerShare" xlink:title="ConsolidationLessThanWhollyOwnedSubsidiaryParentOwnershipInterestChangesPurchaseOfInterestByParentPricePerShare" />
    <link:label xlink:type="resource" xlink:label="ions_ConsolidationLessThanWhollyOwnedSubsidiaryParentOwnershipInterestChangesPurchaseOfInterestByParentPricePerShare_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_ConsolidationLessThanWhollyOwnedSubsidiaryParentOwnershipInterestChangesPurchaseOfInterestByParentPricePerShare_lbl" xml:lang="en-US" id="ions_ConsolidationLessThanWhollyOwnedSubsidiaryParentOwnershipInterestChangesPurchaseOfInterestByParentPricePerShare_lbl">Per share amount paid for the shares of the subsidiary purchased by the parent during the period, thereby effecting a change in total (consolidated) equity attributable to the parent.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConsolidationLessThanWhollyOwnedSubsidiaryParentOwnershipInterestChangesPurchaseOfInterestByParentPricePerShare" xlink:to="ions_ConsolidationLessThanWhollyOwnedSubsidiaryParentOwnershipInterestChangesPurchaseOfInterestByParentPricePerShare_lbl" xlink:title="label: ConsolidationLessThanWhollyOwnedSubsidiaryParentOwnershipInterestChangesPurchaseOfInterestByParentPricePerShare to ions_ConsolidationLessThanWhollyOwnedSubsidiaryParentOwnershipInterestChangesPurchaseOfInterestByParentPricePerShare_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_ConsolidationLessThanWhollyOwnedSubsidiaryParentOwnershipInterestChangesPurchaseOfInterestByParentPricePerShare_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_ConsolidationLessThanWhollyOwnedSubsidiaryParentOwnershipInterestChangesPurchaseOfInterestByParentPricePerShare_lbl1" xml:lang="en-US" id="ions_ConsolidationLessThanWhollyOwnedSubsidiaryParentOwnershipInterestChangesPurchaseOfInterestByParentPricePerShare_lbl1">Consolidation, Less than Wholly Owned Subsidiary, Parent Ownership Interest, Changes, Purchase of Interest by Parent, Price per Share</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConsolidationLessThanWhollyOwnedSubsidiaryParentOwnershipInterestChangesPurchaseOfInterestByParentPricePerShare" xlink:to="ions_ConsolidationLessThanWhollyOwnedSubsidiaryParentOwnershipInterestChangesPurchaseOfInterestByParentPricePerShare_lbl1" xlink:title="label: ConsolidationLessThanWhollyOwnedSubsidiaryParentOwnershipInterestChangesPurchaseOfInterestByParentPricePerShare to ions_ConsolidationLessThanWhollyOwnedSubsidiaryParentOwnershipInterestChangesPurchaseOfInterestByParentPricePerShare_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_ConsolidationLessThanWhollyOwnedSubsidiaryParentOwnershipInterestChangesPurchaseOfInterestByParentPricePerShare_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_ConsolidationLessThanWhollyOwnedSubsidiaryParentOwnershipInterestChangesPurchaseOfInterestByParentPricePerShare_lbl2" xml:lang="en-US" id="ions_ConsolidationLessThanWhollyOwnedSubsidiaryParentOwnershipInterestChangesPurchaseOfInterestByParentPricePerShare_lbl2">Purchase 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="ConsolidationLessThanWhollyOwnedSubsidiaryParentOwnershipInterestChangesPurchaseOfInterestByParentPricePerShare" xlink:to="ions_ConsolidationLessThanWhollyOwnedSubsidiaryParentOwnershipInterestChangesPurchaseOfInterestByParentPricePerShare_lbl2" xlink:title="label: ConsolidationLessThanWhollyOwnedSubsidiaryParentOwnershipInterestChangesPurchaseOfInterestByParentPricePerShare to ions_ConsolidationLessThanWhollyOwnedSubsidiaryParentOwnershipInterestChangesPurchaseOfInterestByParentPricePerShare_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20201231.xsd#ions_CashPurchasePriceOfEquityAwards" xlink:label="CashPurchasePriceOfEquityAwards" xlink:title="CashPurchasePriceOfEquityAwards" />
    <link:label xlink:type="resource" xlink:label="ions_CashPurchasePriceOfEquityAwards_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_CashPurchasePriceOfEquityAwards_lbl" xml:lang="en-US" id="ions_CashPurchasePriceOfEquityAwards_lbl">Cash purchase price for each equity award held, including stock options and restricted stock units (RSUs).</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CashPurchasePriceOfEquityAwards" xlink:to="ions_CashPurchasePriceOfEquityAwards_lbl" xlink:title="label: CashPurchasePriceOfEquityAwards to ions_CashPurchasePriceOfEquityAwards_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_CashPurchasePriceOfEquityAwards_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_CashPurchasePriceOfEquityAwards_lbl1" xml:lang="en-US" id="ions_CashPurchasePriceOfEquityAwards_lbl1">Cash purchase price of equity awards</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CashPurchasePriceOfEquityAwards" xlink:to="ions_CashPurchasePriceOfEquityAwards_lbl1" xlink:title="label: CashPurchasePriceOfEquityAwards to ions_CashPurchasePriceOfEquityAwards_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_CashPurchasePriceOfEquityAwards_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_CashPurchasePriceOfEquityAwards_lbl2" xml:lang="en-US" id="ions_CashPurchasePriceOfEquityAwards_lbl2">Cash purchase price of equity awards (in dollars per share)</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CashPurchasePriceOfEquityAwards" xlink:to="ions_CashPurchasePriceOfEquityAwards_lbl2" xlink:title="label: CashPurchasePriceOfEquityAwards to ions_CashPurchasePriceOfEquityAwards_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20201231.xsd#ions_AkceaAcquisitionEmployeeRetentionMember" xlink:label="AkceaAcquisitionEmployeeRetentionMember" xlink:title="AkceaAcquisitionEmployeeRetentionMember" />
    <link:label xlink:type="resource" xlink:label="ions_AkceaAcquisitionEmployeeRetentionMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_AkceaAcquisitionEmployeeRetentionMember_lbl" xml:lang="en-US" id="ions_AkceaAcquisitionEmployeeRetentionMember_lbl">Retention of key employee with continued employment for a specific period of time as part of the Akcea Acquisition.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AkceaAcquisitionEmployeeRetentionMember" xlink:to="ions_AkceaAcquisitionEmployeeRetentionMember_lbl" xlink:title="label: AkceaAcquisitionEmployeeRetentionMember to ions_AkceaAcquisitionEmployeeRetentionMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_AkceaAcquisitionEmployeeRetentionMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_AkceaAcquisitionEmployeeRetentionMember_lbl1" xml:lang="en-US" id="ions_AkceaAcquisitionEmployeeRetentionMember_lbl1">Akcea Acquisition, Employee Retention [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AkceaAcquisitionEmployeeRetentionMember" xlink:to="ions_AkceaAcquisitionEmployeeRetentionMember_lbl1" xlink:title="label: AkceaAcquisitionEmployeeRetentionMember to ions_AkceaAcquisitionEmployeeRetentionMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_AkceaAcquisitionEmployeeRetentionMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_AkceaAcquisitionEmployeeRetentionMember_lbl2" xml:lang="en-US" id="ions_AkceaAcquisitionEmployeeRetentionMember_lbl2">Retention Related to Akcea Acquisition [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AkceaAcquisitionEmployeeRetentionMember" xlink:to="ions_AkceaAcquisitionEmployeeRetentionMember_lbl2" xlink:title="label: AkceaAcquisitionEmployeeRetentionMember to ions_AkceaAcquisitionEmployeeRetentionMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20201231.xsd#ions_AkceaAcquisitionEmployeeSeveranceAndRetentionMember" xlink:label="AkceaAcquisitionEmployeeSeveranceAndRetentionMember" xlink:title="AkceaAcquisitionEmployeeSeveranceAndRetentionMember" />
    <link:label xlink:type="resource" xlink:label="ions_AkceaAcquisitionEmployeeSeveranceAndRetentionMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_AkceaAcquisitionEmployeeSeveranceAndRetentionMember_lbl" xml:lang="en-US" id="ions_AkceaAcquisitionEmployeeSeveranceAndRetentionMember_lbl">Termination of employees and retention of key employees for a specific period of time as part of the Akcea Acquisition.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AkceaAcquisitionEmployeeSeveranceAndRetentionMember" xlink:to="ions_AkceaAcquisitionEmployeeSeveranceAndRetentionMember_lbl" xlink:title="label: AkceaAcquisitionEmployeeSeveranceAndRetentionMember to ions_AkceaAcquisitionEmployeeSeveranceAndRetentionMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_AkceaAcquisitionEmployeeSeveranceAndRetentionMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_AkceaAcquisitionEmployeeSeveranceAndRetentionMember_lbl1" xml:lang="en-US" id="ions_AkceaAcquisitionEmployeeSeveranceAndRetentionMember_lbl1">Akcea Acquisition, Employee Severance and Retention [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AkceaAcquisitionEmployeeSeveranceAndRetentionMember" xlink:to="ions_AkceaAcquisitionEmployeeSeveranceAndRetentionMember_lbl1" xlink:title="label: AkceaAcquisitionEmployeeSeveranceAndRetentionMember to ions_AkceaAcquisitionEmployeeSeveranceAndRetentionMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_AkceaAcquisitionEmployeeSeveranceAndRetentionMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_AkceaAcquisitionEmployeeSeveranceAndRetentionMember_lbl2" xml:lang="en-US" id="ions_AkceaAcquisitionEmployeeSeveranceAndRetentionMember_lbl2">Severance and Retention Related to Akcea Acquisition [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AkceaAcquisitionEmployeeSeveranceAndRetentionMember" xlink:to="ions_AkceaAcquisitionEmployeeSeveranceAndRetentionMember_lbl2" xlink:title="label: AkceaAcquisitionEmployeeSeveranceAndRetentionMember to ions_AkceaAcquisitionEmployeeSeveranceAndRetentionMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20201231.xsd#ions_EmployeeRelatedLiabilitiesCurrentMember" xlink:label="EmployeeRelatedLiabilitiesCurrentMember" xlink:title="EmployeeRelatedLiabilitiesCurrentMember" />
    <link:label xlink:type="resource" xlink:label="ions_EmployeeRelatedLiabilitiesCurrentMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_EmployeeRelatedLiabilitiesCurrentMember_lbl" xml:lang="en-US" id="ions_EmployeeRelatedLiabilitiesCurrentMember_lbl">Primary financial statement caption encompassing current employee-related liabilities.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EmployeeRelatedLiabilitiesCurrentMember" xlink:to="ions_EmployeeRelatedLiabilitiesCurrentMember_lbl" xlink:title="label: EmployeeRelatedLiabilitiesCurrentMember to ions_EmployeeRelatedLiabilitiesCurrentMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_EmployeeRelatedLiabilitiesCurrentMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_EmployeeRelatedLiabilitiesCurrentMember_lbl1" xml:lang="en-US" id="ions_EmployeeRelatedLiabilitiesCurrentMember_lbl1">Employee-related Liabilities, Current [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EmployeeRelatedLiabilitiesCurrentMember" xlink:to="ions_EmployeeRelatedLiabilitiesCurrentMember_lbl1" xlink:title="label: EmployeeRelatedLiabilitiesCurrentMember to ions_EmployeeRelatedLiabilitiesCurrentMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_EmployeeRelatedLiabilitiesCurrentMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_EmployeeRelatedLiabilitiesCurrentMember_lbl2" xml:lang="en-US" id="ions_EmployeeRelatedLiabilitiesCurrentMember_lbl2">Accrued Compensation [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EmployeeRelatedLiabilitiesCurrentMember" xlink:to="ions_EmployeeRelatedLiabilitiesCurrentMember_lbl2" xlink:title="label: EmployeeRelatedLiabilitiesCurrentMember to ions_EmployeeRelatedLiabilitiesCurrentMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20201231.xsd#ions_ResearchAndDevelopmentExpensesMember" xlink:label="ResearchAndDevelopmentExpensesMember" xlink:title="ResearchAndDevelopmentExpensesMember" />
    <link:label xlink:type="resource" xlink:label="ions_ResearchAndDevelopmentExpensesMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_ResearchAndDevelopmentExpensesMember_lbl" xml:lang="en-US" id="ions_ResearchAndDevelopmentExpensesMember_lbl">Primary financial statement caption encompassing research and development expense.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ResearchAndDevelopmentExpensesMember" xlink:to="ions_ResearchAndDevelopmentExpensesMember_lbl" xlink:title="label: ResearchAndDevelopmentExpensesMember to ions_ResearchAndDevelopmentExpensesMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_ResearchAndDevelopmentExpensesMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_ResearchAndDevelopmentExpensesMember_lbl1" xml:lang="en-US" id="ions_ResearchAndDevelopmentExpensesMember_lbl1">Research and Development Expenses [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ResearchAndDevelopmentExpensesMember" xlink:to="ions_ResearchAndDevelopmentExpensesMember_lbl1" xlink:title="label: ResearchAndDevelopmentExpensesMember to ions_ResearchAndDevelopmentExpensesMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_ResearchAndDevelopmentExpensesMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_ResearchAndDevelopmentExpensesMember_lbl2" xml:lang="en-US" id="ions_ResearchAndDevelopmentExpensesMember_lbl2">R&amp;D Expenses [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ResearchAndDevelopmentExpensesMember" xlink:to="ions_ResearchAndDevelopmentExpensesMember_lbl2" xlink:title="label: ResearchAndDevelopmentExpensesMember to ions_ResearchAndDevelopmentExpensesMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20201231.xsd#ions_AkceaAcquisitionEmployeeSeveranceMember" xlink:label="AkceaAcquisitionEmployeeSeveranceMember" xlink:title="AkceaAcquisitionEmployeeSeveranceMember" />
    <link:label xlink:type="resource" xlink:label="ions_AkceaAcquisitionEmployeeSeveranceMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_AkceaAcquisitionEmployeeSeveranceMember_lbl" xml:lang="en-US" id="ions_AkceaAcquisitionEmployeeSeveranceMember_lbl">Termination of an employee as part of the Akcea Acquisition.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AkceaAcquisitionEmployeeSeveranceMember" xlink:to="ions_AkceaAcquisitionEmployeeSeveranceMember_lbl" xlink:title="label: AkceaAcquisitionEmployeeSeveranceMember to ions_AkceaAcquisitionEmployeeSeveranceMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_AkceaAcquisitionEmployeeSeveranceMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_AkceaAcquisitionEmployeeSeveranceMember_lbl1" xml:lang="en-US" id="ions_AkceaAcquisitionEmployeeSeveranceMember_lbl1">Akcea Acquisition, Employee Severance [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AkceaAcquisitionEmployeeSeveranceMember" xlink:to="ions_AkceaAcquisitionEmployeeSeveranceMember_lbl1" xlink:title="label: AkceaAcquisitionEmployeeSeveranceMember to ions_AkceaAcquisitionEmployeeSeveranceMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_AkceaAcquisitionEmployeeSeveranceMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_AkceaAcquisitionEmployeeSeveranceMember_lbl2" xml:lang="en-US" id="ions_AkceaAcquisitionEmployeeSeveranceMember_lbl2">Severance Related to Akcea Acquisition [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AkceaAcquisitionEmployeeSeveranceMember" xlink:to="ions_AkceaAcquisitionEmployeeSeveranceMember_lbl2" xlink:title="label: AkceaAcquisitionEmployeeSeveranceMember to ions_AkceaAcquisitionEmployeeSeveranceMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20201231.xsd#ions_ConsolidationLessThanWhollyOwnedSubsidiaryParentOwnershipInterestChangesPurchaseOfInterestByParentShares" xlink:label="ConsolidationLessThanWhollyOwnedSubsidiaryParentOwnershipInterestChangesPurchaseOfInterestByParentShares" xlink:title="ConsolidationLessThanWhollyOwnedSubsidiaryParentOwnershipInterestChangesPurchaseOfInterestByParentShares" />
    <link:label xlink:type="resource" xlink:label="ions_ConsolidationLessThanWhollyOwnedSubsidiaryParentOwnershipInterestChangesPurchaseOfInterestByParentShares_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_ConsolidationLessThanWhollyOwnedSubsidiaryParentOwnershipInterestChangesPurchaseOfInterestByParentShares_lbl" xml:lang="en-US" id="ions_ConsolidationLessThanWhollyOwnedSubsidiaryParentOwnershipInterestChangesPurchaseOfInterestByParentShares_lbl">Number of shares of the subsidiary purchased by the parent during the period, thereby effecting a change in total (consolidated) equity attributable to the parent.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConsolidationLessThanWhollyOwnedSubsidiaryParentOwnershipInterestChangesPurchaseOfInterestByParentShares" xlink:to="ions_ConsolidationLessThanWhollyOwnedSubsidiaryParentOwnershipInterestChangesPurchaseOfInterestByParentShares_lbl" xlink:title="label: ConsolidationLessThanWhollyOwnedSubsidiaryParentOwnershipInterestChangesPurchaseOfInterestByParentShares to ions_ConsolidationLessThanWhollyOwnedSubsidiaryParentOwnershipInterestChangesPurchaseOfInterestByParentShares_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_ConsolidationLessThanWhollyOwnedSubsidiaryParentOwnershipInterestChangesPurchaseOfInterestByParentShares_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_ConsolidationLessThanWhollyOwnedSubsidiaryParentOwnershipInterestChangesPurchaseOfInterestByParentShares_lbl1" xml:lang="en-US" id="ions_ConsolidationLessThanWhollyOwnedSubsidiaryParentOwnershipInterestChangesPurchaseOfInterestByParentShares_lbl1">Consolidation, Less than Wholly Owned Subsidiary, Parent Ownership Interest, Changes, Purchase of Interest by Parent, Shares</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConsolidationLessThanWhollyOwnedSubsidiaryParentOwnershipInterestChangesPurchaseOfInterestByParentShares" xlink:to="ions_ConsolidationLessThanWhollyOwnedSubsidiaryParentOwnershipInterestChangesPurchaseOfInterestByParentShares_lbl1" xlink:title="label: ConsolidationLessThanWhollyOwnedSubsidiaryParentOwnershipInterestChangesPurchaseOfInterestByParentShares to ions_ConsolidationLessThanWhollyOwnedSubsidiaryParentOwnershipInterestChangesPurchaseOfInterestByParentShares_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_ConsolidationLessThanWhollyOwnedSubsidiaryParentOwnershipInterestChangesPurchaseOfInterestByParentShares_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_ConsolidationLessThanWhollyOwnedSubsidiaryParentOwnershipInterestChangesPurchaseOfInterestByParentShares_lbl2" xml:lang="en-US" id="ions_ConsolidationLessThanWhollyOwnedSubsidiaryParentOwnershipInterestChangesPurchaseOfInterestByParentShares_lbl2">Shares purchased (in shares)</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConsolidationLessThanWhollyOwnedSubsidiaryParentOwnershipInterestChangesPurchaseOfInterestByParentShares" xlink:to="ions_ConsolidationLessThanWhollyOwnedSubsidiaryParentOwnershipInterestChangesPurchaseOfInterestByParentShares_lbl2" xlink:title="label: ConsolidationLessThanWhollyOwnedSubsidiaryParentOwnershipInterestChangesPurchaseOfInterestByParentShares to ions_ConsolidationLessThanWhollyOwnedSubsidiaryParentOwnershipInterestChangesPurchaseOfInterestByParentShares_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20201231.xsd#ions_PaymentsForCancelledEquityAwards" xlink:label="PaymentsForCancelledEquityAwards" xlink:title="PaymentsForCancelledEquityAwards" />
    <link:label xlink:type="resource" xlink:label="ions_PaymentsForCancelledEquityAwards_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_PaymentsForCancelledEquityAwards_lbl" xml:lang="en-US" id="ions_PaymentsForCancelledEquityAwards_lbl">The aggregate amount paid by the entity to cancel subsidiary's outstanding equity awards.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PaymentsForCancelledEquityAwards" xlink:to="ions_PaymentsForCancelledEquityAwards_lbl" xlink:title="label: PaymentsForCancelledEquityAwards to ions_PaymentsForCancelledEquityAwards_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_PaymentsForCancelledEquityAwards_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_PaymentsForCancelledEquityAwards_lbl1" xml:lang="en-US" id="ions_PaymentsForCancelledEquityAwards_lbl1">Payments for cancelled equity awards</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PaymentsForCancelledEquityAwards" xlink:to="ions_PaymentsForCancelledEquityAwards_lbl1" xlink:title="label: PaymentsForCancelledEquityAwards to ions_PaymentsForCancelledEquityAwards_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_PaymentsForCancelledEquityAwards_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_PaymentsForCancelledEquityAwards_lbl2" xml:lang="en-US" id="ions_PaymentsForCancelledEquityAwards_lbl2">Payments for cancelled equity awards</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PaymentsForCancelledEquityAwards" xlink:to="ions_PaymentsForCancelledEquityAwards_lbl2" xlink:title="label: PaymentsForCancelledEquityAwards to ions_PaymentsForCancelledEquityAwards_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20201231.xsd#ions_BiogenIncMember" xlink:label="BiogenIncMember" xlink:title="BiogenIncMember" />
    <link:label xlink:type="resource" xlink:label="ions_BiogenIncMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_BiogenIncMember_lbl" xml:lang="en-US" id="ions_BiogenIncMember_lbl">Biogen Inc. is an American multinational biotechnology company.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="BiogenIncMember" xlink:to="ions_BiogenIncMember_lbl" xlink:title="label: BiogenIncMember to ions_BiogenIncMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_BiogenIncMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_BiogenIncMember_lbl1" xml:lang="en-US" id="ions_BiogenIncMember_lbl1">Biogen Inc. [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="BiogenIncMember" xlink:to="ions_BiogenIncMember_lbl1" xlink:title="label: BiogenIncMember to ions_BiogenIncMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_BiogenIncMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_BiogenIncMember_lbl2" xml:lang="en-US" id="ions_BiogenIncMember_lbl2">Biogen [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="BiogenIncMember" xlink:to="ions_BiogenIncMember_lbl2" xlink:title="label: BiogenIncMember to ions_BiogenIncMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20201231.xsd#ions_NumberOfAgreementsWithCollaborationPartner" xlink:label="NumberOfAgreementsWithCollaborationPartner" xlink:title="NumberOfAgreementsWithCollaborationPartner" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfAgreementsWithCollaborationPartner_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_NumberOfAgreementsWithCollaborationPartner_lbl" xml:lang="en-US" id="ions_NumberOfAgreementsWithCollaborationPartner_lbl">The number of agreements entered into with the collaboration partner.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfAgreementsWithCollaborationPartner" xlink:to="ions_NumberOfAgreementsWithCollaborationPartner_lbl" xlink:title="label: NumberOfAgreementsWithCollaborationPartner to ions_NumberOfAgreementsWithCollaborationPartner_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfAgreementsWithCollaborationPartner_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_NumberOfAgreementsWithCollaborationPartner_lbl1" xml:lang="en-US" id="ions_NumberOfAgreementsWithCollaborationPartner_lbl1">Number of agreements with collaboration partner</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfAgreementsWithCollaborationPartner" xlink:to="ions_NumberOfAgreementsWithCollaborationPartner_lbl1" xlink:title="label: NumberOfAgreementsWithCollaborationPartner to ions_NumberOfAgreementsWithCollaborationPartner_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfAgreementsWithCollaborationPartner_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_NumberOfAgreementsWithCollaborationPartner_lbl2" xml:lang="en-US" id="ions_NumberOfAgreementsWithCollaborationPartner_lbl2">Number of agreements</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfAgreementsWithCollaborationPartner" xlink:to="ions_NumberOfAgreementsWithCollaborationPartner_lbl2" xlink:title="label: NumberOfAgreementsWithCollaborationPartner to ions_NumberOfAgreementsWithCollaborationPartner_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20201231.xsd#ions_RevenueFromContractWithCustomerTransactionPriceAdditions" xlink:label="RevenueFromContractWithCustomerTransactionPriceAdditions" xlink:title="RevenueFromContractWithCustomerTransactionPriceAdditions" />
    <link:label xlink:type="resource" xlink:label="ions_RevenueFromContractWithCustomerTransactionPriceAdditions_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_RevenueFromContractWithCustomerTransactionPriceAdditions_lbl" xml:lang="en-US" id="ions_RevenueFromContractWithCustomerTransactionPriceAdditions_lbl">The additional amount of consideration the Company earned under the collaboration agreement that is added to the transaction price.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RevenueFromContractWithCustomerTransactionPriceAdditions" xlink:to="ions_RevenueFromContractWithCustomerTransactionPriceAdditions_lbl" xlink:title="label: RevenueFromContractWithCustomerTransactionPriceAdditions to ions_RevenueFromContractWithCustomerTransactionPriceAdditions_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_RevenueFromContractWithCustomerTransactionPriceAdditions_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_RevenueFromContractWithCustomerTransactionPriceAdditions_lbl1" xml:lang="en-US" id="ions_RevenueFromContractWithCustomerTransactionPriceAdditions_lbl1">Revenue from Contract with Customer, Transaction Price, Additions</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RevenueFromContractWithCustomerTransactionPriceAdditions" xlink:to="ions_RevenueFromContractWithCustomerTransactionPriceAdditions_lbl1" xlink:title="label: RevenueFromContractWithCustomerTransactionPriceAdditions to ions_RevenueFromContractWithCustomerTransactionPriceAdditions_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_RevenueFromContractWithCustomerTransactionPriceAdditions_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_RevenueFromContractWithCustomerTransactionPriceAdditions_lbl2" xml:lang="en-US" id="ions_RevenueFromContractWithCustomerTransactionPriceAdditions_lbl2">Milestone payment received and added to transaction price</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RevenueFromContractWithCustomerTransactionPriceAdditions" xlink:to="ions_RevenueFromContractWithCustomerTransactionPriceAdditions_lbl2" xlink:title="label: RevenueFromContractWithCustomerTransactionPriceAdditions to ions_RevenueFromContractWithCustomerTransactionPriceAdditions_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20201231.xsd#ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2004WithAlnylamPharmaceuticalsIncMember" xlink:label="CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2004WithAlnylamPharmaceuticalsIncMember" xlink:title="CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2004WithAlnylamPharmaceuticalsIncMember" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2004WithAlnylamPharmaceuticalsIncMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2004WithAlnylamPharmaceuticalsIncMember_lbl" xml:lang="en-US" id="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2004WithAlnylamPharmaceuticalsIncMember_lbl">Represents information pertaining to the collaborative arrangement 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="CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2004WithAlnylamPharmaceuticalsIncMember" xlink:to="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2004WithAlnylamPharmaceuticalsIncMember_lbl" xlink:title="label: CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2004WithAlnylamPharmaceuticalsIncMember to ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2004WithAlnylamPharmaceuticalsIncMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2004WithAlnylamPharmaceuticalsIncMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2004WithAlnylamPharmaceuticalsIncMember_lbl1" xml:lang="en-US" id="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2004WithAlnylamPharmaceuticalsIncMember_lbl1">Collaborative Arrangement and Licensing Agreement Entered Into in March 2004 with Alnylam Pharmaceuticals, Inc. [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2004WithAlnylamPharmaceuticalsIncMember" xlink:to="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2004WithAlnylamPharmaceuticalsIncMember_lbl1" xlink:title="label: CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2004WithAlnylamPharmaceuticalsIncMember to ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2004WithAlnylamPharmaceuticalsIncMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2004WithAlnylamPharmaceuticalsIncMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2004WithAlnylamPharmaceuticalsIncMember_lbl2" xml:lang="en-US" id="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2004WithAlnylamPharmaceuticalsIncMember_lbl2">Alnylam [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2004WithAlnylamPharmaceuticalsIncMember" xlink:to="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2004WithAlnylamPharmaceuticalsIncMember_lbl2" xlink:title="label: CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2004WithAlnylamPharmaceuticalsIncMember to ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2004WithAlnylamPharmaceuticalsIncMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20201231.xsd#ions_RevenueFromContractWithCustomerNumberOfPerformanceObligationsAtInceptionOfContract" xlink:label="RevenueFromContractWithCustomerNumberOfPerformanceObligationsAtInceptionOfContract" xlink:title="RevenueFromContractWithCustomerNumberOfPerformanceObligationsAtInceptionOfContract" />
    <link:label xlink:type="resource" xlink:label="ions_RevenueFromContractWithCustomerNumberOfPerformanceObligationsAtInceptionOfContract_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_RevenueFromContractWithCustomerNumberOfPerformanceObligationsAtInceptionOfContract_lbl" xml:lang="en-US" id="ions_RevenueFromContractWithCustomerNumberOfPerformanceObligationsAtInceptionOfContract_lbl">The number of performance obligations at the inception of a contract.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RevenueFromContractWithCustomerNumberOfPerformanceObligationsAtInceptionOfContract" xlink:to="ions_RevenueFromContractWithCustomerNumberOfPerformanceObligationsAtInceptionOfContract_lbl" xlink:title="label: RevenueFromContractWithCustomerNumberOfPerformanceObligationsAtInceptionOfContract to ions_RevenueFromContractWithCustomerNumberOfPerformanceObligationsAtInceptionOfContract_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_RevenueFromContractWithCustomerNumberOfPerformanceObligationsAtInceptionOfContract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_RevenueFromContractWithCustomerNumberOfPerformanceObligationsAtInceptionOfContract_lbl1" xml:lang="en-US" id="ions_RevenueFromContractWithCustomerNumberOfPerformanceObligationsAtInceptionOfContract_lbl1">Revenue from Contract with Customer, Number of performance obligations at inception of contract</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RevenueFromContractWithCustomerNumberOfPerformanceObligationsAtInceptionOfContract" xlink:to="ions_RevenueFromContractWithCustomerNumberOfPerformanceObligationsAtInceptionOfContract_lbl1" xlink:title="label: RevenueFromContractWithCustomerNumberOfPerformanceObligationsAtInceptionOfContract to ions_RevenueFromContractWithCustomerNumberOfPerformanceObligationsAtInceptionOfContract_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_RevenueFromContractWithCustomerNumberOfPerformanceObligationsAtInceptionOfContract_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_RevenueFromContractWithCustomerNumberOfPerformanceObligationsAtInceptionOfContract_lbl2" xml:lang="en-US" id="ions_RevenueFromContractWithCustomerNumberOfPerformanceObligationsAtInceptionOfContract_lbl2">Number of performance obligations at inception of contract</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RevenueFromContractWithCustomerNumberOfPerformanceObligationsAtInceptionOfContract" xlink:to="ions_RevenueFromContractWithCustomerNumberOfPerformanceObligationsAtInceptionOfContract_lbl2" xlink:title="label: RevenueFromContractWithCustomerNumberOfPerformanceObligationsAtInceptionOfContract to ions_RevenueFromContractWithCustomerNumberOfPerformanceObligationsAtInceptionOfContract_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20201231.xsd#ions_TegsediMember" xlink:label="TegsediMember" xlink:title="TegsediMember" />
    <link:label xlink:type="resource" xlink:label="ions_TegsediMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_TegsediMember_lbl" xml:lang="en-US" id="ions_TegsediMember_lbl">TEGSEDI (inotersen) is a Generation 2+ antisense drug to treat people with hereditary TTR amyloidosis, or hATTR, a rare, progressive, fatal disease.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="TegsediMember" xlink:to="ions_TegsediMember_lbl" xlink:title="label: TegsediMember to ions_TegsediMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_TegsediMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_TegsediMember_lbl1" xml:lang="en-US" id="ions_TegsediMember_lbl1">TEGSEDI [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="TegsediMember" xlink:to="ions_TegsediMember_lbl1" xlink:title="label: TegsediMember to ions_TegsediMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_TegsediMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_TegsediMember_lbl2" xml:lang="en-US" id="ions_TegsediMember_lbl2">TEGSEDI [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="TegsediMember" xlink:to="ions_TegsediMember_lbl2" xlink:title="label: TegsediMember to ions_TegsediMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20201231.xsd#ions_MaximumPaymentReceivableUnderLicenseAgreement" xlink:label="MaximumPaymentReceivableUnderLicenseAgreement" xlink:title="MaximumPaymentReceivableUnderLicenseAgreement" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumPaymentReceivableUnderLicenseAgreement_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_MaximumPaymentReceivableUnderLicenseAgreement_lbl" xml:lang="en-US" id="ions_MaximumPaymentReceivableUnderLicenseAgreement_lbl">The maximum amount of payments expected to be received under the license agreement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumPaymentReceivableUnderLicenseAgreement" xlink:to="ions_MaximumPaymentReceivableUnderLicenseAgreement_lbl" xlink:title="label: MaximumPaymentReceivableUnderLicenseAgreement to ions_MaximumPaymentReceivableUnderLicenseAgreement_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumPaymentReceivableUnderLicenseAgreement_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_MaximumPaymentReceivableUnderLicenseAgreement_lbl1" xml:lang="en-US" id="ions_MaximumPaymentReceivableUnderLicenseAgreement_lbl1">Maximum payment receivable under license agreement</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumPaymentReceivableUnderLicenseAgreement" xlink:to="ions_MaximumPaymentReceivableUnderLicenseAgreement_lbl1" xlink:title="label: MaximumPaymentReceivableUnderLicenseAgreement to ions_MaximumPaymentReceivableUnderLicenseAgreement_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumPaymentReceivableUnderLicenseAgreement_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_MaximumPaymentReceivableUnderLicenseAgreement_lbl2" xml:lang="en-US" id="ions_MaximumPaymentReceivableUnderLicenseAgreement_lbl2">Maximum payment receivable under license agreement</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumPaymentReceivableUnderLicenseAgreement" xlink:to="ions_MaximumPaymentReceivableUnderLicenseAgreement_lbl2" xlink:title="label: MaximumPaymentReceivableUnderLicenseAgreement to ions_MaximumPaymentReceivableUnderLicenseAgreement_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20201231.xsd#ions_WaylivraMember" xlink:label="WaylivraMember" xlink:title="WaylivraMember" />
    <link:label xlink:type="resource" xlink:label="ions_WaylivraMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_WaylivraMember_lbl" xml:lang="en-US" id="ions_WaylivraMember_lbl">WAYLIVRA is a drug designed to treat two severe and rare, genetically defined diseases, familial chylomicronemia syndrome, or FCS, and familial partial lipodystrophy, or FPL.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="WaylivraMember" xlink:to="ions_WaylivraMember_lbl" xlink:title="label: WaylivraMember to ions_WaylivraMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_WaylivraMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_WaylivraMember_lbl1" xml:lang="en-US" id="ions_WaylivraMember_lbl1">WAYLIVRA [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="WaylivraMember" xlink:to="ions_WaylivraMember_lbl1" xlink:title="label: WaylivraMember to ions_WaylivraMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_WaylivraMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_WaylivraMember_lbl2" xml:lang="en-US" id="ions_WaylivraMember_lbl2">WAYLIVRA [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="WaylivraMember" xlink:to="ions_WaylivraMember_lbl2" xlink:title="label: WaylivraMember to ions_WaylivraMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20201231.xsd#ions_PeriodBeforeCollaborationPartnerPaysRoyaltiesOnNetSalesOfProductAfterFirstCommercialSaleInBrazil" xlink:label="PeriodBeforeCollaborationPartnerPaysRoyaltiesOnNetSalesOfProductAfterFirstCommercialSaleInBrazil" xlink:title="PeriodBeforeCollaborationPartnerPaysRoyaltiesOnNetSalesOfProductAfterFirstCommercialSaleInBrazil" />
    <link:label xlink:type="resource" xlink:label="ions_PeriodBeforeCollaborationPartnerPaysRoyaltiesOnNetSalesOfProductAfterFirstCommercialSaleInBrazil_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_PeriodBeforeCollaborationPartnerPaysRoyaltiesOnNetSalesOfProductAfterFirstCommercialSaleInBrazil_lbl" xml:lang="en-US" id="ions_PeriodBeforeCollaborationPartnerPaysRoyaltiesOnNetSalesOfProductAfterFirstCommercialSaleInBrazil_lbl">Period of time before collaboration partner pays royalties on net sales of product after first commercial sale in Brazil, 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="PeriodBeforeCollaborationPartnerPaysRoyaltiesOnNetSalesOfProductAfterFirstCommercialSaleInBrazil" xlink:to="ions_PeriodBeforeCollaborationPartnerPaysRoyaltiesOnNetSalesOfProductAfterFirstCommercialSaleInBrazil_lbl" xlink:title="label: PeriodBeforeCollaborationPartnerPaysRoyaltiesOnNetSalesOfProductAfterFirstCommercialSaleInBrazil to ions_PeriodBeforeCollaborationPartnerPaysRoyaltiesOnNetSalesOfProductAfterFirstCommercialSaleInBrazil_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_PeriodBeforeCollaborationPartnerPaysRoyaltiesOnNetSalesOfProductAfterFirstCommercialSaleInBrazil_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_PeriodBeforeCollaborationPartnerPaysRoyaltiesOnNetSalesOfProductAfterFirstCommercialSaleInBrazil_lbl1" xml:lang="en-US" id="ions_PeriodBeforeCollaborationPartnerPaysRoyaltiesOnNetSalesOfProductAfterFirstCommercialSaleInBrazil_lbl1">Period before collaboration partner pays royalties on net sales of product after first commercial sale in Brazil</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PeriodBeforeCollaborationPartnerPaysRoyaltiesOnNetSalesOfProductAfterFirstCommercialSaleInBrazil" xlink:to="ions_PeriodBeforeCollaborationPartnerPaysRoyaltiesOnNetSalesOfProductAfterFirstCommercialSaleInBrazil_lbl1" xlink:title="label: PeriodBeforeCollaborationPartnerPaysRoyaltiesOnNetSalesOfProductAfterFirstCommercialSaleInBrazil to ions_PeriodBeforeCollaborationPartnerPaysRoyaltiesOnNetSalesOfProductAfterFirstCommercialSaleInBrazil_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_PeriodBeforeCollaborationPartnerPaysRoyaltiesOnNetSalesOfProductAfterFirstCommercialSaleInBrazil_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_PeriodBeforeCollaborationPartnerPaysRoyaltiesOnNetSalesOfProductAfterFirstCommercialSaleInBrazil_lbl2" xml:lang="en-US" id="ions_PeriodBeforeCollaborationPartnerPaysRoyaltiesOnNetSalesOfProductAfterFirstCommercialSaleInBrazil_lbl2">Period before PTC pays royalties on net sales of product after first commercial sale in Brazil</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PeriodBeforeCollaborationPartnerPaysRoyaltiesOnNetSalesOfProductAfterFirstCommercialSaleInBrazil" xlink:to="ions_PeriodBeforeCollaborationPartnerPaysRoyaltiesOnNetSalesOfProductAfterFirstCommercialSaleInBrazil_lbl2" xlink:title="label: PeriodBeforeCollaborationPartnerPaysRoyaltiesOnNetSalesOfProductAfterFirstCommercialSaleInBrazil to ions_PeriodBeforeCollaborationPartnerPaysRoyaltiesOnNetSalesOfProductAfterFirstCommercialSaleInBrazil_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20201231.xsd#ions_RoyaltyPercentageReceivedOnNetSalesOfEachDrugInLatinAmericaFromCollaborationPartner" xlink:label="RoyaltyPercentageReceivedOnNetSalesOfEachDrugInLatinAmericaFromCollaborationPartner" xlink:title="RoyaltyPercentageReceivedOnNetSalesOfEachDrugInLatinAmericaFromCollaborationPartner" />
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    <link:loc xlink:type="locator" xlink:href="ions-20201231.xsd#ions_RevenueRecognizedByCollaborationPartnerInLatinAmericaBeforePayingRoyalties" xlink:label="RevenueRecognizedByCollaborationPartnerInLatinAmericaBeforePayingRoyalties" xlink:title="RevenueRecognizedByCollaborationPartnerInLatinAmericaBeforePayingRoyalties" />
    <link:label xlink:type="resource" xlink:label="ions_RevenueRecognizedByCollaborationPartnerInLatinAmericaBeforePayingRoyalties_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_RevenueRecognizedByCollaborationPartnerInLatinAmericaBeforePayingRoyalties_lbl" xml:lang="en-US" id="ions_RevenueRecognizedByCollaborationPartnerInLatinAmericaBeforePayingRoyalties_lbl">The minimum amount of revenue recognized in Latin America by the collaboration partner before paying royalties.</link:label>
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    <link:label xlink:type="resource" xlink:label="ions_RevenueRecognizedByCollaborationPartnerInLatinAmericaBeforePayingRoyalties_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_RevenueRecognizedByCollaborationPartnerInLatinAmericaBeforePayingRoyalties_lbl1" xml:lang="en-US" id="ions_RevenueRecognizedByCollaborationPartnerInLatinAmericaBeforePayingRoyalties_lbl1">Revenue recognized by collaboration partner in Latin America before paying royalties</link:label>
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    <link:label xlink:type="resource" xlink:label="ions_RevenueRecognizedByCollaborationPartnerInLatinAmericaBeforePayingRoyalties_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_RevenueRecognizedByCollaborationPartnerInLatinAmericaBeforePayingRoyalties_lbl2" xml:lang="en-US" id="ions_RevenueRecognizedByCollaborationPartnerInLatinAmericaBeforePayingRoyalties_lbl2">Minimum revenue recognized in Latin America by PTC before paying royalties</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RevenueRecognizedByCollaborationPartnerInLatinAmericaBeforePayingRoyalties" xlink:to="ions_RevenueRecognizedByCollaborationPartnerInLatinAmericaBeforePayingRoyalties_lbl2" xlink:title="label: RevenueRecognizedByCollaborationPartnerInLatinAmericaBeforePayingRoyalties to ions_RevenueRecognizedByCollaborationPartnerInLatinAmericaBeforePayingRoyalties_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20201231.xsd#ions_PotentialPremiumReceivedIfCommonStockIsPurchasedInFuture" xlink:label="PotentialPremiumReceivedIfCommonStockIsPurchasedInFuture" xlink:title="PotentialPremiumReceivedIfCommonStockIsPurchasedInFuture" />
    <link:label xlink:type="resource" xlink:label="ions_PotentialPremiumReceivedIfCommonStockIsPurchasedInFuture_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_PotentialPremiumReceivedIfCommonStockIsPurchasedInFuture_lbl" xml:lang="en-US" id="ions_PotentialPremiumReceivedIfCommonStockIsPurchasedInFuture_lbl">The potential premium received if common stock is purchased in the future under a Stock Purchase Agreement (SPA) in conjunction with the collaboration agreement.</link:label>
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    <link:label xlink:type="resource" xlink:label="ions_PotentialPremiumReceivedIfCommonStockIsPurchasedInFuture_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_PotentialPremiumReceivedIfCommonStockIsPurchasedInFuture_lbl2" xml:lang="en-US" id="ions_PotentialPremiumReceivedIfCommonStockIsPurchasedInFuture_lbl2">Potential premium received if common stock is purchased in the future</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PotentialPremiumReceivedIfCommonStockIsPurchasedInFuture" xlink:to="ions_PotentialPremiumReceivedIfCommonStockIsPurchasedInFuture_lbl2" xlink:title="label: PotentialPremiumReceivedIfCommonStockIsPurchasedInFuture to ions_PotentialPremiumReceivedIfCommonStockIsPurchasedInFuture_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20201231.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-20201231.xsd#ions_MaximumAmountOfPaymentsReceivableForMilestones" xlink:label="MaximumAmountOfPaymentsReceivableForMilestones" xlink:title="MaximumAmountOfPaymentsReceivableForMilestones" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfPaymentsReceivableForMilestones_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_MaximumAmountOfPaymentsReceivableForMilestones_lbl" xml:lang="en-US" id="ions_MaximumAmountOfPaymentsReceivableForMilestones_lbl">The maximum amount of payments receivable for milestones under the collaboration agreement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfPaymentsReceivableForMilestones" xlink:to="ions_MaximumAmountOfPaymentsReceivableForMilestones_lbl" xlink:title="label: MaximumAmountOfPaymentsReceivableForMilestones to ions_MaximumAmountOfPaymentsReceivableForMilestones_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfPaymentsReceivableForMilestones_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_MaximumAmountOfPaymentsReceivableForMilestones_lbl1" xml:lang="en-US" id="ions_MaximumAmountOfPaymentsReceivableForMilestones_lbl1">Maximum amount of payments receivable for milestones</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfPaymentsReceivableForMilestones" xlink:to="ions_MaximumAmountOfPaymentsReceivableForMilestones_lbl1" xlink:title="label: MaximumAmountOfPaymentsReceivableForMilestones to ions_MaximumAmountOfPaymentsReceivableForMilestones_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfPaymentsReceivableForMilestones_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_MaximumAmountOfPaymentsReceivableForMilestones_lbl2" xml:lang="en-US" id="ions_MaximumAmountOfPaymentsReceivableForMilestones_lbl2">Maximum amount of payments receivable for milestones</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfPaymentsReceivableForMilestones" xlink:to="ions_MaximumAmountOfPaymentsReceivableForMilestones_lbl2" xlink:title="label: MaximumAmountOfPaymentsReceivableForMilestones to ions_MaximumAmountOfPaymentsReceivableForMilestones_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20201231.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 PelacarsenL, 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-20201231.xsd#ions_AdditionalAmountOfCommonStockRequiredToBePurchased" xlink:label="AdditionalAmountOfCommonStockRequiredToBePurchased" xlink:title="AdditionalAmountOfCommonStockRequiredToBePurchased" />
    <link:label xlink:type="resource" xlink:label="ions_AdditionalAmountOfCommonStockRequiredToBePurchased_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_AdditionalAmountOfCommonStockRequiredToBePurchased_lbl" xml:lang="en-US" id="ions_AdditionalAmountOfCommonStockRequiredToBePurchased_lbl">The additional amount of common stock the collaboration partner is required to purchase under a Stock Purchase Agreement (SPA) in conjunction with the collaboration agreement.</link:label>
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    <link:label xlink:type="resource" xlink:label="ions_AdditionalAmountOfCommonStockRequiredToBePurchased_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_AdditionalAmountOfCommonStockRequiredToBePurchased_lbl1" xml:lang="en-US" id="ions_AdditionalAmountOfCommonStockRequiredToBePurchased_lbl1">Additional amount of common stock required to be purchased</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AdditionalAmountOfCommonStockRequiredToBePurchased" xlink:to="ions_AdditionalAmountOfCommonStockRequiredToBePurchased_lbl1" xlink:title="label: AdditionalAmountOfCommonStockRequiredToBePurchased to ions_AdditionalAmountOfCommonStockRequiredToBePurchased_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_AdditionalAmountOfCommonStockRequiredToBePurchased_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_AdditionalAmountOfCommonStockRequiredToBePurchased_lbl2" xml:lang="en-US" id="ions_AdditionalAmountOfCommonStockRequiredToBePurchased_lbl2">Additional amount of common stock required to be purchased</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AdditionalAmountOfCommonStockRequiredToBePurchased" xlink:to="ions_AdditionalAmountOfCommonStockRequiredToBePurchased_lbl2" xlink:title="label: AdditionalAmountOfCommonStockRequiredToBePurchased to ions_AdditionalAmountOfCommonStockRequiredToBePurchased_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20201231.xsd#ions_ResearchAndDevelopmentServicesForIonisApociiiLMember" xlink:label="ResearchAndDevelopmentServicesForIonisApociiiLMember" xlink:title="ResearchAndDevelopmentServicesForIonisApociiiLMember" />
    <link:label xlink:type="resource" xlink:label="ions_ResearchAndDevelopmentServicesForIonisApociiiLMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_ResearchAndDevelopmentServicesForIonisApociiiLMember_lbl" xml:lang="en-US" id="ions_ResearchAndDevelopmentServicesForIonisApociiiLMember_lbl">Research and development (R&amp;D) services for IONIS-APOCIII-L, an antisense therapy with the potential to significantly reduce cardiovascular risk in patients suffering from high levels of the lipoprotein ApoCIII.</link:label>
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    <link:label xlink:type="resource" xlink:label="ions_ResearchAndDevelopmentServicesForIonisApociiiLMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_ResearchAndDevelopmentServicesForIonisApociiiLMember_lbl1" xml:lang="en-US" id="ions_ResearchAndDevelopmentServicesForIonisApociiiLMember_lbl1">Research and Development Services for Ionis-Apociii-L [Member]</link:label>
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    <link:label xlink:type="resource" xlink:label="ions_ResearchAndDevelopmentServicesForIonisApociiiLMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_ResearchAndDevelopmentServicesForIonisApociiiLMember_lbl2" xml:lang="en-US" id="ions_ResearchAndDevelopmentServicesForIonisApociiiLMember_lbl2">R&amp;D Services for IONIS-APOCIII-L [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ResearchAndDevelopmentServicesForIonisApociiiLMember" xlink:to="ions_ResearchAndDevelopmentServicesForIonisApociiiLMember_lbl2" xlink:title="label: ResearchAndDevelopmentServicesForIonisApociiiLMember to ions_ResearchAndDevelopmentServicesForIonisApociiiLMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20201231.xsd#ions_IonisApociiiLActivePharmaceuticalIngredientMember" xlink:label="IonisApociiiLActivePharmaceuticalIngredientMember" xlink:title="IonisApociiiLActivePharmaceuticalIngredientMember" />
    <link:label xlink:type="resource" xlink:label="ions_IonisApociiiLActivePharmaceuticalIngredientMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_IonisApociiiLActivePharmaceuticalIngredientMember_lbl" xml:lang="en-US" id="ions_IonisApociiiLActivePharmaceuticalIngredientMember_lbl">The active pharmaceutical ingredient, or API, for IONIS-APOCIII-L, 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="IonisApociiiLActivePharmaceuticalIngredientMember" xlink:to="ions_IonisApociiiLActivePharmaceuticalIngredientMember_lbl" xlink:title="label: IonisApociiiLActivePharmaceuticalIngredientMember to ions_IonisApociiiLActivePharmaceuticalIngredientMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_IonisApociiiLActivePharmaceuticalIngredientMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_IonisApociiiLActivePharmaceuticalIngredientMember_lbl1" xml:lang="en-US" id="ions_IonisApociiiLActivePharmaceuticalIngredientMember_lbl1">Ionis-Apociii-L Active Pharmaceutical Ingredient [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IonisApociiiLActivePharmaceuticalIngredientMember" xlink:to="ions_IonisApociiiLActivePharmaceuticalIngredientMember_lbl1" xlink:title="label: IonisApociiiLActivePharmaceuticalIngredientMember to ions_IonisApociiiLActivePharmaceuticalIngredientMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_IonisApociiiLActivePharmaceuticalIngredientMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_IonisApociiiLActivePharmaceuticalIngredientMember_lbl2" xml:lang="en-US" id="ions_IonisApociiiLActivePharmaceuticalIngredientMember_lbl2">IONIS-APOCIII-L API [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IonisApociiiLActivePharmaceuticalIngredientMember" xlink:to="ions_IonisApociiiLActivePharmaceuticalIngredientMember_lbl2" xlink:title="label: IonisApociiiLActivePharmaceuticalIngredientMember to ions_IonisApociiiLActivePharmaceuticalIngredientMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20201231.xsd#ions_RoyaltyPercentageReceivedOnSalesOfDrug" xlink:label="RoyaltyPercentageReceivedOnSalesOfDrug" xlink:title="RoyaltyPercentageReceivedOnSalesOfDrug" />
    <link:label xlink:type="resource" xlink:label="ions_RoyaltyPercentageReceivedOnSalesOfDrug_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_RoyaltyPercentageReceivedOnSalesOfDrug_lbl" xml:lang="en-US" id="ions_RoyaltyPercentageReceivedOnSalesOfDrug_lbl">Royalty percentage received on the sales of a drug 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="RoyaltyPercentageReceivedOnSalesOfDrug" xlink:to="ions_RoyaltyPercentageReceivedOnSalesOfDrug_lbl" xlink:title="label: RoyaltyPercentageReceivedOnSalesOfDrug to ions_RoyaltyPercentageReceivedOnSalesOfDrug_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_RoyaltyPercentageReceivedOnSalesOfDrug_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_RoyaltyPercentageReceivedOnSalesOfDrug_lbl1" xml:lang="en-US" id="ions_RoyaltyPercentageReceivedOnSalesOfDrug_lbl1">Royalty percentage received on sales of drug</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RoyaltyPercentageReceivedOnSalesOfDrug" xlink:to="ions_RoyaltyPercentageReceivedOnSalesOfDrug_lbl1" xlink:title="label: RoyaltyPercentageReceivedOnSalesOfDrug to ions_RoyaltyPercentageReceivedOnSalesOfDrug_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_RoyaltyPercentageReceivedOnSalesOfDrug_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_RoyaltyPercentageReceivedOnSalesOfDrug_lbl2" xml:lang="en-US" id="ions_RoyaltyPercentageReceivedOnSalesOfDrug_lbl2">Royalty percentage received on sales of drug</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RoyaltyPercentageReceivedOnSalesOfDrug" xlink:to="ions_RoyaltyPercentageReceivedOnSalesOfDrug_lbl2" xlink:title="label: RoyaltyPercentageReceivedOnSalesOfDrug to ions_RoyaltyPercentageReceivedOnSalesOfDrug_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20201231.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-20201231.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-20201231.xsd#ions_Ion449Member" xlink:label="Ion449Member" xlink:title="Ion449Member" />
    <link:label xlink:type="resource" xlink:label="ions_Ion449Member_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_Ion449Member_lbl" xml:lang="en-US" id="ions_Ion449Member_lbl">ION449 (formerly IONIS-AZ4-2.5-LRx), also known as AZD8233, is a ligand-conjugated (LICA) investigational antisense medicine designed to reduce plasma levels of proprotein convertase subtilisin/kexin type 9 (PCSK9).</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="Ion449Member" xlink:to="ions_Ion449Member_lbl" xlink:title="label: Ion449Member to ions_Ion449Member_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_Ion449Member_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_Ion449Member_lbl1" xml:lang="en-US" id="ions_Ion449Member_lbl1">Ion449 [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="Ion449Member" xlink:to="ions_Ion449Member_lbl1" xlink:title="label: Ion449Member to ions_Ion449Member_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_Ion449Member_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_Ion449Member_lbl2" xml:lang="en-US" id="ions_Ion449Member_lbl2">ION449[Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="Ion449Member" xlink:to="ions_Ion449Member_lbl2" xlink:title="label: Ion449Member to ions_Ion449Member_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20201231.xsd#ions_Ion532AndIon449Member" xlink:label="Ion532AndIon449Member" xlink:title="Ion532AndIon449Member" />
    <link:label xlink:type="resource" xlink:label="ions_Ion532AndIon449Member_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_Ion532AndIon449Member_lbl" xml:lang="en-US" id="ions_Ion532AndIon449Member_lbl">ION532 (formerly IONIS-AZ5-2.5Rx ), also known as AZD2373, is an investigational antisense medicine designed to reduce the production of apolipoprotein L1 (APOL1) for the treatment of APOL1-associated chronic kidney disease (CKD). ION449 (formerly IONIS-AZ4-2.5-LRx), also known as AZD8233, is a ligand-conjugated (LICA) investigational antisense medicine designed to reduce plasma levels of proprotein convertase subtilisin/kexin type 9 (PCSK9).</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="Ion532AndIon449Member" xlink:to="ions_Ion532AndIon449Member_lbl" xlink:title="label: Ion532AndIon449Member to ions_Ion532AndIon449Member_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_Ion532AndIon449Member_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_Ion532AndIon449Member_lbl1" xml:lang="en-US" id="ions_Ion532AndIon449Member_lbl1">Ion532 and Ion449 [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="Ion532AndIon449Member" xlink:to="ions_Ion532AndIon449Member_lbl1" xlink:title="label: Ion532AndIon449Member to ions_Ion532AndIon449Member_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_Ion532AndIon449Member_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_Ion532AndIon449Member_lbl2" xml:lang="en-US" id="ions_Ion532AndIon449Member_lbl2">ION532 and ION449 [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="Ion532AndIon449Member" xlink:to="ions_Ion532AndIon449Member_lbl2" xlink:title="label: Ion532AndIon449Member to ions_Ion532AndIon449Member_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20201231.xsd#ions_Ion455Member" xlink:label="Ion455Member" xlink:title="Ion455Member" />
    <link:label xlink:type="resource" xlink:label="ions_Ion455Member_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_Ion455Member_lbl" xml:lang="en-US" id="ions_Ion455Member_lbl">An investigational antisense medicine being developed as a potential treatment for nonalcoholic steatohepatitis (NASH).</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="Ion455Member" xlink:to="ions_Ion455Member_lbl" xlink:title="label: Ion455Member to ions_Ion455Member_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_Ion455Member_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_Ion455Member_lbl1" xml:lang="en-US" id="ions_Ion455Member_lbl1">Ion455 [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="Ion455Member" xlink:to="ions_Ion455Member_lbl1" xlink:title="label: Ion455Member to ions_Ion455Member_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_Ion455Member_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_Ion455Member_lbl2" xml:lang="en-US" id="ions_Ion455Member_lbl2">ION455 [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="Ion455Member" xlink:to="ions_Ion455Member_lbl2" xlink:title="label: Ion455Member to ions_Ion455Member_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20201231.xsd#ions_Ion532Member" xlink:label="Ion532Member" xlink:title="Ion532Member" />
    <link:label xlink:type="resource" xlink:label="ions_Ion532Member_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_Ion532Member_lbl" xml:lang="en-US" id="ions_Ion532Member_lbl">A drug designed to treat a genetically associated form of kidney disease.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="Ion532Member" xlink:to="ions_Ion532Member_lbl" xlink:title="label: Ion532Member to ions_Ion532Member_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_Ion532Member_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_Ion532Member_lbl1" xml:lang="en-US" id="ions_Ion532Member_lbl1">Ion532 [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="Ion532Member" xlink:to="ions_Ion532Member_lbl1" xlink:title="label: Ion532Member to ions_Ion532Member_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_Ion532Member_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_Ion532Member_lbl2" xml:lang="en-US" id="ions_Ion532Member_lbl2">ION532 [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="Ion532Member" xlink:to="ions_Ion532Member_lbl2" xlink:title="label: Ion532Member to ions_Ion532Member_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20201231.xsd#ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJuly2015WithAstrazenecaMember" xlink:label="CollaborativeArrangementAndLicensingAgreementEnteredIntoInJuly2015WithAstrazenecaMember" xlink:title="CollaborativeArrangementAndLicensingAgreementEnteredIntoInJuly2015WithAstrazenecaMember" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJuly2015WithAstrazenecaMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJuly2015WithAstrazenecaMember_lbl" xml:lang="en-US" id="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJuly2015WithAstrazenecaMember_lbl">Represents information pertaining to the collaborative arrangement 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="CollaborativeArrangementAndLicensingAgreementEnteredIntoInJuly2015WithAstrazenecaMember" xlink:to="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJuly2015WithAstrazenecaMember_lbl" xlink:title="label: CollaborativeArrangementAndLicensingAgreementEnteredIntoInJuly2015WithAstrazenecaMember to ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJuly2015WithAstrazenecaMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJuly2015WithAstrazenecaMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJuly2015WithAstrazenecaMember_lbl1" xml:lang="en-US" id="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJuly2015WithAstrazenecaMember_lbl1">Collaborative Arrangement and Licensing Agreement Entered Into in July 2015 with AstraZeneca [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementAndLicensingAgreementEnteredIntoInJuly2015WithAstrazenecaMember" xlink:to="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJuly2015WithAstrazenecaMember_lbl1" xlink:title="label: CollaborativeArrangementAndLicensingAgreementEnteredIntoInJuly2015WithAstrazenecaMember to ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJuly2015WithAstrazenecaMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJuly2015WithAstrazenecaMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJuly2015WithAstrazenecaMember_lbl2" xml:lang="en-US" id="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJuly2015WithAstrazenecaMember_lbl2">AstraZeneca [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementAndLicensingAgreementEnteredIntoInJuly2015WithAstrazenecaMember" xlink:to="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJuly2015WithAstrazenecaMember_lbl2" xlink:title="label: CollaborativeArrangementAndLicensingAgreementEnteredIntoInJuly2015WithAstrazenecaMember to ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJuly2015WithAstrazenecaMember_lbl2" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJuly2015WithAstrazenecaMember_lbl3" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJuly2015WithAstrazenecaMember_lbl3" xml:lang="en-US" id="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJuly2015WithAstrazenecaMember_lbl3">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="CollaborativeArrangementAndLicensingAgreementEnteredIntoInJuly2015WithAstrazenecaMember" xlink:to="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJuly2015WithAstrazenecaMember_lbl3" xlink:title="label: CollaborativeArrangementAndLicensingAgreementEnteredIntoInJuly2015WithAstrazenecaMember to ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJuly2015WithAstrazenecaMember_lbl3" />
    <link:loc xlink:type="locator" xlink:href="ions-20201231.xsd#ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithAstrazenecaMember" xlink:label="CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithAstrazenecaMember" xlink:title="CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithAstrazenecaMember" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithAstrazenecaMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithAstrazenecaMember_lbl" xml:lang="en-US" id="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithAstrazenecaMember_lbl">Represents information pertaining to the collaborative arrangement entered into with AstraZeneca PLC in December 2012 and amended in January 2016 to discover and develop antisense drugs for cancer.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithAstrazenecaMember" xlink:to="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithAstrazenecaMember_lbl" xlink:title="label: CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithAstrazenecaMember to ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithAstrazenecaMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithAstrazenecaMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithAstrazenecaMember_lbl1" xml:lang="en-US" id="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithAstrazenecaMember_lbl1">Collaborative Arrangement and Licensing Agreement Entered Into in December 2012 with AstraZeneca [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithAstrazenecaMember" xlink:to="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithAstrazenecaMember_lbl1" xlink:title="label: CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithAstrazenecaMember to ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithAstrazenecaMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithAstrazenecaMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithAstrazenecaMember_lbl2" xml:lang="en-US" id="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithAstrazenecaMember_lbl2">Oncology [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithAstrazenecaMember" xlink:to="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithAstrazenecaMember_lbl2" xlink:title="label: CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithAstrazenecaMember to ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithAstrazenecaMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20201231.xsd#ions_NumberOfLicensedMedicines" xlink:label="NumberOfLicensedMedicines" xlink:title="NumberOfLicensedMedicines" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfLicensedMedicines_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_NumberOfLicensedMedicines_lbl" xml:lang="en-US" id="ions_NumberOfLicensedMedicines_lbl">The number of medicines that have been licensed under the collaboration agreement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfLicensedMedicines" xlink:to="ions_NumberOfLicensedMedicines_lbl" xlink:title="label: NumberOfLicensedMedicines to ions_NumberOfLicensedMedicines_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfLicensedMedicines_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_NumberOfLicensedMedicines_lbl1" xml:lang="en-US" id="ions_NumberOfLicensedMedicines_lbl1">Number of licensed medicines</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfLicensedMedicines" xlink:to="ions_NumberOfLicensedMedicines_lbl1" xlink:title="label: NumberOfLicensedMedicines to ions_NumberOfLicensedMedicines_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfLicensedMedicines_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_NumberOfLicensedMedicines_lbl2" xml:lang="en-US" id="ions_NumberOfLicensedMedicines_lbl2">Number of licensed medicines</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfLicensedMedicines" xlink:to="ions_NumberOfLicensedMedicines_lbl2" xlink:title="label: NumberOfLicensedMedicines to ions_NumberOfLicensedMedicines_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20201231.xsd#ions_NumberOfProgramsAdvanced" xlink:label="NumberOfProgramsAdvanced" xlink:title="NumberOfProgramsAdvanced" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfProgramsAdvanced_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_NumberOfProgramsAdvanced_lbl" xml:lang="en-US" id="ions_NumberOfProgramsAdvanced_lbl">The number of programs advanced under the collaboration agreement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfProgramsAdvanced" xlink:to="ions_NumberOfProgramsAdvanced_lbl" xlink:title="label: NumberOfProgramsAdvanced to ions_NumberOfProgramsAdvanced_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfProgramsAdvanced_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_NumberOfProgramsAdvanced_lbl1" xml:lang="en-US" id="ions_NumberOfProgramsAdvanced_lbl1">Number of programs advanced</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfProgramsAdvanced" xlink:to="ions_NumberOfProgramsAdvanced_lbl1" xlink:title="label: NumberOfProgramsAdvanced to ions_NumberOfProgramsAdvanced_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfProgramsAdvanced_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_NumberOfProgramsAdvanced_lbl2" xml:lang="en-US" id="ions_NumberOfProgramsAdvanced_lbl2">Number of programs advanced</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfProgramsAdvanced" xlink:to="ions_NumberOfProgramsAdvanced_lbl2" xlink:title="label: NumberOfProgramsAdvanced to ions_NumberOfProgramsAdvanced_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20201231.xsd#ions_Ion839Member" xlink:label="Ion839Member" xlink:title="Ion839Member" />
    <link:label xlink:type="resource" xlink:label="ions_Ion839Member_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_Ion839Member_lbl" xml:lang="en-US" id="ions_Ion839Member_lbl">A drug designed to inhibit an undisclosed target to treat patients with nonalcoholic steatohepatitis, or NASH.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="Ion839Member" xlink:to="ions_Ion839Member_lbl" xlink:title="label: Ion839Member to ions_Ion839Member_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_Ion839Member_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_Ion839Member_lbl1" xml:lang="en-US" id="ions_Ion839Member_lbl1">Ion839 [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="Ion839Member" xlink:to="ions_Ion839Member_lbl1" xlink:title="label: Ion839Member to ions_Ion839Member_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_Ion839Member_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_Ion839Member_lbl2" xml:lang="en-US" id="ions_Ion839Member_lbl2">ION839 [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="Ion839Member" xlink:to="ions_Ion839Member_lbl2" xlink:title="label: Ion839Member to ions_Ion839Member_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20201231.xsd#ions_NumberOfCollaborationAgreements" xlink:label="NumberOfCollaborationAgreements" xlink:title="NumberOfCollaborationAgreements" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfCollaborationAgreements_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_NumberOfCollaborationAgreements_lbl" xml:lang="en-US" id="ions_NumberOfCollaborationAgreements_lbl">The number of collaboration agreements with the collaboration partner.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfCollaborationAgreements" xlink:to="ions_NumberOfCollaborationAgreements_lbl" xlink:title="label: NumberOfCollaborationAgreements to ions_NumberOfCollaborationAgreements_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfCollaborationAgreements_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_NumberOfCollaborationAgreements_lbl1" xml:lang="en-US" id="ions_NumberOfCollaborationAgreements_lbl1">Number of collaboration agreements</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfCollaborationAgreements" xlink:to="ions_NumberOfCollaborationAgreements_lbl1" xlink:title="label: NumberOfCollaborationAgreements to ions_NumberOfCollaborationAgreements_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfCollaborationAgreements_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_NumberOfCollaborationAgreements_lbl2" xml:lang="en-US" id="ions_NumberOfCollaborationAgreements_lbl2">Number of collaboration agreements</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfCollaborationAgreements" xlink:to="ions_NumberOfCollaborationAgreements_lbl2" xlink:title="label: NumberOfCollaborationAgreements to ions_NumberOfCollaborationAgreements_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20201231.xsd#ions_NumberOfLicenseFeesEarned" xlink:label="NumberOfLicenseFeesEarned" xlink:title="NumberOfLicenseFeesEarned" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfLicenseFeesEarned_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_NumberOfLicenseFeesEarned_lbl" xml:lang="en-US" id="ions_NumberOfLicenseFeesEarned_lbl">The number of license fees earned 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="NumberOfLicenseFeesEarned" xlink:to="ions_NumberOfLicenseFeesEarned_lbl" xlink:title="label: NumberOfLicenseFeesEarned to ions_NumberOfLicenseFeesEarned_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfLicenseFeesEarned_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_NumberOfLicenseFeesEarned_lbl1" xml:lang="en-US" id="ions_NumberOfLicenseFeesEarned_lbl1">Number of license fees earned</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfLicenseFeesEarned" xlink:to="ions_NumberOfLicenseFeesEarned_lbl1" xlink:title="label: NumberOfLicenseFeesEarned to ions_NumberOfLicenseFeesEarned_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfLicenseFeesEarned_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_NumberOfLicenseFeesEarned_lbl2" xml:lang="en-US" id="ions_NumberOfLicenseFeesEarned_lbl2">Number of license fees earned</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfLicenseFeesEarned" xlink:to="ions_NumberOfLicenseFeesEarned_lbl2" xlink:title="label: NumberOfLicenseFeesEarned to ions_NumberOfLicenseFeesEarned_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20201231.xsd#ions_DanvatirsenMember" xlink:label="DanvatirsenMember" xlink:title="DanvatirsenMember" />
    <link:label xlink:type="resource" xlink:label="ions_DanvatirsenMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_DanvatirsenMember_lbl" xml:lang="en-US" id="ions_DanvatirsenMember_lbl">Danvatirsen (formerly IONIS-STAT3-2.5, also known as AZD9150) was designed to treat cancer by inhibiting the production of a gene critical for tumor cell growth and survival. Signal transducer and activator of transcription 3, or STAT3, is over-active in a variety of cancers, including brain, lung, breast, bone, liver and multiple myeloma and promotes tumor cell growth and prevents cell death.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DanvatirsenMember" xlink:to="ions_DanvatirsenMember_lbl" xlink:title="label: DanvatirsenMember to ions_DanvatirsenMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_DanvatirsenMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_DanvatirsenMember_lbl1" xml:lang="en-US" id="ions_DanvatirsenMember_lbl1">Danvatirsen [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DanvatirsenMember" xlink:to="ions_DanvatirsenMember_lbl1" xlink:title="label: DanvatirsenMember to ions_DanvatirsenMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_DanvatirsenMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_DanvatirsenMember_lbl2" xml:lang="en-US" id="ions_DanvatirsenMember_lbl2">Danvatirsen [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DanvatirsenMember" xlink:to="ions_DanvatirsenMember_lbl2" xlink:title="label: DanvatirsenMember to ions_DanvatirsenMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20201231.xsd#ions_Ion736Member" xlink:label="Ion736Member" xlink:title="Ion736Member" />
    <link:label xlink:type="resource" xlink:label="ions_Ion736Member_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_Ion736Member_lbl" xml:lang="en-US" id="ions_Ion736Member_lbl">ION736, formerly known as IONIS-AZ7-2.5, is a Generation 2.5 antisense drug.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="Ion736Member" xlink:to="ions_Ion736Member_lbl" xlink:title="label: Ion736Member to ions_Ion736Member_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_Ion736Member_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_Ion736Member_lbl1" xml:lang="en-US" id="ions_Ion736Member_lbl1">Ion736 [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="Ion736Member" xlink:to="ions_Ion736Member_lbl1" xlink:title="label: Ion736Member to ions_Ion736Member_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_Ion736Member_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_Ion736Member_lbl2" xml:lang="en-US" id="ions_Ion736Member_lbl2">ION736 [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="Ion736Member" xlink:to="ions_Ion736Member_lbl2" xlink:title="label: Ion736Member to ions_Ion736Member_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20201231.xsd#ions_NumberOfCountriesWhereDrugIsApprovedForUse" xlink:label="NumberOfCountriesWhereDrugIsApprovedForUse" xlink:title="NumberOfCountriesWhereDrugIsApprovedForUse" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfCountriesWhereDrugIsApprovedForUse_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_NumberOfCountriesWhereDrugIsApprovedForUse_lbl" xml:lang="en-US" id="ions_NumberOfCountriesWhereDrugIsApprovedForUse_lbl">The number of countries where the drug is approved for treatment in patients.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfCountriesWhereDrugIsApprovedForUse" xlink:to="ions_NumberOfCountriesWhereDrugIsApprovedForUse_lbl" xlink:title="label: NumberOfCountriesWhereDrugIsApprovedForUse to ions_NumberOfCountriesWhereDrugIsApprovedForUse_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfCountriesWhereDrugIsApprovedForUse_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_NumberOfCountriesWhereDrugIsApprovedForUse_lbl1" xml:lang="en-US" id="ions_NumberOfCountriesWhereDrugIsApprovedForUse_lbl1">Number of countries where drug is approved for use</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfCountriesWhereDrugIsApprovedForUse" xlink:to="ions_NumberOfCountriesWhereDrugIsApprovedForUse_lbl1" xlink:title="label: NumberOfCountriesWhereDrugIsApprovedForUse to ions_NumberOfCountriesWhereDrugIsApprovedForUse_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfCountriesWhereDrugIsApprovedForUse_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_NumberOfCountriesWhereDrugIsApprovedForUse_lbl2" xml:lang="en-US" id="ions_NumberOfCountriesWhereDrugIsApprovedForUse_lbl2">Number of countries where SPINRAZA is approved for use</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfCountriesWhereDrugIsApprovedForUse" xlink:to="ions_NumberOfCountriesWhereDrugIsApprovedForUse_lbl2" xlink:title="label: NumberOfCountriesWhereDrugIsApprovedForUse to ions_NumberOfCountriesWhereDrugIsApprovedForUse_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20201231.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-20201231.xsd#ions_MaximumAmountOfPaymentsReceivablePerDrugOrProgramForRegulatoryMilestones" xlink:label="MaximumAmountOfPaymentsReceivablePerDrugOrProgramForRegulatoryMilestones" xlink:title="MaximumAmountOfPaymentsReceivablePerDrugOrProgramForRegulatoryMilestones" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfPaymentsReceivablePerDrugOrProgramForRegulatoryMilestones_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_MaximumAmountOfPaymentsReceivablePerDrugOrProgramForRegulatoryMilestones_lbl" xml:lang="en-US" id="ions_MaximumAmountOfPaymentsReceivablePerDrugOrProgramForRegulatoryMilestones_lbl">The maximum amount of payments receivable per drug or program for regulatory milestone payments under the collaboration agreement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfPaymentsReceivablePerDrugOrProgramForRegulatoryMilestones" xlink:to="ions_MaximumAmountOfPaymentsReceivablePerDrugOrProgramForRegulatoryMilestones_lbl" xlink:title="label: MaximumAmountOfPaymentsReceivablePerDrugOrProgramForRegulatoryMilestones to ions_MaximumAmountOfPaymentsReceivablePerDrugOrProgramForRegulatoryMilestones_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfPaymentsReceivablePerDrugOrProgramForRegulatoryMilestones_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_MaximumAmountOfPaymentsReceivablePerDrugOrProgramForRegulatoryMilestones_lbl1" xml:lang="en-US" id="ions_MaximumAmountOfPaymentsReceivablePerDrugOrProgramForRegulatoryMilestones_lbl1">Maximum amount of payments receivable per drug or program for regulatory milestones</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfPaymentsReceivablePerDrugOrProgramForRegulatoryMilestones" xlink:to="ions_MaximumAmountOfPaymentsReceivablePerDrugOrProgramForRegulatoryMilestones_lbl1" xlink:title="label: MaximumAmountOfPaymentsReceivablePerDrugOrProgramForRegulatoryMilestones to ions_MaximumAmountOfPaymentsReceivablePerDrugOrProgramForRegulatoryMilestones_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfPaymentsReceivablePerDrugOrProgramForRegulatoryMilestones_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_MaximumAmountOfPaymentsReceivablePerDrugOrProgramForRegulatoryMilestones_lbl2" xml:lang="en-US" id="ions_MaximumAmountOfPaymentsReceivablePerDrugOrProgramForRegulatoryMilestones_lbl2">Maximum amount of payments receivable per program for regulatory milestones</link:label>
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    <link:loc xlink:type="locator" xlink:href="ions-20201231.xsd#ions_NumberOfMedicinesBeingDeveloped" xlink:label="NumberOfMedicinesBeingDeveloped" xlink:title="NumberOfMedicinesBeingDeveloped" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfMedicinesBeingDeveloped_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_NumberOfMedicinesBeingDeveloped_lbl" xml:lang="en-US" id="ions_NumberOfMedicinesBeingDeveloped_lbl">The number of medicines currently being developed under the collaboration agreement(s).</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfMedicinesBeingDeveloped" xlink:to="ions_NumberOfMedicinesBeingDeveloped_lbl" xlink:title="label: NumberOfMedicinesBeingDeveloped to ions_NumberOfMedicinesBeingDeveloped_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfMedicinesBeingDeveloped_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_NumberOfMedicinesBeingDeveloped_lbl1" xml:lang="en-US" id="ions_NumberOfMedicinesBeingDeveloped_lbl1">Number of medicines being developed</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfMedicinesBeingDeveloped" xlink:to="ions_NumberOfMedicinesBeingDeveloped_lbl1" xlink:title="label: NumberOfMedicinesBeingDeveloped to ions_NumberOfMedicinesBeingDeveloped_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfMedicinesBeingDeveloped_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_NumberOfMedicinesBeingDeveloped_lbl2" xml:lang="en-US" id="ions_NumberOfMedicinesBeingDeveloped_lbl2">Number of medicines currently being developed</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfMedicinesBeingDeveloped" xlink:to="ions_NumberOfMedicinesBeingDeveloped_lbl2" xlink:title="label: NumberOfMedicinesBeingDeveloped to ions_NumberOfMedicinesBeingDeveloped_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20201231.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-20201231.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>
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    <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-20201231.xsd#ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2017WithBiogenMember" xlink:label="CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2017WithBiogenMember" xlink:title="CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2017WithBiogenMember" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2017WithBiogenMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2017WithBiogenMember_lbl" xml:lang="en-US" id="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2017WithBiogenMember_lbl">Represents information pertaining to the collaborative arrangement 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="CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2017WithBiogenMember" xlink:to="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2017WithBiogenMember_lbl" xlink:title="label: CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2017WithBiogenMember to ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2017WithBiogenMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2017WithBiogenMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2017WithBiogenMember_lbl1" xml:lang="en-US" id="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2017WithBiogenMember_lbl1">Collaborative Arrangement and Licensing Agreement Entered Into in December 2017 with Biogen [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2017WithBiogenMember" xlink:to="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2017WithBiogenMember_lbl1" xlink:title="label: CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2017WithBiogenMember to ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2017WithBiogenMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2017WithBiogenMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2017WithBiogenMember_lbl2" xml:lang="en-US" id="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2017WithBiogenMember_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="CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2017WithBiogenMember" xlink:to="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2017WithBiogenMember_lbl2" xlink:title="label: CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2017WithBiogenMember to ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2017WithBiogenMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20201231.xsd#ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2012WithBiogenMember" xlink:label="CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2012WithBiogenMember" xlink:title="CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2012WithBiogenMember" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2012WithBiogenMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2012WithBiogenMember_lbl" xml:lang="en-US" id="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2012WithBiogenMember_lbl">Represents information pertaining to the collaborative arrangement 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="CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2012WithBiogenMember" xlink:to="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2012WithBiogenMember_lbl" xlink:title="label: CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2012WithBiogenMember to ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2012WithBiogenMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2012WithBiogenMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2012WithBiogenMember_lbl1" xml:lang="en-US" id="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2012WithBiogenMember_lbl1">Collaborative Arrangement and Licensing Agreement Entered Into in January 2012 with Biogen [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2012WithBiogenMember" xlink:to="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2012WithBiogenMember_lbl1" xlink:title="label: CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2012WithBiogenMember to ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2012WithBiogenMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2012WithBiogenMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2012WithBiogenMember_lbl2" xml:lang="en-US" id="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2012WithBiogenMember_lbl2">SPINRAZA [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2012WithBiogenMember" xlink:to="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2012WithBiogenMember_lbl2" xlink:title="label: CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2012WithBiogenMember to ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2012WithBiogenMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20201231.xsd#ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember" xlink:label="CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember" xlink:title="CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember_lbl" xml:lang="en-US" id="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember_lbl">Represents information pertaining to the collaborative arrangement entered into with Biogen Inc. in September 2013. This agreement is a long-term strategic relationship focused on applying antisense technology to advance the treatment of neurodegenerative diseases (Strategic Neurology).</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember" xlink:to="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember_lbl" xlink:title="label: CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember to ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember_lbl1" xml:lang="en-US" id="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember_lbl1">Collaborative Arrangement and Licensing Agreement Entered Into in September 2013 with Biogen [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember" xlink:to="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember_lbl1" xlink:title="label: CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember to ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember_lbl2" xml:lang="en-US" id="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember_lbl2">2013 Strategic Neurology [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember" xlink:to="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember_lbl2" xlink:title="label: CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember to ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember_lbl2" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember_lbl3" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember_lbl3" xml:lang="en-US" id="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember_lbl3">Biogen 2013 Strategic Neurology [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember" xlink:to="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember_lbl3" xlink:title="label: CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember to ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember_lbl3" />
    <link:loc xlink:type="locator" xlink:href="ions-20201231.xsd#ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember" xlink:label="CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember" xlink:title="CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember_lbl" xml:lang="en-US" id="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember_lbl">Represents information pertaining to the expanded collaborative arrangement 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="CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember" xlink:to="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember_lbl" xlink:title="label: CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember to ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember_lbl1" xml:lang="en-US" id="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember_lbl1">Collaborative Arrangement and Licensing Agreement Entered Into in April 2018 with Biogen [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember" xlink:to="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember_lbl1" xlink:title="label: CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember to ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember_lbl2" xml:lang="en-US" id="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember_lbl2">Biogen 2018 Strategic Neurology [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember" xlink:to="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember_lbl2" xlink:title="label: CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember to ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember_lbl2" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember_lbl3" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember_lbl3" xml:lang="en-US" id="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember_lbl3">2018 Strategic Neurology [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember" xlink:to="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember_lbl3" xlink:title="label: CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember to ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember_lbl3" />
    <link:loc xlink:type="locator" xlink:href="ions-20201231.xsd#ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember" xlink:label="CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember" xlink:title="CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember_lbl" xml:lang="en-US" id="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember_lbl">Represents information pertaining to the collaborative arrangement entered into with Biogen Inc. in December 2012. This agreement is focused on developing and commercializing novel antisense drugs for up to three targets to treat neurological or neuromuscular diseases (Neurology).</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember" xlink:to="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember_lbl" xlink:title="label: CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember to ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember_lbl1" xml:lang="en-US" id="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember_lbl1">Collaborative Arrangement and Licensing Agreement Entered Into in December 2012 with Biogen [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember" xlink:to="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember_lbl1" xlink:title="label: CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember to ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember_lbl2" xml:lang="en-US" id="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember_lbl2">2012 Neurology [Member]</link:label>
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    <link:loc xlink:type="locator" xlink:href="ions-20201231.xsd#ions_MaximumAmountOfPaymentsReceivablePerDrugOrProgramForLicenseFeesAndSubstantiveMilestonePayments" xlink:label="MaximumAmountOfPaymentsReceivablePerDrugOrProgramForLicenseFeesAndSubstantiveMilestonePayments" xlink:title="MaximumAmountOfPaymentsReceivablePerDrugOrProgramForLicenseFeesAndSubstantiveMilestonePayments" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfPaymentsReceivablePerDrugOrProgramForLicenseFeesAndSubstantiveMilestonePayments_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_MaximumAmountOfPaymentsReceivablePerDrugOrProgramForLicenseFeesAndSubstantiveMilestonePayments_lbl" xml:lang="en-US" id="ions_MaximumAmountOfPaymentsReceivablePerDrugOrProgramForLicenseFeesAndSubstantiveMilestonePayments_lbl">The maximum amount of payments receivable per drug or program for license fees and/or substantive milestone payments under the collaboration agreement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfPaymentsReceivablePerDrugOrProgramForLicenseFeesAndSubstantiveMilestonePayments" xlink:to="ions_MaximumAmountOfPaymentsReceivablePerDrugOrProgramForLicenseFeesAndSubstantiveMilestonePayments_lbl" xlink:title="label: MaximumAmountOfPaymentsReceivablePerDrugOrProgramForLicenseFeesAndSubstantiveMilestonePayments to ions_MaximumAmountOfPaymentsReceivablePerDrugOrProgramForLicenseFeesAndSubstantiveMilestonePayments_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfPaymentsReceivablePerDrugOrProgramForLicenseFeesAndSubstantiveMilestonePayments_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_MaximumAmountOfPaymentsReceivablePerDrugOrProgramForLicenseFeesAndSubstantiveMilestonePayments_lbl1" xml:lang="en-US" id="ions_MaximumAmountOfPaymentsReceivablePerDrugOrProgramForLicenseFeesAndSubstantiveMilestonePayments_lbl1">Maximum amount of payments receivable per drug or program for license fees and substantive milestone payments</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfPaymentsReceivablePerDrugOrProgramForLicenseFeesAndSubstantiveMilestonePayments" xlink:to="ions_MaximumAmountOfPaymentsReceivablePerDrugOrProgramForLicenseFeesAndSubstantiveMilestonePayments_lbl1" xlink:title="label: MaximumAmountOfPaymentsReceivablePerDrugOrProgramForLicenseFeesAndSubstantiveMilestonePayments to ions_MaximumAmountOfPaymentsReceivablePerDrugOrProgramForLicenseFeesAndSubstantiveMilestonePayments_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfPaymentsReceivablePerDrugOrProgramForLicenseFeesAndSubstantiveMilestonePayments_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_MaximumAmountOfPaymentsReceivablePerDrugOrProgramForLicenseFeesAndSubstantiveMilestonePayments_lbl2" xml:lang="en-US" id="ions_MaximumAmountOfPaymentsReceivablePerDrugOrProgramForLicenseFeesAndSubstantiveMilestonePayments_lbl2">Maximum amount of payments receivable per program for license fee and milestone payments</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfPaymentsReceivablePerDrugOrProgramForLicenseFeesAndSubstantiveMilestonePayments" xlink:to="ions_MaximumAmountOfPaymentsReceivablePerDrugOrProgramForLicenseFeesAndSubstantiveMilestonePayments_lbl2" xlink:title="label: MaximumAmountOfPaymentsReceivablePerDrugOrProgramForLicenseFeesAndSubstantiveMilestonePayments to ions_MaximumAmountOfPaymentsReceivablePerDrugOrProgramForLicenseFeesAndSubstantiveMilestonePayments_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20201231.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-20201231.xsd#ions_MaximumAmountOfPaymentsReceivableForSalesMilestones" xlink:label="MaximumAmountOfPaymentsReceivableForSalesMilestones" xlink:title="MaximumAmountOfPaymentsReceivableForSalesMilestones" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfPaymentsReceivableForSalesMilestones_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_MaximumAmountOfPaymentsReceivableForSalesMilestones_lbl" xml:lang="en-US" id="ions_MaximumAmountOfPaymentsReceivableForSalesMilestones_lbl">The maximum amount of payments receivable for sales milestones under the collaboration agreement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfPaymentsReceivableForSalesMilestones" xlink:to="ions_MaximumAmountOfPaymentsReceivableForSalesMilestones_lbl" xlink:title="label: MaximumAmountOfPaymentsReceivableForSalesMilestones to ions_MaximumAmountOfPaymentsReceivableForSalesMilestones_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfPaymentsReceivableForSalesMilestones_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_MaximumAmountOfPaymentsReceivableForSalesMilestones_lbl1" xml:lang="en-US" id="ions_MaximumAmountOfPaymentsReceivableForSalesMilestones_lbl1">Maximum amount of payments receivable for sales milestones</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfPaymentsReceivableForSalesMilestones" xlink:to="ions_MaximumAmountOfPaymentsReceivableForSalesMilestones_lbl1" xlink:title="label: MaximumAmountOfPaymentsReceivableForSalesMilestones to ions_MaximumAmountOfPaymentsReceivableForSalesMilestones_lbl1" />
    <link:loc xlink:type="locator" xlink:href="ions-20201231.xsd#ions_AntisenseMoleculeMember" xlink:label="AntisenseMoleculeMember" xlink:title="AntisenseMoleculeMember" />
    <link:label xlink:type="resource" xlink:label="ions_AntisenseMoleculeMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_AntisenseMoleculeMember_lbl" xml:lang="en-US" id="ions_AntisenseMoleculeMember_lbl">Each antisense molecule that is chosen for drug discovery and development to advance the treatment of neurological diseases.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AntisenseMoleculeMember" xlink:to="ions_AntisenseMoleculeMember_lbl" xlink:title="label: AntisenseMoleculeMember to ions_AntisenseMoleculeMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_AntisenseMoleculeMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_AntisenseMoleculeMember_lbl1" xml:lang="en-US" id="ions_AntisenseMoleculeMember_lbl1">Antisense Molecule [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AntisenseMoleculeMember" xlink:to="ions_AntisenseMoleculeMember_lbl1" xlink:title="label: AntisenseMoleculeMember to ions_AntisenseMoleculeMember_lbl1" />
    <link:loc xlink:type="locator" xlink:href="ions-20201231.xsd#ions_NumberOfProgramsUnderWhichDrugsAreToBeDevelopedAndCommercialized" xlink:label="NumberOfProgramsUnderWhichDrugsAreToBeDevelopedAndCommercialized" xlink:title="NumberOfProgramsUnderWhichDrugsAreToBeDevelopedAndCommercialized" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfProgramsUnderWhichDrugsAreToBeDevelopedAndCommercialized_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_NumberOfProgramsUnderWhichDrugsAreToBeDevelopedAndCommercialized_lbl" xml:lang="en-US" id="ions_NumberOfProgramsUnderWhichDrugsAreToBeDevelopedAndCommercialized_lbl">The number of programs under which drugs 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="NumberOfProgramsUnderWhichDrugsAreToBeDevelopedAndCommercialized" xlink:to="ions_NumberOfProgramsUnderWhichDrugsAreToBeDevelopedAndCommercialized_lbl" xlink:title="label: NumberOfProgramsUnderWhichDrugsAreToBeDevelopedAndCommercialized to ions_NumberOfProgramsUnderWhichDrugsAreToBeDevelopedAndCommercialized_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfProgramsUnderWhichDrugsAreToBeDevelopedAndCommercialized_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_NumberOfProgramsUnderWhichDrugsAreToBeDevelopedAndCommercialized_lbl1" xml:lang="en-US" id="ions_NumberOfProgramsUnderWhichDrugsAreToBeDevelopedAndCommercialized_lbl1">Number of programs under which drugs 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="NumberOfProgramsUnderWhichDrugsAreToBeDevelopedAndCommercialized" xlink:to="ions_NumberOfProgramsUnderWhichDrugsAreToBeDevelopedAndCommercialized_lbl1" xlink:title="label: NumberOfProgramsUnderWhichDrugsAreToBeDevelopedAndCommercialized to ions_NumberOfProgramsUnderWhichDrugsAreToBeDevelopedAndCommercialized_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfProgramsUnderWhichDrugsAreToBeDevelopedAndCommercialized_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_NumberOfProgramsUnderWhichDrugsAreToBeDevelopedAndCommercialized_lbl2" xml:lang="en-US" id="ions_NumberOfProgramsUnderWhichDrugsAreToBeDevelopedAndCommercialized_lbl2">Number of programs under which drugs 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="NumberOfProgramsUnderWhichDrugsAreToBeDevelopedAndCommercialized" xlink:to="ions_NumberOfProgramsUnderWhichDrugsAreToBeDevelopedAndCommercialized_lbl2" xlink:title="label: NumberOfProgramsUnderWhichDrugsAreToBeDevelopedAndCommercialized to ions_NumberOfProgramsUnderWhichDrugsAreToBeDevelopedAndCommercialized_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20201231.xsd#ions_MaximumAmountOfPaymentsReceivablePerDrugOrProgramForDevelopmentMilestones" xlink:label="MaximumAmountOfPaymentsReceivablePerDrugOrProgramForDevelopmentMilestones" xlink:title="MaximumAmountOfPaymentsReceivablePerDrugOrProgramForDevelopmentMilestones" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfPaymentsReceivablePerDrugOrProgramForDevelopmentMilestones_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_MaximumAmountOfPaymentsReceivablePerDrugOrProgramForDevelopmentMilestones_lbl" xml:lang="en-US" id="ions_MaximumAmountOfPaymentsReceivablePerDrugOrProgramForDevelopmentMilestones_lbl">The maximum amount of payments receivable per drug or program for development milestone payments under the collaboration agreement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfPaymentsReceivablePerDrugOrProgramForDevelopmentMilestones" xlink:to="ions_MaximumAmountOfPaymentsReceivablePerDrugOrProgramForDevelopmentMilestones_lbl" xlink:title="label: MaximumAmountOfPaymentsReceivablePerDrugOrProgramForDevelopmentMilestones to ions_MaximumAmountOfPaymentsReceivablePerDrugOrProgramForDevelopmentMilestones_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfPaymentsReceivablePerDrugOrProgramForDevelopmentMilestones_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_MaximumAmountOfPaymentsReceivablePerDrugOrProgramForDevelopmentMilestones_lbl1" xml:lang="en-US" id="ions_MaximumAmountOfPaymentsReceivablePerDrugOrProgramForDevelopmentMilestones_lbl1">Maximum amount of payments receivable per drug or program for development milestones</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfPaymentsReceivablePerDrugOrProgramForDevelopmentMilestones" xlink:to="ions_MaximumAmountOfPaymentsReceivablePerDrugOrProgramForDevelopmentMilestones_lbl1" xlink:title="label: MaximumAmountOfPaymentsReceivablePerDrugOrProgramForDevelopmentMilestones to ions_MaximumAmountOfPaymentsReceivablePerDrugOrProgramForDevelopmentMilestones_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfPaymentsReceivablePerDrugOrProgramForDevelopmentMilestones_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_MaximumAmountOfPaymentsReceivablePerDrugOrProgramForDevelopmentMilestones_lbl2" xml:lang="en-US" id="ions_MaximumAmountOfPaymentsReceivablePerDrugOrProgramForDevelopmentMilestones_lbl2">Maximum amount of payments receivable per program for development milestones</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfPaymentsReceivablePerDrugOrProgramForDevelopmentMilestones" xlink:to="ions_MaximumAmountOfPaymentsReceivablePerDrugOrProgramForDevelopmentMilestones_lbl2" xlink:title="label: MaximumAmountOfPaymentsReceivablePerDrugOrProgramForDevelopmentMilestones to ions_MaximumAmountOfPaymentsReceivablePerDrugOrProgramForDevelopmentMilestones_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20201231.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-20201231.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-20201231.xsd#ions_PercentageCashPremiumPaidOnSharesPurchased" xlink:label="PercentageCashPremiumPaidOnSharesPurchased" xlink:title="PercentageCashPremiumPaidOnSharesPurchased" />
    <link:label xlink:type="resource" xlink:label="ions_PercentageCashPremiumPaidOnSharesPurchased_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_PercentageCashPremiumPaidOnSharesPurchased_lbl" xml:lang="en-US" id="ions_PercentageCashPremiumPaidOnSharesPurchased_lbl">The percentage cash premium paid per share of the Company's common stock under the collaboration agreement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PercentageCashPremiumPaidOnSharesPurchased" xlink:to="ions_PercentageCashPremiumPaidOnSharesPurchased_lbl" xlink:title="label: PercentageCashPremiumPaidOnSharesPurchased to ions_PercentageCashPremiumPaidOnSharesPurchased_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_PercentageCashPremiumPaidOnSharesPurchased_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_PercentageCashPremiumPaidOnSharesPurchased_lbl1" xml:lang="en-US" id="ions_PercentageCashPremiumPaidOnSharesPurchased_lbl1">Percentage cash premium paid on shares purchased</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PercentageCashPremiumPaidOnSharesPurchased" xlink:to="ions_PercentageCashPremiumPaidOnSharesPurchased_lbl1" xlink:title="label: PercentageCashPremiumPaidOnSharesPurchased to ions_PercentageCashPremiumPaidOnSharesPurchased_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_PercentageCashPremiumPaidOnSharesPurchased_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_PercentageCashPremiumPaidOnSharesPurchased_lbl2" xml:lang="en-US" id="ions_PercentageCashPremiumPaidOnSharesPurchased_lbl2">Percentage cash premium paid on shares purchased</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PercentageCashPremiumPaidOnSharesPurchased" xlink:to="ions_PercentageCashPremiumPaidOnSharesPurchased_lbl2" xlink:title="label: PercentageCashPremiumPaidOnSharesPurchased to ions_PercentageCashPremiumPaidOnSharesPurchased_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20201231.xsd#ions_MedicinesForMultipleSystemAtrophyMember" xlink:label="MedicinesForMultipleSystemAtrophyMember" xlink:title="MedicinesForMultipleSystemAtrophyMember" />
    <link:label xlink:type="resource" xlink:label="ions_MedicinesForMultipleSystemAtrophyMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_MedicinesForMultipleSystemAtrophyMember_lbl" xml:lang="en-US" id="ions_MedicinesForMultipleSystemAtrophyMember_lbl">Medicines to treat multiple system atrophy (MSA), a progressive neurodegenerative disorder characterized by a combination of symptoms that affect both the autonomic nervous system and movement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MedicinesForMultipleSystemAtrophyMember" xlink:to="ions_MedicinesForMultipleSystemAtrophyMember_lbl" xlink:title="label: MedicinesForMultipleSystemAtrophyMember to ions_MedicinesForMultipleSystemAtrophyMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_MedicinesForMultipleSystemAtrophyMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_MedicinesForMultipleSystemAtrophyMember_lbl1" xml:lang="en-US" id="ions_MedicinesForMultipleSystemAtrophyMember_lbl1">Medicines for Multiple System Atrophy [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MedicinesForMultipleSystemAtrophyMember" xlink:to="ions_MedicinesForMultipleSystemAtrophyMember_lbl1" xlink:title="label: MedicinesForMultipleSystemAtrophyMember to ions_MedicinesForMultipleSystemAtrophyMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_MedicinesForMultipleSystemAtrophyMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_MedicinesForMultipleSystemAtrophyMember_lbl2" xml:lang="en-US" id="ions_MedicinesForMultipleSystemAtrophyMember_lbl2">Medicines for Multiple System Atrophy [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MedicinesForMultipleSystemAtrophyMember" xlink:to="ions_MedicinesForMultipleSystemAtrophyMember_lbl2" xlink:title="label: MedicinesForMultipleSystemAtrophyMember to ions_MedicinesForMultipleSystemAtrophyMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20201231.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-20201231.xsd#ions_Ion859Member" xlink:label="Ion859Member" xlink:title="Ion859Member" />
    <link:label xlink:type="resource" xlink:label="ions_Ion859Member_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_Ion859Member_lbl" xml:lang="en-US" id="ions_Ion859Member_lbl">ION859 (BIIB094) is an antisense medicine designed to inhibit the production of the Leucine Rich Repeat Kinase 2, or LRRK2, protein as a potential therapy for Parkinson's disease, or PD.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="Ion859Member" xlink:to="ions_Ion859Member_lbl" xlink:title="label: Ion859Member to ions_Ion859Member_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_Ion859Member_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_Ion859Member_lbl1" xml:lang="en-US" id="ions_Ion859Member_lbl1">Ion859 [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="Ion859Member" xlink:to="ions_Ion859Member_lbl1" xlink:title="label: Ion859Member to ions_Ion859Member_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_Ion859Member_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_Ion859Member_lbl2" xml:lang="en-US" id="ions_Ion859Member_lbl2">ION859 [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="Ion859Member" xlink:to="ions_Ion859Member_lbl2" xlink:title="label: Ion859Member to ions_Ion859Member_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20201231.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-20201231.xsd#ions_TofersenMember" xlink:label="TofersenMember" xlink:title="TofersenMember" />
    <link:label xlink:type="resource" xlink:label="ions_TofersenMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_TofersenMember_lbl" xml:lang="en-US" id="ions_TofersenMember_lbl">Tofersen (IONIS-SOD1Rx or BIIB067) is an antisense medicine designed to inhibit the production of superoxide dismutase 1, or SOD1, which is a well understood genetic cause of familial amyotrophic lateral sclerosis, or ALS.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="TofersenMember" xlink:to="ions_TofersenMember_lbl" xlink:title="label: TofersenMember to ions_TofersenMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_TofersenMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_TofersenMember_lbl1" xml:lang="en-US" id="ions_TofersenMember_lbl1">Tofersen [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="TofersenMember" xlink:to="ions_TofersenMember_lbl1" xlink:title="label: TofersenMember to ions_TofersenMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_TofersenMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_TofersenMember_lbl2" xml:lang="en-US" id="ions_TofersenMember_lbl2">Tofersen [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="TofersenMember" xlink:to="ions_TofersenMember_lbl2" xlink:title="label: TofersenMember to ions_TofersenMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20201231.xsd#ions_IonisC9Member" xlink:label="IonisC9Member" xlink:title="IonisC9Member" />
    <link:label xlink:type="resource" xlink:label="ions_IonisC9Member_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_IonisC9Member_lbl" xml:lang="en-US" id="ions_IonisC9Member_lbl">IONIS-C9Rx is an antisense medicine designed to selectively inhibit the production of the mutated chromosome 9 open reading frame 72, or C9ORF72, gene.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IonisC9Member" xlink:to="ions_IonisC9Member_lbl" xlink:title="label: IonisC9Member to ions_IonisC9Member_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_IonisC9Member_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_IonisC9Member_lbl1" xml:lang="en-US" id="ions_IonisC9Member_lbl1">Ionis-C9 [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IonisC9Member" xlink:to="ions_IonisC9Member_lbl1" xlink:title="label: IonisC9Member to ions_IonisC9Member_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_IonisC9Member_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_IonisC9Member_lbl2" xml:lang="en-US" id="ions_IonisC9Member_lbl2">IONIS-C9 [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IonisC9Member" xlink:to="ions_IonisC9Member_lbl2" xlink:title="label: IonisC9Member to ions_IonisC9Member_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20201231.xsd#ions_TermOfExtensionStudy" xlink:label="TermOfExtensionStudy" xlink:title="TermOfExtensionStudy" />
    <link:label xlink:type="resource" xlink:label="ions_TermOfExtensionStudy_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_TermOfExtensionStudy_lbl" xml:lang="en-US" id="ions_TermOfExtensionStudy_lbl">Term of long-term open label extension study, in which patients participating in double blind placebo controlled trials of new medications are invited, on completion of the initial trial, to take the study drug for some further period, 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="TermOfExtensionStudy" xlink:to="ions_TermOfExtensionStudy_lbl" xlink:title="label: TermOfExtensionStudy to ions_TermOfExtensionStudy_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_TermOfExtensionStudy_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_TermOfExtensionStudy_lbl1" xml:lang="en-US" id="ions_TermOfExtensionStudy_lbl1">Term of extension study</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="TermOfExtensionStudy" xlink:to="ions_TermOfExtensionStudy_lbl1" xlink:title="label: TermOfExtensionStudy to ions_TermOfExtensionStudy_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_TermOfExtensionStudy_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_TermOfExtensionStudy_lbl2" xml:lang="en-US" id="ions_TermOfExtensionStudy_lbl2">Term of extension study</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="TermOfExtensionStudy" xlink:to="ions_TermOfExtensionStudy_lbl2" xlink:title="label: TermOfExtensionStudy to ions_TermOfExtensionStudy_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20201231.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-20201231.xsd#ions_MaximumAmountOfPaymentsReceivablePerDrugForSubstantiveMilestonePayments" xlink:label="MaximumAmountOfPaymentsReceivablePerDrugForSubstantiveMilestonePayments" xlink:title="MaximumAmountOfPaymentsReceivablePerDrugForSubstantiveMilestonePayments" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfPaymentsReceivablePerDrugForSubstantiveMilestonePayments_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_MaximumAmountOfPaymentsReceivablePerDrugForSubstantiveMilestonePayments_lbl" xml:lang="en-US" id="ions_MaximumAmountOfPaymentsReceivablePerDrugForSubstantiveMilestonePayments_lbl">The maximum amount of payments receivable per drug for substantive milestone payments under the collaboration agreement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfPaymentsReceivablePerDrugForSubstantiveMilestonePayments" xlink:to="ions_MaximumAmountOfPaymentsReceivablePerDrugForSubstantiveMilestonePayments_lbl" xlink:title="label: MaximumAmountOfPaymentsReceivablePerDrugForSubstantiveMilestonePayments to ions_MaximumAmountOfPaymentsReceivablePerDrugForSubstantiveMilestonePayments_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfPaymentsReceivablePerDrugForSubstantiveMilestonePayments_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_MaximumAmountOfPaymentsReceivablePerDrugForSubstantiveMilestonePayments_lbl1" xml:lang="en-US" id="ions_MaximumAmountOfPaymentsReceivablePerDrugForSubstantiveMilestonePayments_lbl1">Maximum amount of payments receivable per drug for substantive milestone payments</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfPaymentsReceivablePerDrugForSubstantiveMilestonePayments" xlink:to="ions_MaximumAmountOfPaymentsReceivablePerDrugForSubstantiveMilestonePayments_lbl1" xlink:title="label: MaximumAmountOfPaymentsReceivablePerDrugForSubstantiveMilestonePayments to ions_MaximumAmountOfPaymentsReceivablePerDrugForSubstantiveMilestonePayments_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfPaymentsReceivablePerDrugForSubstantiveMilestonePayments_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_MaximumAmountOfPaymentsReceivablePerDrugForSubstantiveMilestonePayments_lbl2" xml:lang="en-US" id="ions_MaximumAmountOfPaymentsReceivablePerDrugForSubstantiveMilestonePayments_lbl2">Maximum amount of payments receivable per drug for substantive milestone payments</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfPaymentsReceivablePerDrugForSubstantiveMilestonePayments" xlink:to="ions_MaximumAmountOfPaymentsReceivablePerDrugForSubstantiveMilestonePayments_lbl2" xlink:title="label: MaximumAmountOfPaymentsReceivablePerDrugForSubstantiveMilestonePayments to ions_MaximumAmountOfPaymentsReceivablePerDrugForSubstantiveMilestonePayments_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20201231.xsd#ions_MedicinesForUndisclosedTargetsMember" xlink:label="MedicinesForUndisclosedTargetsMember" xlink:title="MedicinesForUndisclosedTargetsMember" />
    <link:label xlink:type="resource" xlink:label="ions_MedicinesForUndisclosedTargetsMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_MedicinesForUndisclosedTargetsMember_lbl" xml:lang="en-US" id="ions_MedicinesForUndisclosedTargetsMember_lbl">Medicines to treat undisclosed targets under the collaboration agreement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MedicinesForUndisclosedTargetsMember" xlink:to="ions_MedicinesForUndisclosedTargetsMember_lbl" xlink:title="label: MedicinesForUndisclosedTargetsMember to ions_MedicinesForUndisclosedTargetsMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_MedicinesForUndisclosedTargetsMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_MedicinesForUndisclosedTargetsMember_lbl1" xml:lang="en-US" id="ions_MedicinesForUndisclosedTargetsMember_lbl1">Medicines for Undisclosed Targets [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MedicinesForUndisclosedTargetsMember" xlink:to="ions_MedicinesForUndisclosedTargetsMember_lbl1" xlink:title="label: MedicinesForUndisclosedTargetsMember to ions_MedicinesForUndisclosedTargetsMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_MedicinesForUndisclosedTargetsMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_MedicinesForUndisclosedTargetsMember_lbl2" xml:lang="en-US" id="ions_MedicinesForUndisclosedTargetsMember_lbl2">Medicines for Undisclosed Targets [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MedicinesForUndisclosedTargetsMember" xlink:to="ions_MedicinesForUndisclosedTargetsMember_lbl2" xlink:title="label: MedicinesForUndisclosedTargetsMember to ions_MedicinesForUndisclosedTargetsMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20201231.xsd#ions_Ion464Member" xlink:label="Ion464Member" xlink:title="Ion464Member" />
    <link:label xlink:type="resource" xlink:label="ions_Ion464Member_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_Ion464Member_lbl" xml:lang="en-US" id="ions_Ion464Member_lbl">A medicine to treat patients with multiple system atrophy, formerly known as IONIS-BIIB6.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="Ion464Member" xlink:to="ions_Ion464Member_lbl" xlink:title="label: Ion464Member to ions_Ion464Member_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_Ion464Member_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_Ion464Member_lbl1" xml:lang="en-US" id="ions_Ion464Member_lbl1">ION464 [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="Ion464Member" xlink:to="ions_Ion464Member_lbl1" xlink:title="label: Ion464Member to ions_Ion464Member_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_Ion464Member_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_Ion464Member_lbl2" xml:lang="en-US" id="ions_Ion464Member_lbl2">ION464 [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="Ion464Member" xlink:to="ions_Ion464Member_lbl2" xlink:title="label: Ion464Member to ions_Ion464Member_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20201231.xsd#ions_Ion541Member" xlink:label="Ion541Member" xlink:title="Ion541Member" />
    <link:label xlink:type="resource" xlink:label="ions_Ion541Member_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_Ion541Member_lbl" xml:lang="en-US" id="ions_Ion541Member_lbl">ION541, also known as BIIB105, is an investigational antisense medicine targeting ataxin 2 (ATXN2) RNA.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="Ion541Member" xlink:to="ions_Ion541Member_lbl" xlink:title="label: Ion541Member to ions_Ion541Member_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_Ion541Member_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_Ion541Member_lbl1" xml:lang="en-US" id="ions_Ion541Member_lbl1">Ion541 [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="Ion541Member" xlink:to="ions_Ion541Member_lbl1" xlink:title="label: Ion541Member to ions_Ion541Member_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_Ion541Member_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_Ion541Member_lbl2" xml:lang="en-US" id="ions_Ion541Member_lbl2">ION541 [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="Ion541Member" xlink:to="ions_Ion541Member_lbl2" xlink:title="label: Ion541Member to ions_Ion541Member_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20201231.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-20201231.xsd#ions_NumberOfProgramsBeingAdvanced" xlink:label="NumberOfProgramsBeingAdvanced" xlink:title="NumberOfProgramsBeingAdvanced" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfProgramsBeingAdvanced_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_NumberOfProgramsBeingAdvanced_lbl" xml:lang="en-US" id="ions_NumberOfProgramsBeingAdvanced_lbl">The number of programs 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="NumberOfProgramsBeingAdvanced" xlink:to="ions_NumberOfProgramsBeingAdvanced_lbl" xlink:title="label: NumberOfProgramsBeingAdvanced to ions_NumberOfProgramsBeingAdvanced_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfProgramsBeingAdvanced_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_NumberOfProgramsBeingAdvanced_lbl1" xml:lang="en-US" id="ions_NumberOfProgramsBeingAdvanced_lbl1">Number of programs being advanced</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfProgramsBeingAdvanced" xlink:to="ions_NumberOfProgramsBeingAdvanced_lbl1" xlink:title="label: NumberOfProgramsBeingAdvanced to ions_NumberOfProgramsBeingAdvanced_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfProgramsBeingAdvanced_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_NumberOfProgramsBeingAdvanced_lbl2" xml:lang="en-US" id="ions_NumberOfProgramsBeingAdvanced_lbl2">Number of programs being advanced</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfProgramsBeingAdvanced" xlink:to="ions_NumberOfProgramsBeingAdvanced_lbl2" xlink:title="label: NumberOfProgramsBeingAdvanced to ions_NumberOfProgramsBeingAdvanced_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20201231.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-20201231.xsd#ions_MinimumAmountOfPaymentsReceivableForLicenseFeesAndSubstantiveMilestones" xlink:label="MinimumAmountOfPaymentsReceivableForLicenseFeesAndSubstantiveMilestones" xlink:title="MinimumAmountOfPaymentsReceivableForLicenseFeesAndSubstantiveMilestones" />
    <link:label xlink:type="resource" xlink:label="ions_MinimumAmountOfPaymentsReceivableForLicenseFeesAndSubstantiveMilestones_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_MinimumAmountOfPaymentsReceivableForLicenseFeesAndSubstantiveMilestones_lbl" xml:lang="en-US" id="ions_MinimumAmountOfPaymentsReceivableForLicenseFeesAndSubstantiveMilestones_lbl">The minimum amount of payments receivable for license fees and substantive milestones under the collaboration agreement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MinimumAmountOfPaymentsReceivableForLicenseFeesAndSubstantiveMilestones" xlink:to="ions_MinimumAmountOfPaymentsReceivableForLicenseFeesAndSubstantiveMilestones_lbl" xlink:title="label: MinimumAmountOfPaymentsReceivableForLicenseFeesAndSubstantiveMilestones to ions_MinimumAmountOfPaymentsReceivableForLicenseFeesAndSubstantiveMilestones_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_MinimumAmountOfPaymentsReceivableForLicenseFeesAndSubstantiveMilestones_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_MinimumAmountOfPaymentsReceivableForLicenseFeesAndSubstantiveMilestones_lbl1" xml:lang="en-US" id="ions_MinimumAmountOfPaymentsReceivableForLicenseFeesAndSubstantiveMilestones_lbl1">Minimum amount of payments receivable for license fees and substantive milestones</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MinimumAmountOfPaymentsReceivableForLicenseFeesAndSubstantiveMilestones" xlink:to="ions_MinimumAmountOfPaymentsReceivableForLicenseFeesAndSubstantiveMilestones_lbl1" xlink:title="label: MinimumAmountOfPaymentsReceivableForLicenseFeesAndSubstantiveMilestones to ions_MinimumAmountOfPaymentsReceivableForLicenseFeesAndSubstantiveMilestones_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_MinimumAmountOfPaymentsReceivableForLicenseFeesAndSubstantiveMilestones_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_MinimumAmountOfPaymentsReceivableForLicenseFeesAndSubstantiveMilestones_lbl2" xml:lang="en-US" id="ions_MinimumAmountOfPaymentsReceivableForLicenseFeesAndSubstantiveMilestones_lbl2">Minimum amount of payments receivable for license fees and milestones</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MinimumAmountOfPaymentsReceivableForLicenseFeesAndSubstantiveMilestones" xlink:to="ions_MinimumAmountOfPaymentsReceivableForLicenseFeesAndSubstantiveMilestones_lbl2" xlink:title="label: MinimumAmountOfPaymentsReceivableForLicenseFeesAndSubstantiveMilestones to ions_MinimumAmountOfPaymentsReceivableForLicenseFeesAndSubstantiveMilestones_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20201231.xsd#ions_RevenueFromContractWithCustomerNumberOfNewPerformanceObligations" xlink:label="RevenueFromContractWithCustomerNumberOfNewPerformanceObligations" xlink:title="RevenueFromContractWithCustomerNumberOfNewPerformanceObligations" />
    <link:label xlink:type="resource" xlink:label="ions_RevenueFromContractWithCustomerNumberOfNewPerformanceObligations_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_RevenueFromContractWithCustomerNumberOfNewPerformanceObligations_lbl" xml:lang="en-US" id="ions_RevenueFromContractWithCustomerNumberOfNewPerformanceObligations_lbl">The number of new performance obligations identified under the collaboration agreement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RevenueFromContractWithCustomerNumberOfNewPerformanceObligations" xlink:to="ions_RevenueFromContractWithCustomerNumberOfNewPerformanceObligations_lbl" xlink:title="label: RevenueFromContractWithCustomerNumberOfNewPerformanceObligations to ions_RevenueFromContractWithCustomerNumberOfNewPerformanceObligations_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_RevenueFromContractWithCustomerNumberOfNewPerformanceObligations_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_RevenueFromContractWithCustomerNumberOfNewPerformanceObligations_lbl1" xml:lang="en-US" id="ions_RevenueFromContractWithCustomerNumberOfNewPerformanceObligations_lbl1">Revenue from Contract with Customer, Number of new performance obligations</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RevenueFromContractWithCustomerNumberOfNewPerformanceObligations" xlink:to="ions_RevenueFromContractWithCustomerNumberOfNewPerformanceObligations_lbl1" xlink:title="label: RevenueFromContractWithCustomerNumberOfNewPerformanceObligations to ions_RevenueFromContractWithCustomerNumberOfNewPerformanceObligations_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_RevenueFromContractWithCustomerNumberOfNewPerformanceObligations_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_RevenueFromContractWithCustomerNumberOfNewPerformanceObligations_lbl2" xml:lang="en-US" id="ions_RevenueFromContractWithCustomerNumberOfNewPerformanceObligations_lbl2">Number of new performance obligations</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RevenueFromContractWithCustomerNumberOfNewPerformanceObligations" xlink:to="ions_RevenueFromContractWithCustomerNumberOfNewPerformanceObligations_lbl2" xlink:title="label: RevenueFromContractWithCustomerNumberOfNewPerformanceObligations to ions_RevenueFromContractWithCustomerNumberOfNewPerformanceObligations_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20201231.xsd#ions_RoyaltyPercentageReceivedOnGrossMarginsOfDrugsUnderCollaborationAgreement" xlink:label="RoyaltyPercentageReceivedOnGrossMarginsOfDrugsUnderCollaborationAgreement" xlink:title="RoyaltyPercentageReceivedOnGrossMarginsOfDrugsUnderCollaborationAgreement" />
    <link:label xlink:type="resource" xlink:label="ions_RoyaltyPercentageReceivedOnGrossMarginsOfDrugsUnderCollaborationAgreement_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_RoyaltyPercentageReceivedOnGrossMarginsOfDrugsUnderCollaborationAgreement_lbl" xml:lang="en-US" id="ions_RoyaltyPercentageReceivedOnGrossMarginsOfDrugsUnderCollaborationAgreement_lbl">The royalty percentage received on gross margins of drug(s) under the collaborative arrangement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RoyaltyPercentageReceivedOnGrossMarginsOfDrugsUnderCollaborationAgreement" xlink:to="ions_RoyaltyPercentageReceivedOnGrossMarginsOfDrugsUnderCollaborationAgreement_lbl" xlink:title="label: RoyaltyPercentageReceivedOnGrossMarginsOfDrugsUnderCollaborationAgreement to ions_RoyaltyPercentageReceivedOnGrossMarginsOfDrugsUnderCollaborationAgreement_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_RoyaltyPercentageReceivedOnGrossMarginsOfDrugsUnderCollaborationAgreement_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_RoyaltyPercentageReceivedOnGrossMarginsOfDrugsUnderCollaborationAgreement_lbl1" xml:lang="en-US" id="ions_RoyaltyPercentageReceivedOnGrossMarginsOfDrugsUnderCollaborationAgreement_lbl1">Royalty percentage received on gross margins of drugs under collaboration agreement</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RoyaltyPercentageReceivedOnGrossMarginsOfDrugsUnderCollaborationAgreement" xlink:to="ions_RoyaltyPercentageReceivedOnGrossMarginsOfDrugsUnderCollaborationAgreement_lbl1" xlink:title="label: RoyaltyPercentageReceivedOnGrossMarginsOfDrugsUnderCollaborationAgreement to ions_RoyaltyPercentageReceivedOnGrossMarginsOfDrugsUnderCollaborationAgreement_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_RoyaltyPercentageReceivedOnGrossMarginsOfDrugsUnderCollaborationAgreement_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_RoyaltyPercentageReceivedOnGrossMarginsOfDrugsUnderCollaborationAgreement_lbl2" xml:lang="en-US" id="ions_RoyaltyPercentageReceivedOnGrossMarginsOfDrugsUnderCollaborationAgreement_lbl2">Royalty percentage received on gross margins of both drugs combined</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RoyaltyPercentageReceivedOnGrossMarginsOfDrugsUnderCollaborationAgreement" xlink:to="ions_RoyaltyPercentageReceivedOnGrossMarginsOfDrugsUnderCollaborationAgreement_lbl2" xlink:title="label: RoyaltyPercentageReceivedOnGrossMarginsOfDrugsUnderCollaborationAgreement to ions_RoyaltyPercentageReceivedOnGrossMarginsOfDrugsUnderCollaborationAgreement_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20201231.xsd#ions_ResearchAndDevelopmentServicesForIonisFxiLMember" xlink:label="ResearchAndDevelopmentServicesForIonisFxiLMember" xlink:title="ResearchAndDevelopmentServicesForIonisFxiLMember" />
    <link:label xlink:type="resource" xlink:label="ions_ResearchAndDevelopmentServicesForIonisFxiLMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_ResearchAndDevelopmentServicesForIonisFxiLMember_lbl" xml:lang="en-US" id="ions_ResearchAndDevelopmentServicesForIonisFxiLMember_lbl">Research and development (R&amp;D) services for IONIS-FXI-L, a ligand-conjugated (LICA) investigational antisense medicine designed to reduce the production of Factor XI, a clotting factor produced in the liver that is an important component of the coagulation pathway.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ResearchAndDevelopmentServicesForIonisFxiLMember" xlink:to="ions_ResearchAndDevelopmentServicesForIonisFxiLMember_lbl" xlink:title="label: ResearchAndDevelopmentServicesForIonisFxiLMember to ions_ResearchAndDevelopmentServicesForIonisFxiLMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_ResearchAndDevelopmentServicesForIonisFxiLMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_ResearchAndDevelopmentServicesForIonisFxiLMember_lbl1" xml:lang="en-US" id="ions_ResearchAndDevelopmentServicesForIonisFxiLMember_lbl1">Research and Development Services for Ionis-Fxi-L [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ResearchAndDevelopmentServicesForIonisFxiLMember" xlink:to="ions_ResearchAndDevelopmentServicesForIonisFxiLMember_lbl1" xlink:title="label: ResearchAndDevelopmentServicesForIonisFxiLMember to ions_ResearchAndDevelopmentServicesForIonisFxiLMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_ResearchAndDevelopmentServicesForIonisFxiLMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_ResearchAndDevelopmentServicesForIonisFxiLMember_lbl2" xml:lang="en-US" id="ions_ResearchAndDevelopmentServicesForIonisFxiLMember_lbl2">R&amp;D Services for IONIS-FXI-L [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ResearchAndDevelopmentServicesForIonisFxiLMember" xlink:to="ions_ResearchAndDevelopmentServicesForIonisFxiLMember_lbl2" xlink:title="label: ResearchAndDevelopmentServicesForIonisFxiLMember to ions_ResearchAndDevelopmentServicesForIonisFxiLMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20201231.xsd#ions_IonisFxiLMember" xlink:label="IonisFxiLMember" xlink:title="IonisFxiLMember" />
    <link:label xlink:type="resource" xlink:label="ions_IonisFxiLMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_IonisFxiLMember_lbl" xml:lang="en-US" id="ions_IonisFxiLMember_lbl">IONIS-FXI-LRx is a ligand-conjugated (LICA) investigational antisense medicine designed to reduce the production of Factor XI, a clotting factor produced in the liver that is an important component of the coagulation pathway.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IonisFxiLMember" xlink:to="ions_IonisFxiLMember_lbl" xlink:title="label: IonisFxiLMember to ions_IonisFxiLMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_IonisFxiLMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_IonisFxiLMember_lbl1" xml:lang="en-US" id="ions_IonisFxiLMember_lbl1">Ionis-Fxi-L [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IonisFxiLMember" xlink:to="ions_IonisFxiLMember_lbl1" xlink:title="label: IonisFxiLMember to ions_IonisFxiLMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_IonisFxiLMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_IonisFxiLMember_lbl2" xml:lang="en-US" id="ions_IonisFxiLMember_lbl2">IONIS-FXI-L [Member]</link:label>
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    <link:loc xlink:type="locator" xlink:href="ions-20201231.xsd#ions_CollaborativeArrangementAndLicensingAgreementAmendedInFebruary2017WithBayerMember" xlink:label="CollaborativeArrangementAndLicensingAgreementAmendedInFebruary2017WithBayerMember" xlink:title="CollaborativeArrangementAndLicensingAgreementAmendedInFebruary2017WithBayerMember" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementAndLicensingAgreementAmendedInFebruary2017WithBayerMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_CollaborativeArrangementAndLicensingAgreementAmendedInFebruary2017WithBayerMember_lbl" xml:lang="en-US" id="ions_CollaborativeArrangementAndLicensingAgreementAmendedInFebruary2017WithBayerMember_lbl">Represents information pertaining to collaborative arrangement with Bayer HealthCare amended in February 2017 to advance IONIS-FXIRx for the prevention of thrombosis and to initiate development of IONIS-FXI-LRx.</link:label>
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementAndLicensingAgreementAmendedInFebruary2017WithBayerMember" xlink:to="ions_CollaborativeArrangementAndLicensingAgreementAmendedInFebruary2017WithBayerMember_lbl1" xlink:title="label: CollaborativeArrangementAndLicensingAgreementAmendedInFebruary2017WithBayerMember to ions_CollaborativeArrangementAndLicensingAgreementAmendedInFebruary2017WithBayerMember_lbl1" />
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementAndLicensingAgreementAmendedInFebruary2017WithBayerMember" xlink:to="ions_CollaborativeArrangementAndLicensingAgreementAmendedInFebruary2017WithBayerMember_lbl2" xlink:title="label: CollaborativeArrangementAndLicensingAgreementAmendedInFebruary2017WithBayerMember to ions_CollaborativeArrangementAndLicensingAgreementAmendedInFebruary2017WithBayerMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20201231.xsd#ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMay2015WithBayerMember" xlink:label="CollaborativeArrangementAndLicensingAgreementEnteredIntoInMay2015WithBayerMember" xlink:title="CollaborativeArrangementAndLicensingAgreementEnteredIntoInMay2015WithBayerMember" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMay2015WithBayerMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMay2015WithBayerMember_lbl" xml:lang="en-US" id="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMay2015WithBayerMember_lbl">Represents information pertaining to collaborative arrangement entered into with Bayer HealthCare in May 2015 to develop and commercialize IONIS-FXI for the prevention of thrombosis.</link:label>
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    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMay2015WithBayerMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMay2015WithBayerMember_lbl2" xml:lang="en-US" id="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMay2015WithBayerMember_lbl2">Bayer [Member]</link:label>
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    <link:loc xlink:type="locator" xlink:href="ions-20201231.xsd#ions_PaymentReceivedForAdvancingPrograms" xlink:label="PaymentReceivedForAdvancingPrograms" xlink:title="PaymentReceivedForAdvancingPrograms" />
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    <link:label xlink:type="resource" xlink:label="ions_PaymentReceivedForAdvancingPrograms_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_PaymentReceivedForAdvancingPrograms_lbl1" xml:lang="en-US" id="ions_PaymentReceivedForAdvancingPrograms_lbl1">Payment received for advancing programs</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PaymentReceivedForAdvancingPrograms" xlink:to="ions_PaymentReceivedForAdvancingPrograms_lbl1" xlink:title="label: PaymentReceivedForAdvancingPrograms to ions_PaymentReceivedForAdvancingPrograms_lbl1" />
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PaymentReceivedForAdvancingPrograms" xlink:to="ions_PaymentReceivedForAdvancingPrograms_lbl2" xlink:title="label: PaymentReceivedForAdvancingPrograms to ions_PaymentReceivedForAdvancingPrograms_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20201231.xsd#ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember" xlink:label="CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember" xlink:title="CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember_lbl" xml:lang="en-US" id="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember_lbl">Represents information pertaining to the collaborative arrangement 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="CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember" xlink:to="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember_lbl" xlink:title="label: CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember to ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember_lbl1" xml:lang="en-US" id="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember_lbl1">Collaborative Arrangement and Licensing Agreement Entered Into in April 2013 with Roche [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember" xlink:to="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember_lbl1" xlink:title="label: CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember to ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember_lbl2" xml:lang="en-US" id="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember_lbl2">Huntington's Disease [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember" xlink:to="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember_lbl2" xlink:title="label: CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember to ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20201231.xsd#ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember" xlink:label="CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember" xlink:title="CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember_lbl" xml:lang="en-US" id="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember_lbl">Represents information pertaining to the collaborative arrangement entered into with Hoffman-La Roche Inc. and F. Hoffmann-La Roche Ltd., collectively Roche, in October 2018 to develop IONIS-FB-LRx 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="CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember" xlink:to="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember_lbl" xlink:title="label: CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember to ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember_lbl1" xml:lang="en-US" id="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember_lbl1">Collaborative Arrangement and Licensing Agreement Entered Into in October 2018 with Roche [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember" xlink:to="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember_lbl1" xlink:title="label: CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember to ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember_lbl2" xml:lang="en-US" id="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember_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="CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember" xlink:to="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember_lbl2" xlink:title="label: CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember to ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember_lbl2" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember_lbl3" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember_lbl3" xml:lang="en-US" id="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember_lbl3">Roche 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="CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember" xlink:to="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember_lbl3" xlink:title="label: CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember to ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember_lbl3" />
    <link:loc xlink:type="locator" xlink:href="ions-20201231.xsd#ions_MilestonePaymentsReceived" xlink:label="MilestonePaymentsReceived" xlink:title="MilestonePaymentsReceived" />
    <link:label xlink:type="resource" xlink:label="ions_MilestonePaymentsReceived_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_MilestonePaymentsReceived_lbl" xml:lang="en-US" id="ions_MilestonePaymentsReceived_lbl">The amount of milestone 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="MilestonePaymentsReceived" xlink:to="ions_MilestonePaymentsReceived_lbl" xlink:title="label: MilestonePaymentsReceived to ions_MilestonePaymentsReceived_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_MilestonePaymentsReceived_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_MilestonePaymentsReceived_lbl1" xml:lang="en-US" id="ions_MilestonePaymentsReceived_lbl1">Milestone payments received</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MilestonePaymentsReceived" xlink:to="ions_MilestonePaymentsReceived_lbl1" xlink:title="label: MilestonePaymentsReceived to ions_MilestonePaymentsReceived_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_MilestonePaymentsReceived_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_MilestonePaymentsReceived_lbl2" xml:lang="en-US" id="ions_MilestonePaymentsReceived_lbl2">Milestone payment received</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MilestonePaymentsReceived" xlink:to="ions_MilestonePaymentsReceived_lbl2" xlink:title="label: MilestonePaymentsReceived to ions_MilestonePaymentsReceived_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20201231.xsd#ions_MaximumAmountOfPaymentsReceivableForLicenseFeesAndMilestones" xlink:label="MaximumAmountOfPaymentsReceivableForLicenseFeesAndMilestones" xlink:title="MaximumAmountOfPaymentsReceivableForLicenseFeesAndMilestones" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfPaymentsReceivableForLicenseFeesAndMilestones_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_MaximumAmountOfPaymentsReceivableForLicenseFeesAndMilestones_lbl" xml:lang="en-US" id="ions_MaximumAmountOfPaymentsReceivableForLicenseFeesAndMilestones_lbl">Maximum amount of payments receivable for license fees and milestone payments under the collaboration agreement.</link:label>
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    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfPaymentsReceivableForLicenseFeesAndMilestones_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_MaximumAmountOfPaymentsReceivableForLicenseFeesAndMilestones_lbl1" xml:lang="en-US" id="ions_MaximumAmountOfPaymentsReceivableForLicenseFeesAndMilestones_lbl1">Maximum amount of payments receivable for license fees and milestones</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfPaymentsReceivableForLicenseFeesAndMilestones" xlink:to="ions_MaximumAmountOfPaymentsReceivableForLicenseFeesAndMilestones_lbl1" xlink:title="label: MaximumAmountOfPaymentsReceivableForLicenseFeesAndMilestones to ions_MaximumAmountOfPaymentsReceivableForLicenseFeesAndMilestones_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfPaymentsReceivableForLicenseFeesAndMilestones_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_MaximumAmountOfPaymentsReceivableForLicenseFeesAndMilestones_lbl2" xml:lang="en-US" id="ions_MaximumAmountOfPaymentsReceivableForLicenseFeesAndMilestones_lbl2">Maximum amount of payments receivable for license fees and milestones</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfPaymentsReceivableForLicenseFeesAndMilestones" xlink:to="ions_MaximumAmountOfPaymentsReceivableForLicenseFeesAndMilestones_lbl2" xlink:title="label: MaximumAmountOfPaymentsReceivableForLicenseFeesAndMilestones to ions_MaximumAmountOfPaymentsReceivableForLicenseFeesAndMilestones_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20201231.xsd#ions_MaximumAmountOfPaymentReceivableForEachAdditionalDrugDeveloped" xlink:label="MaximumAmountOfPaymentReceivableForEachAdditionalDrugDeveloped" xlink:title="MaximumAmountOfPaymentReceivableForEachAdditionalDrugDeveloped" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfPaymentReceivableForEachAdditionalDrugDeveloped_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_MaximumAmountOfPaymentReceivableForEachAdditionalDrugDeveloped_lbl" xml:lang="en-US" id="ions_MaximumAmountOfPaymentReceivableForEachAdditionalDrugDeveloped_lbl">The maximum amount of payments receivable for each additional drug developed under the collaboration agreement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfPaymentReceivableForEachAdditionalDrugDeveloped" xlink:to="ions_MaximumAmountOfPaymentReceivableForEachAdditionalDrugDeveloped_lbl" xlink:title="label: MaximumAmountOfPaymentReceivableForEachAdditionalDrugDeveloped to ions_MaximumAmountOfPaymentReceivableForEachAdditionalDrugDeveloped_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfPaymentReceivableForEachAdditionalDrugDeveloped_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_MaximumAmountOfPaymentReceivableForEachAdditionalDrugDeveloped_lbl1" xml:lang="en-US" id="ions_MaximumAmountOfPaymentReceivableForEachAdditionalDrugDeveloped_lbl1">Maximum amount of payment receivable for each additional drug developed</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfPaymentReceivableForEachAdditionalDrugDeveloped" xlink:to="ions_MaximumAmountOfPaymentReceivableForEachAdditionalDrugDeveloped_lbl1" xlink:title="label: MaximumAmountOfPaymentReceivableForEachAdditionalDrugDeveloped to ions_MaximumAmountOfPaymentReceivableForEachAdditionalDrugDeveloped_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfPaymentReceivableForEachAdditionalDrugDeveloped_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_MaximumAmountOfPaymentReceivableForEachAdditionalDrugDeveloped_lbl2" xml:lang="en-US" id="ions_MaximumAmountOfPaymentReceivableForEachAdditionalDrugDeveloped_lbl2">Maximum amount of payment receivable for each additional drug developed</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfPaymentReceivableForEachAdditionalDrugDeveloped" xlink:to="ions_MaximumAmountOfPaymentReceivableForEachAdditionalDrugDeveloped_lbl2" xlink:title="label: MaximumAmountOfPaymentReceivableForEachAdditionalDrugDeveloped to ions_MaximumAmountOfPaymentReceivableForEachAdditionalDrugDeveloped_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20201231.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 (IgA) nephropathy 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">IgA 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_lbl2" xlink:title="label: ImmunoglobulinANephropathyMember to ions_ImmunoglobulinANephropathyMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20201231.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-20201231.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-20201231.xsd#ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInAugust2018WithPtcTherapeuticsMember" xlink:label="CollaborativeArrangementAndLicensingAgreementEnteredIntoInAugust2018WithPtcTherapeuticsMember" xlink:title="CollaborativeArrangementAndLicensingAgreementEnteredIntoInAugust2018WithPtcTherapeuticsMember" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInAugust2018WithPtcTherapeuticsMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInAugust2018WithPtcTherapeuticsMember_lbl" xml:lang="en-US" id="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInAugust2018WithPtcTherapeuticsMember_lbl">Represents information pertaining to the collaborative arrangement entered into with PTC Therapeutics in August 2018 to commercialize TEGSEDI and WAYLIVRA in Latin America.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementAndLicensingAgreementEnteredIntoInAugust2018WithPtcTherapeuticsMember" xlink:to="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInAugust2018WithPtcTherapeuticsMember_lbl" xlink:title="label: CollaborativeArrangementAndLicensingAgreementEnteredIntoInAugust2018WithPtcTherapeuticsMember to ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInAugust2018WithPtcTherapeuticsMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInAugust2018WithPtcTherapeuticsMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInAugust2018WithPtcTherapeuticsMember_lbl1" xml:lang="en-US" id="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInAugust2018WithPtcTherapeuticsMember_lbl1">Collaborative Arrangement and Licensing Agreement Entered Into in August 2018 with PTC Therapeutics [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementAndLicensingAgreementEnteredIntoInAugust2018WithPtcTherapeuticsMember" xlink:to="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInAugust2018WithPtcTherapeuticsMember_lbl1" xlink:title="label: CollaborativeArrangementAndLicensingAgreementEnteredIntoInAugust2018WithPtcTherapeuticsMember to ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInAugust2018WithPtcTherapeuticsMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInAugust2018WithPtcTherapeuticsMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInAugust2018WithPtcTherapeuticsMember_lbl2" xml:lang="en-US" id="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInAugust2018WithPtcTherapeuticsMember_lbl2">PTC Therapeutics [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementAndLicensingAgreementEnteredIntoInAugust2018WithPtcTherapeuticsMember" xlink:to="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInAugust2018WithPtcTherapeuticsMember_lbl2" xlink:title="label: CollaborativeArrangementAndLicensingAgreementEnteredIntoInAugust2018WithPtcTherapeuticsMember to ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInAugust2018WithPtcTherapeuticsMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20201231.xsd#ions_CollaborativeArrangementsAndLicensingAgreementsAstrazenecaMember" xlink:label="CollaborativeArrangementsAndLicensingAgreementsAstrazenecaMember" xlink:title="CollaborativeArrangementsAndLicensingAgreementsAstrazenecaMember" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementsAndLicensingAgreementsAstrazenecaMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_CollaborativeArrangementsAndLicensingAgreementsAstrazenecaMember_lbl" xml:lang="en-US" id="ions_CollaborativeArrangementsAndLicensingAgreementsAstrazenecaMember_lbl">Represents information pertaining to the collaborative arrangements and licensing 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="CollaborativeArrangementsAndLicensingAgreementsAstrazenecaMember" xlink:to="ions_CollaborativeArrangementsAndLicensingAgreementsAstrazenecaMember_lbl" xlink:title="label: CollaborativeArrangementsAndLicensingAgreementsAstrazenecaMember to ions_CollaborativeArrangementsAndLicensingAgreementsAstrazenecaMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementsAndLicensingAgreementsAstrazenecaMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_CollaborativeArrangementsAndLicensingAgreementsAstrazenecaMember_lbl1" xml:lang="en-US" id="ions_CollaborativeArrangementsAndLicensingAgreementsAstrazenecaMember_lbl1">Collaborative Arrangements and Licensing Agreements, AstraZeneca [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementsAndLicensingAgreementsAstrazenecaMember" xlink:to="ions_CollaborativeArrangementsAndLicensingAgreementsAstrazenecaMember_lbl1" xlink:title="label: CollaborativeArrangementsAndLicensingAgreementsAstrazenecaMember to ions_CollaborativeArrangementsAndLicensingAgreementsAstrazenecaMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementsAndLicensingAgreementsAstrazenecaMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_CollaborativeArrangementsAndLicensingAgreementsAstrazenecaMember_lbl2" xml:lang="en-US" id="ions_CollaborativeArrangementsAndLicensingAgreementsAstrazenecaMember_lbl2">AstraZeneca [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementsAndLicensingAgreementsAstrazenecaMember" xlink:to="ions_CollaborativeArrangementsAndLicensingAgreementsAstrazenecaMember_lbl2" xlink:title="label: CollaborativeArrangementsAndLicensingAgreementsAstrazenecaMember to ions_CollaborativeArrangementsAndLicensingAgreementsAstrazenecaMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20201231.xsd#ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2014WithJanssenBiotechIncMember" xlink:label="CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2014WithJanssenBiotechIncMember" xlink:title="CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2014WithJanssenBiotechIncMember" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2014WithJanssenBiotechIncMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2014WithJanssenBiotechIncMember_lbl" xml:lang="en-US" id="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2014WithJanssenBiotechIncMember_lbl">Represents information pertaining to the collaborative arrangement entered into with Janssen Biotech, Inc. in December 2014 to discover and develop antisense drugs that can be locally administered, including oral delivery, to treat autoimmune disorders of the gastrointestinal tract.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2014WithJanssenBiotechIncMember" xlink:to="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2014WithJanssenBiotechIncMember_lbl" xlink:title="label: CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2014WithJanssenBiotechIncMember to ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2014WithJanssenBiotechIncMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2014WithJanssenBiotechIncMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2014WithJanssenBiotechIncMember_lbl1" xml:lang="en-US" id="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2014WithJanssenBiotechIncMember_lbl1">Collaborative Arrangement and Licensing Agreement Entered Into in December 2014 with Janssen Biotech, Inc. [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2014WithJanssenBiotechIncMember" xlink:to="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2014WithJanssenBiotechIncMember_lbl1" xlink:title="label: CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2014WithJanssenBiotechIncMember to ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2014WithJanssenBiotechIncMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2014WithJanssenBiotechIncMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2014WithJanssenBiotechIncMember_lbl2" xml:lang="en-US" id="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2014WithJanssenBiotechIncMember_lbl2">Janssen Biotech, Inc. [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2014WithJanssenBiotechIncMember" xlink:to="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2014WithJanssenBiotechIncMember_lbl2" xlink:title="label: CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2014WithJanssenBiotechIncMember to ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2014WithJanssenBiotechIncMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20201231.xsd#ions_CollaborativeArrangementsAndLicensingAgreementsBiogenMember" xlink:label="CollaborativeArrangementsAndLicensingAgreementsBiogenMember" xlink:title="CollaborativeArrangementsAndLicensingAgreementsBiogenMember" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementsAndLicensingAgreementsBiogenMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_CollaborativeArrangementsAndLicensingAgreementsBiogenMember_lbl" xml:lang="en-US" id="ions_CollaborativeArrangementsAndLicensingAgreementsBiogenMember_lbl">Represents information pertaining to the collaborative arrangements and licensing 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="CollaborativeArrangementsAndLicensingAgreementsBiogenMember" xlink:to="ions_CollaborativeArrangementsAndLicensingAgreementsBiogenMember_lbl" xlink:title="label: CollaborativeArrangementsAndLicensingAgreementsBiogenMember to ions_CollaborativeArrangementsAndLicensingAgreementsBiogenMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementsAndLicensingAgreementsBiogenMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_CollaborativeArrangementsAndLicensingAgreementsBiogenMember_lbl1" xml:lang="en-US" id="ions_CollaborativeArrangementsAndLicensingAgreementsBiogenMember_lbl1">Collaborative Arrangements and Licensing Agreements, Biogen [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementsAndLicensingAgreementsBiogenMember" xlink:to="ions_CollaborativeArrangementsAndLicensingAgreementsBiogenMember_lbl1" xlink:title="label: CollaborativeArrangementsAndLicensingAgreementsBiogenMember to ions_CollaborativeArrangementsAndLicensingAgreementsBiogenMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementsAndLicensingAgreementsBiogenMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_CollaborativeArrangementsAndLicensingAgreementsBiogenMember_lbl2" xml:lang="en-US" id="ions_CollaborativeArrangementsAndLicensingAgreementsBiogenMember_lbl2">Biogen [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementsAndLicensingAgreementsBiogenMember" xlink:to="ions_CollaborativeArrangementsAndLicensingAgreementsBiogenMember_lbl2" xlink:title="label: CollaborativeArrangementsAndLicensingAgreementsBiogenMember to ions_CollaborativeArrangementsAndLicensingAgreementsBiogenMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20201231.xsd#ions_CollaborativeArrangementsAndLicensingAgreementsBayerMember" xlink:label="CollaborativeArrangementsAndLicensingAgreementsBayerMember" xlink:title="CollaborativeArrangementsAndLicensingAgreementsBayerMember" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementsAndLicensingAgreementsBayerMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_CollaborativeArrangementsAndLicensingAgreementsBayerMember_lbl" xml:lang="en-US" id="ions_CollaborativeArrangementsAndLicensingAgreementsBayerMember_lbl">Represents information pertaining to the collaborative arrangements and licensing agreements entered into with Bayer HealthCare.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementsAndLicensingAgreementsBayerMember" xlink:to="ions_CollaborativeArrangementsAndLicensingAgreementsBayerMember_lbl" xlink:title="label: CollaborativeArrangementsAndLicensingAgreementsBayerMember to ions_CollaborativeArrangementsAndLicensingAgreementsBayerMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementsAndLicensingAgreementsBayerMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_CollaborativeArrangementsAndLicensingAgreementsBayerMember_lbl1" xml:lang="en-US" id="ions_CollaborativeArrangementsAndLicensingAgreementsBayerMember_lbl1">Collaborative Arrangements and Licensing Agreements, Bayer [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementsAndLicensingAgreementsBayerMember" xlink:to="ions_CollaborativeArrangementsAndLicensingAgreementsBayerMember_lbl1" xlink:title="label: CollaborativeArrangementsAndLicensingAgreementsBayerMember to ions_CollaborativeArrangementsAndLicensingAgreementsBayerMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementsAndLicensingAgreementsBayerMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_CollaborativeArrangementsAndLicensingAgreementsBayerMember_lbl2" xml:lang="en-US" id="ions_CollaborativeArrangementsAndLicensingAgreementsBayerMember_lbl2">Bayer [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementsAndLicensingAgreementsBayerMember" xlink:to="ions_CollaborativeArrangementsAndLicensingAgreementsBayerMember_lbl2" xlink:title="label: CollaborativeArrangementsAndLicensingAgreementsBayerMember to ions_CollaborativeArrangementsAndLicensingAgreementsBayerMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20201231.xsd#ions_CollaborativeArrangementsAndLicensingAgreementsRocheMember" xlink:label="CollaborativeArrangementsAndLicensingAgreementsRocheMember" xlink:title="CollaborativeArrangementsAndLicensingAgreementsRocheMember" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementsAndLicensingAgreementsRocheMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_CollaborativeArrangementsAndLicensingAgreementsRocheMember_lbl" xml:lang="en-US" id="ions_CollaborativeArrangementsAndLicensingAgreementsRocheMember_lbl">Represents information pertaining to the collaborative arrangements and licensing 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="CollaborativeArrangementsAndLicensingAgreementsRocheMember" xlink:to="ions_CollaborativeArrangementsAndLicensingAgreementsRocheMember_lbl" xlink:title="label: CollaborativeArrangementsAndLicensingAgreementsRocheMember to ions_CollaborativeArrangementsAndLicensingAgreementsRocheMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementsAndLicensingAgreementsRocheMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_CollaborativeArrangementsAndLicensingAgreementsRocheMember_lbl1" xml:lang="en-US" id="ions_CollaborativeArrangementsAndLicensingAgreementsRocheMember_lbl1">Collaborative Arrangements and Licensing Agreements, Roche [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementsAndLicensingAgreementsRocheMember" xlink:to="ions_CollaborativeArrangementsAndLicensingAgreementsRocheMember_lbl1" xlink:title="label: CollaborativeArrangementsAndLicensingAgreementsRocheMember to ions_CollaborativeArrangementsAndLicensingAgreementsRocheMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementsAndLicensingAgreementsRocheMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_CollaborativeArrangementsAndLicensingAgreementsRocheMember_lbl2" xml:lang="en-US" id="ions_CollaborativeArrangementsAndLicensingAgreementsRocheMember_lbl2">Roche [Member]</link:label>
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    <link:loc xlink:type="locator" xlink:href="ions-20201231.xsd#ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGlaxoSmithKlineMember" xlink:label="CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGlaxoSmithKlineMember" xlink:title="CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGlaxoSmithKlineMember" />
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    <link:loc xlink:type="locator" xlink:href="ions-20201231.xsd#ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember" xlink:label="CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember" xlink:title="CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember_lbl" xml:lang="en-US" id="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember_lbl">Represents information pertaining to the collaborative arrangements and licensing agreements entered into with Novartis to develop and commercialize AKCEA-APO(a)-L and AKCEA-APOCIII-L.</link:label>
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    <link:loc xlink:type="locator" xlink:href="ions-20201231.xsd#ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems" xlink:label="CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems" xlink:title="CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems" />
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    <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-20201231.xsd#ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureTable" xlink:label="CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureTable" xlink:title="CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureTable" />
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    <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>
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    <link:loc xlink:type="locator" xlink:href="ions-20201231.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:loc xlink:type="locator" xlink:href="ions-20201231.xsd#ions_AccruedInLicensingFeesCurrent" xlink:label="AccruedInLicensingFeesCurrent" xlink:title="AccruedInLicensingFeesCurrent" />
    <link:label xlink:type="resource" xlink:label="ions_AccruedInLicensingFeesCurrent_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_AccruedInLicensingFeesCurrent_lbl" xml:lang="en-US" id="ions_AccruedInLicensingFeesCurrent_lbl">Carrying value as of the balance sheet date of obligations incurred through that date and payable for in-licensing fees under collaboration agreements. Used to reflect the current portion of the liabilities (due within one year or within the normal operating cycle if longer).</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AccruedInLicensingFeesCurrent" xlink:to="ions_AccruedInLicensingFeesCurrent_lbl" xlink:title="label: AccruedInLicensingFeesCurrent to ions_AccruedInLicensingFeesCurrent_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_AccruedInLicensingFeesCurrent_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_AccruedInLicensingFeesCurrent_lbl1" xml:lang="en-US" id="ions_AccruedInLicensingFeesCurrent_lbl1">Accrued in-licensing fees, Current</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AccruedInLicensingFeesCurrent" xlink:to="ions_AccruedInLicensingFeesCurrent_lbl1" xlink:title="label: AccruedInLicensingFeesCurrent to ions_AccruedInLicensingFeesCurrent_lbl1" />
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AccruedInLicensingFeesCurrent" xlink:to="ions_AccruedInLicensingFeesCurrent_lbl2" xlink:title="label: AccruedInLicensingFeesCurrent to ions_AccruedInLicensingFeesCurrent_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20201231.xsd#ions_AccruedClinicalExpenses" xlink:label="AccruedClinicalExpenses" xlink:title="AccruedClinicalExpenses" />
    <link:label xlink:type="resource" xlink:label="ions_AccruedClinicalExpenses_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_AccruedClinicalExpenses_lbl" xml:lang="en-US" id="ions_AccruedClinicalExpenses_lbl">Carrying value as of the balance sheet date of obligations incurred through that date and payable for clinical expenses. Used to reflect the current portion of the liabilities (due within one year or within the normal operating cycle if longer).</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AccruedClinicalExpenses" xlink:to="ions_AccruedClinicalExpenses_lbl" xlink:title="label: AccruedClinicalExpenses to ions_AccruedClinicalExpenses_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_AccruedClinicalExpenses_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_AccruedClinicalExpenses_lbl1" xml:lang="en-US" id="ions_AccruedClinicalExpenses_lbl1">Accrued clinical expenses</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AccruedClinicalExpenses" xlink:to="ions_AccruedClinicalExpenses_lbl1" xlink:title="label: AccruedClinicalExpenses to ions_AccruedClinicalExpenses_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_AccruedClinicalExpenses_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_AccruedClinicalExpenses_lbl2" xml:lang="en-US" id="ions_AccruedClinicalExpenses_lbl2">Clincial expenses</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AccruedClinicalExpenses" xlink:to="ions_AccruedClinicalExpenses_lbl2" xlink:title="label: AccruedClinicalExpenses to ions_AccruedClinicalExpenses_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20201231.xsd#ions_AccruedCommercialExpensesCurrent" xlink:label="AccruedCommercialExpensesCurrent" xlink:title="AccruedCommercialExpensesCurrent" />
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    <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" />
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    <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-20201231.xsd#ions_SignificantPartnersMember" xlink:label="SignificantPartnersMember" xlink:title="SignificantPartnersMember" />
    <link:label xlink:type="resource" xlink:label="ions_SignificantPartnersMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_SignificantPartnersMember_lbl" xml:lang="en-US" id="ions_SignificantPartnersMember_lbl">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="SignificantPartnersMember" xlink:to="ions_SignificantPartnersMember_lbl" xlink:title="label: SignificantPartnersMember to ions_SignificantPartnersMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_SignificantPartnersMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_SignificantPartnersMember_lbl1" xml:lang="en-US" id="ions_SignificantPartnersMember_lbl1">Significant Partners [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SignificantPartnersMember" xlink:to="ions_SignificantPartnersMember_lbl1" xlink:title="label: SignificantPartnersMember to ions_SignificantPartnersMember_lbl1" />
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SignificantPartnersMember" xlink:to="ions_SignificantPartnersMember_lbl2" xlink:title="label: SignificantPartnersMember to ions_SignificantPartnersMember_lbl2" />
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    <link:label xlink:type="resource" xlink:label="ions_NumberOfSignificantPartners_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_NumberOfSignificantPartners_lbl" xml:lang="en-US" id="ions_NumberOfSignificantPartners_lbl">Represents the number of significant partners.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfSignificantPartners" xlink:to="ions_NumberOfSignificantPartners_lbl" xlink:title="label: NumberOfSignificantPartners to ions_NumberOfSignificantPartners_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfSignificantPartners_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_NumberOfSignificantPartners_lbl1" xml:lang="en-US" id="ions_NumberOfSignificantPartners_lbl1">Number of Significant Partners</link:label>
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    <link:loc xlink:type="locator" xlink:href="ions-20201231.xsd#ions_NumberOfInvestmentsInPrivatelyHeldCompaniesThatWereRevalued" xlink:label="NumberOfInvestmentsInPrivatelyHeldCompaniesThatWereRevalued" xlink:title="NumberOfInvestmentsInPrivatelyHeldCompaniesThatWereRevalued" />
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    <link:loc xlink:type="locator" xlink:href="ions-20201231.xsd#ions_AroBiotherapeuticsMember" xlink:label="AroBiotherapeuticsMember" xlink:title="AroBiotherapeuticsMember" />
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    <link:loc xlink:type="locator" xlink:href="ions-20201231.xsd#ions_DynacureSasMember" xlink:label="DynacureSasMember" xlink:title="DynacureSasMember" />
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    <link:loc xlink:type="locator" xlink:href="ions-20201231.xsd#ions_SuzhouRiboLifeScienceCoLtdMember" xlink:label="SuzhouRiboLifeScienceCoLtdMember" xlink:title="SuzhouRiboLifeScienceCoLtdMember" />
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    <link:loc xlink:type="locator" xlink:href="ions-20201231.xsd#ions_AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage" xlink:label="AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage" xlink:title="AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage" />
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    <link:loc xlink:type="locator" xlink:href="ions-20201231.xsd#ions_NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment" xlink:label="NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment" xlink:title="NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment" />
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    <link:label xlink:type="resource" xlink:label="ions_NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment_lbl2" xml:lang="en-US" id="ions_NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment_lbl2">Number of privately held companies in which there is an equity ownership interest of less than 20%</link:label>
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    <link:loc xlink:type="locator" xlink:href="ions-20201231.xsd#ions_AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage" xlink:label="AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage" xlink:title="AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage" />
    <link:label xlink:type="resource" xlink:label="ions_AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage_lbl" xml:lang="en-US" id="ions_AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage_lbl">The percentage of available-for-sale debt securities that mature within two years of the balance sheet date.</link:label>
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    <link:label xlink:type="resource" xlink:label="ions_AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage_lbl1" xml:lang="en-US" id="ions_AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage_lbl1">Available-for-sale Securities, Debt Maturities, within Two Years, Percentage</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage" xlink:to="ions_AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage_lbl1" xlink:title="label: AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage to ions_AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage_lbl2" xml:lang="en-US" id="ions_AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage_lbl2">Percentage of available-for-sale securities with a maturity of less than two years</link:label>
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    <link:loc xlink:type="locator" xlink:href="ions-20201231.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>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeAndOneHalfYearsPercentage" xlink:to="ions_AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeAndOneHalfYearsPercentage_lbl1" xlink:title="label: AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeAndOneHalfYearsPercentage to ions_AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeAndOneHalfYearsPercentage_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeAndOneHalfYearsPercentage_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeAndOneHalfYearsPercentage_lbl2" xml:lang="en-US" id="ions_AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeAndOneHalfYearsPercentage_lbl2">After two years but within three and a half years</link:label>
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    <link:loc xlink:type="locator" xlink:href="ions-20201231.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-20201231.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-20201231.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>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumContractMaturityPeriodRange2" xlink:to="ions_MaximumContractMaturityPeriodRange2_lbl1" xlink:title="label: MaximumContractMaturityPeriodRange2 to ions_MaximumContractMaturityPeriodRange2_lbl1" />
    <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-20201231.xsd#ions_EquitySecuritiesPrivateCompaniesMember" xlink:label="EquitySecuritiesPrivateCompaniesMember" xlink:title="EquitySecuritiesPrivateCompaniesMember" />
    <link:label xlink:type="resource" xlink:label="ions_EquitySecuritiesPrivateCompaniesMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_EquitySecuritiesPrivateCompaniesMember_lbl" xml:lang="en-US" id="ions_EquitySecuritiesPrivateCompaniesMember_lbl">Ownership interest or right to acquire or dispose of ownership interest in private corporations and other legal entities for which ownership interest is represented by shares of common or preferred stock, convertible securities, stock rights, or stock warrants.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EquitySecuritiesPrivateCompaniesMember" xlink:to="ions_EquitySecuritiesPrivateCompaniesMember_lbl" xlink:title="label: EquitySecuritiesPrivateCompaniesMember to ions_EquitySecuritiesPrivateCompaniesMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_EquitySecuritiesPrivateCompaniesMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_EquitySecuritiesPrivateCompaniesMember_lbl1" xml:lang="en-US" id="ions_EquitySecuritiesPrivateCompaniesMember_lbl1">Equity Securities, Private Companies [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EquitySecuritiesPrivateCompaniesMember" xlink:to="ions_EquitySecuritiesPrivateCompaniesMember_lbl1" xlink:title="label: EquitySecuritiesPrivateCompaniesMember to ions_EquitySecuritiesPrivateCompaniesMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_EquitySecuritiesPrivateCompaniesMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_EquitySecuritiesPrivateCompaniesMember_lbl2" xml:lang="en-US" id="ions_EquitySecuritiesPrivateCompaniesMember_lbl2">Equity Securities in Private Companies [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EquitySecuritiesPrivateCompaniesMember" xlink:to="ions_EquitySecuritiesPrivateCompaniesMember_lbl2" xlink:title="label: EquitySecuritiesPrivateCompaniesMember to ions_EquitySecuritiesPrivateCompaniesMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20201231.xsd#ions_EquitySecuritiesPubliclyTradedCompaniesMember" xlink:label="EquitySecuritiesPubliclyTradedCompaniesMember" xlink:title="EquitySecuritiesPubliclyTradedCompaniesMember" />
    <link:label xlink:type="resource" xlink:label="ions_EquitySecuritiesPubliclyTradedCompaniesMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_EquitySecuritiesPubliclyTradedCompaniesMember_lbl" xml:lang="en-US" id="ions_EquitySecuritiesPubliclyTradedCompaniesMember_lbl">Ownership interest or right to acquire or dispose of ownership interest in publicly traded corporations and other legal entities for which ownership interest is represented by shares of common or preferred stock, convertible securities, stock rights, or stock warrants.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EquitySecuritiesPubliclyTradedCompaniesMember" xlink:to="ions_EquitySecuritiesPubliclyTradedCompaniesMember_lbl" xlink:title="label: EquitySecuritiesPubliclyTradedCompaniesMember to ions_EquitySecuritiesPubliclyTradedCompaniesMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_EquitySecuritiesPubliclyTradedCompaniesMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_EquitySecuritiesPubliclyTradedCompaniesMember_lbl1" xml:lang="en-US" id="ions_EquitySecuritiesPubliclyTradedCompaniesMember_lbl1">Equity Securities, Publicly Traded Companies [Member]</link:label>
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    <link:loc xlink:type="locator" xlink:href="ions-20201231.xsd#ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNi" xlink:label="DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNi" xlink:title="DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNi" />
    <link:label xlink:type="resource" xlink:label="ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNi_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNi_lbl" xml:lang="en-US" id="ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNi_lbl">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).</link:label>
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    <link:label xlink:type="resource" xlink:label="ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNi_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNi_lbl1" xml:lang="en-US" id="ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNi_lbl1">Debt Securities, Available-for-sale and Equity Securities, FV-NI</link:label>
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    <link:loc xlink:type="locator" xlink:href="ions-20201231.xsd#ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedLoss" xlink:label="DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedLoss" xlink:title="DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedLoss" />
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    <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-20201231.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-20201231.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-20201231.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-20201231.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-20201231.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-20201231.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-20201231.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-20201231.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-20201231.xsd#ions_PeriodBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers" xlink:label="PeriodBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers" xlink:title="PeriodBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers" />
    <link:label xlink:type="resource" xlink:label="ions_PeriodBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_PeriodBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers_lbl" xml:lang="en-US" id="ions_PeriodBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers_lbl">Period of time before a change in control of the Company when vesting will accelerate for options and RSUs outstanding as of the termination date for executive officers, in 'PnYnMnDTnHnMnS' format, for example, 'P1Y5M13D' represents the reported fact of one year, five months, and thirteen days.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PeriodBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers" xlink:to="ions_PeriodBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers_lbl" xlink:title="label: PeriodBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers to ions_PeriodBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_PeriodBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_PeriodBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers_lbl1" xml:lang="en-US" id="ions_PeriodBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers_lbl1">Period before change in control when vesting will accelerate for executive officers</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PeriodBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers" xlink:to="ions_PeriodBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers_lbl1" xlink:title="label: PeriodBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers to ions_PeriodBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_PeriodBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_PeriodBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers_lbl2" xml:lang="en-US" id="ions_PeriodBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers_lbl2">Period before change in control when vesting will accelerate for executive officers</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PeriodBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers" xlink:to="ions_PeriodBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers_lbl2" xlink:title="label: PeriodBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers to ions_PeriodBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20201231.xsd#ions_NumberOfExecutiveOfficersTerminatedBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers" xlink:label="NumberOfExecutiveOfficersTerminatedBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers" xlink:title="NumberOfExecutiveOfficersTerminatedBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfExecutiveOfficersTerminatedBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_NumberOfExecutiveOfficersTerminatedBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers_lbl" xml:lang="en-US" id="ions_NumberOfExecutiveOfficersTerminatedBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers_lbl">The number of executive officers terminated by the Company during the period that begins three months before and ends twelve months following a change in control of the Company when vesting will accelerate for options and RSUs outstanding as of the termination date for executive officers</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfExecutiveOfficersTerminatedBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers" xlink:to="ions_NumberOfExecutiveOfficersTerminatedBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers_lbl" xlink:title="label: NumberOfExecutiveOfficersTerminatedBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers to ions_NumberOfExecutiveOfficersTerminatedBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfExecutiveOfficersTerminatedBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_NumberOfExecutiveOfficersTerminatedBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers_lbl1" xml:lang="en-US" id="ions_NumberOfExecutiveOfficersTerminatedBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers_lbl1">Number of executive officers terminated before change in control when vesting will accelerate for executive officers</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfExecutiveOfficersTerminatedBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers" xlink:to="ions_NumberOfExecutiveOfficersTerminatedBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers_lbl1" xlink:title="label: NumberOfExecutiveOfficersTerminatedBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers to ions_NumberOfExecutiveOfficersTerminatedBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfExecutiveOfficersTerminatedBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_NumberOfExecutiveOfficersTerminatedBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers_lbl2" xml:lang="en-US" id="ions_NumberOfExecutiveOfficersTerminatedBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers_lbl2">Number of executive officers terminated before change in control when vesting will accelerate for executive officers</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfExecutiveOfficersTerminatedBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers" xlink:to="ions_NumberOfExecutiveOfficersTerminatedBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers_lbl2" xlink:title="label: NumberOfExecutiveOfficersTerminatedBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers to ions_NumberOfExecutiveOfficersTerminatedBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20201231.xsd#ions_NumberOfExecutiveOfficersTerminatingEmployment" xlink:label="NumberOfExecutiveOfficersTerminatingEmployment" xlink:title="NumberOfExecutiveOfficersTerminatingEmployment" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfExecutiveOfficersTerminatingEmployment_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_NumberOfExecutiveOfficersTerminatingEmployment_lbl" xml:lang="en-US" id="ions_NumberOfExecutiveOfficersTerminatingEmployment_lbl">The number of executive officers terminating employment with the company.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfExecutiveOfficersTerminatingEmployment" xlink:to="ions_NumberOfExecutiveOfficersTerminatingEmployment_lbl" xlink:title="label: NumberOfExecutiveOfficersTerminatingEmployment to ions_NumberOfExecutiveOfficersTerminatingEmployment_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfExecutiveOfficersTerminatingEmployment_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_NumberOfExecutiveOfficersTerminatingEmployment_lbl1" xml:lang="en-US" id="ions_NumberOfExecutiveOfficersTerminatingEmployment_lbl1">Number of executive officers terminating employment</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfExecutiveOfficersTerminatingEmployment" xlink:to="ions_NumberOfExecutiveOfficersTerminatingEmployment_lbl1" xlink:title="label: NumberOfExecutiveOfficersTerminatingEmployment to ions_NumberOfExecutiveOfficersTerminatingEmployment_lbl1" />
    <link:loc xlink:type="locator" xlink:href="ions-20201231.xsd#ions_ResearchDevelopmentAndPatentMember" xlink:label="ResearchDevelopmentAndPatentMember" xlink:title="ResearchDevelopmentAndPatentMember" />
    <link:label xlink:type="resource" xlink:label="ions_ResearchDevelopmentAndPatentMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_ResearchDevelopmentAndPatentMember_lbl" xml:lang="en-US" id="ions_ResearchDevelopmentAndPatentMember_lbl">Primary financial statement caption encompassing research, development and patent expenses.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ResearchDevelopmentAndPatentMember" xlink:to="ions_ResearchDevelopmentAndPatentMember_lbl" xlink:title="label: ResearchDevelopmentAndPatentMember to ions_ResearchDevelopmentAndPatentMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_ResearchDevelopmentAndPatentMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_ResearchDevelopmentAndPatentMember_lbl1" xml:lang="en-US" id="ions_ResearchDevelopmentAndPatentMember_lbl1">Research, Development and Patent [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ResearchDevelopmentAndPatentMember" xlink:to="ions_ResearchDevelopmentAndPatentMember_lbl1" xlink:title="label: ResearchDevelopmentAndPatentMember to ions_ResearchDevelopmentAndPatentMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_ResearchDevelopmentAndPatentMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_ResearchDevelopmentAndPatentMember_lbl2" xml:lang="en-US" id="ions_ResearchDevelopmentAndPatentMember_lbl2">Research, Development and Patent [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ResearchDevelopmentAndPatentMember" xlink:to="ions_ResearchDevelopmentAndPatentMember_lbl2" xlink:title="label: ResearchDevelopmentAndPatentMember to ions_ResearchDevelopmentAndPatentMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20201231.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-20201231.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-20201231.xsd#ions_WeightedAverageNumberOfSharesOwnedInSubsidiary" xlink:label="WeightedAverageNumberOfSharesOwnedInSubsidiary" xlink:title="WeightedAverageNumberOfSharesOwnedInSubsidiary" />
    <link:label xlink:type="resource" xlink:label="ions_WeightedAverageNumberOfSharesOwnedInSubsidiary_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_WeightedAverageNumberOfSharesOwnedInSubsidiary_lbl" xml:lang="en-US" id="ions_WeightedAverageNumberOfSharesOwnedInSubsidiary_lbl">Number of shares owned in the subsidiary during the reporting period determined by relating the portion of time within a reporting period that shares have been owned to the total time in that period.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="WeightedAverageNumberOfSharesOwnedInSubsidiary" xlink:to="ions_WeightedAverageNumberOfSharesOwnedInSubsidiary_lbl" xlink:title="label: WeightedAverageNumberOfSharesOwnedInSubsidiary to ions_WeightedAverageNumberOfSharesOwnedInSubsidiary_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_WeightedAverageNumberOfSharesOwnedInSubsidiary_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_WeightedAverageNumberOfSharesOwnedInSubsidiary_lbl1" xml:lang="en-US" id="ions_WeightedAverageNumberOfSharesOwnedInSubsidiary_lbl1">Weighted average number of shares owned in subsidiary</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="WeightedAverageNumberOfSharesOwnedInSubsidiary" xlink:to="ions_WeightedAverageNumberOfSharesOwnedInSubsidiary_lbl1" xlink:title="label: WeightedAverageNumberOfSharesOwnedInSubsidiary to ions_WeightedAverageNumberOfSharesOwnedInSubsidiary_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_WeightedAverageNumberOfSharesOwnedInSubsidiary_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_WeightedAverageNumberOfSharesOwnedInSubsidiary_lbl2" xml:lang="en-US" id="ions_WeightedAverageNumberOfSharesOwnedInSubsidiary_lbl2">Weighted average shares owned in Akcea (in shares)</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="WeightedAverageNumberOfSharesOwnedInSubsidiary" xlink:to="ions_WeightedAverageNumberOfSharesOwnedInSubsidiary_lbl2" xlink:title="label: WeightedAverageNumberOfSharesOwnedInSubsidiary to ions_WeightedAverageNumberOfSharesOwnedInSubsidiary_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20201231.xsd#ions_IncrementalCommonSharesAttributableToEmployeeStockPurchasePlan" xlink:label="IncrementalCommonSharesAttributableToEmployeeStockPurchasePlan" xlink:title="IncrementalCommonSharesAttributableToEmployeeStockPurchasePlan" />
    <link:label xlink:type="resource" xlink:label="ions_IncrementalCommonSharesAttributableToEmployeeStockPurchasePlan_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_IncrementalCommonSharesAttributableToEmployeeStockPurchasePlan_lbl" xml:lang="en-US" id="ions_IncrementalCommonSharesAttributableToEmployeeStockPurchasePlan_lbl">Additional shares included in the calculation of diluted EPS as a result of the potentially dilutive effect of shares issuable related to employee stock purchase plan.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IncrementalCommonSharesAttributableToEmployeeStockPurchasePlan" xlink:to="ions_IncrementalCommonSharesAttributableToEmployeeStockPurchasePlan_lbl" xlink:title="label: IncrementalCommonSharesAttributableToEmployeeStockPurchasePlan to ions_IncrementalCommonSharesAttributableToEmployeeStockPurchasePlan_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_IncrementalCommonSharesAttributableToEmployeeStockPurchasePlan_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_IncrementalCommonSharesAttributableToEmployeeStockPurchasePlan_lbl1" xml:lang="en-US" id="ions_IncrementalCommonSharesAttributableToEmployeeStockPurchasePlan_lbl1">Incremental Common Shares Attributable to Employee Stock Purchase Plan</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IncrementalCommonSharesAttributableToEmployeeStockPurchasePlan" xlink:to="ions_IncrementalCommonSharesAttributableToEmployeeStockPurchasePlan_lbl1" xlink:title="label: IncrementalCommonSharesAttributableToEmployeeStockPurchasePlan to ions_IncrementalCommonSharesAttributableToEmployeeStockPurchasePlan_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_IncrementalCommonSharesAttributableToEmployeeStockPurchasePlan_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_IncrementalCommonSharesAttributableToEmployeeStockPurchasePlan_lbl2" xml:lang="en-US" id="ions_IncrementalCommonSharesAttributableToEmployeeStockPurchasePlan_lbl2">Shares issuable related to our ESPP (in shares)</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IncrementalCommonSharesAttributableToEmployeeStockPurchasePlan" xlink:to="ions_IncrementalCommonSharesAttributableToEmployeeStockPurchasePlan_lbl2" xlink:title="label: IncrementalCommonSharesAttributableToEmployeeStockPurchasePlan to ions_IncrementalCommonSharesAttributableToEmployeeStockPurchasePlan_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20201231.xsd#ions_IncreaseDecreaseInAccruedLiabilitiesAndDeferredLiabilities" xlink:label="IncreaseDecreaseInAccruedLiabilitiesAndDeferredLiabilities" xlink:title="IncreaseDecreaseInAccruedLiabilitiesAndDeferredLiabilities" />
    <link:label xlink:type="resource" xlink:label="ions_IncreaseDecreaseInAccruedLiabilitiesAndDeferredLiabilities_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_IncreaseDecreaseInAccruedLiabilitiesAndDeferredLiabilities_lbl" xml:lang="en-US" id="ions_IncreaseDecreaseInAccruedLiabilitiesAndDeferredLiabilities_lbl">The increase (decrease) during the reporting period in the aggregate amount of expenses incurred but not yet paid and the change during the period in carrying value for all deferred liabilities due within one year or operating cycle.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IncreaseDecreaseInAccruedLiabilitiesAndDeferredLiabilities" xlink:to="ions_IncreaseDecreaseInAccruedLiabilitiesAndDeferredLiabilities_lbl" xlink:title="label: IncreaseDecreaseInAccruedLiabilitiesAndDeferredLiabilities to ions_IncreaseDecreaseInAccruedLiabilitiesAndDeferredLiabilities_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_IncreaseDecreaseInAccruedLiabilitiesAndDeferredLiabilities_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_IncreaseDecreaseInAccruedLiabilitiesAndDeferredLiabilities_lbl1" xml:lang="en-US" id="ions_IncreaseDecreaseInAccruedLiabilitiesAndDeferredLiabilities_lbl1">Increase (Decrease) in Accrued Liabilities and Deferred Liabilities</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IncreaseDecreaseInAccruedLiabilitiesAndDeferredLiabilities" xlink:to="ions_IncreaseDecreaseInAccruedLiabilitiesAndDeferredLiabilities_lbl1" xlink:title="label: IncreaseDecreaseInAccruedLiabilitiesAndDeferredLiabilities to ions_IncreaseDecreaseInAccruedLiabilitiesAndDeferredLiabilities_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_IncreaseDecreaseInAccruedLiabilitiesAndDeferredLiabilities_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_IncreaseDecreaseInAccruedLiabilitiesAndDeferredLiabilities_lbl2" xml:lang="en-US" id="ions_IncreaseDecreaseInAccruedLiabilitiesAndDeferredLiabilities_lbl2">Accrued liabilities and deferred rent</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IncreaseDecreaseInAccruedLiabilitiesAndDeferredLiabilities" xlink:to="ions_IncreaseDecreaseInAccruedLiabilitiesAndDeferredLiabilities_lbl2" xlink:title="label: IncreaseDecreaseInAccruedLiabilitiesAndDeferredLiabilities to ions_IncreaseDecreaseInAccruedLiabilitiesAndDeferredLiabilities_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20201231.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-20201231.xsd#ions_OtherComprehensiveIncomeLossAdjustmentsFromPurchaseOfNoncontrollingInterestOfSubsidiary" xlink:label="OtherComprehensiveIncomeLossAdjustmentsFromPurchaseOfNoncontrollingInterestOfSubsidiary" xlink:title="OtherComprehensiveIncomeLossAdjustmentsFromPurchaseOfNoncontrollingInterestOfSubsidiary" />
    <link:label xlink:type="resource" xlink:label="ions_OtherComprehensiveIncomeLossAdjustmentsFromPurchaseOfNoncontrollingInterestOfSubsidiary_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_OtherComprehensiveIncomeLossAdjustmentsFromPurchaseOfNoncontrollingInterestOfSubsidiary_lbl" xml:lang="en-US" id="ions_OtherComprehensiveIncomeLossAdjustmentsFromPurchaseOfNoncontrollingInterestOfSubsidiary_lbl">Adjustments to other comprehensive income (loss) from purchase of noncontrolling interest of subsidiary.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OtherComprehensiveIncomeLossAdjustmentsFromPurchaseOfNoncontrollingInterestOfSubsidiary" xlink:to="ions_OtherComprehensiveIncomeLossAdjustmentsFromPurchaseOfNoncontrollingInterestOfSubsidiary_lbl" xlink:title="label: OtherComprehensiveIncomeLossAdjustmentsFromPurchaseOfNoncontrollingInterestOfSubsidiary to ions_OtherComprehensiveIncomeLossAdjustmentsFromPurchaseOfNoncontrollingInterestOfSubsidiary_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_OtherComprehensiveIncomeLossAdjustmentsFromPurchaseOfNoncontrollingInterestOfSubsidiary_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_OtherComprehensiveIncomeLossAdjustmentsFromPurchaseOfNoncontrollingInterestOfSubsidiary_lbl1" xml:lang="en-US" id="ions_OtherComprehensiveIncomeLossAdjustmentsFromPurchaseOfNoncontrollingInterestOfSubsidiary_lbl1">Other Comprehensive Income (Loss), Adjustments from Purchase of Noncontrolling Interest of Subsidiary</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OtherComprehensiveIncomeLossAdjustmentsFromPurchaseOfNoncontrollingInterestOfSubsidiary" xlink:to="ions_OtherComprehensiveIncomeLossAdjustmentsFromPurchaseOfNoncontrollingInterestOfSubsidiary_lbl1" xlink:title="label: OtherComprehensiveIncomeLossAdjustmentsFromPurchaseOfNoncontrollingInterestOfSubsidiary to ions_OtherComprehensiveIncomeLossAdjustmentsFromPurchaseOfNoncontrollingInterestOfSubsidiary_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_OtherComprehensiveIncomeLossAdjustmentsFromPurchaseOfNoncontrollingInterestOfSubsidiary_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_OtherComprehensiveIncomeLossAdjustmentsFromPurchaseOfNoncontrollingInterestOfSubsidiary_lbl2" xml:lang="en-US" id="ions_OtherComprehensiveIncomeLossAdjustmentsFromPurchaseOfNoncontrollingInterestOfSubsidiary_lbl2">Adjustments to other comprehensive loss from purchase of noncontrolling interest of Akcea Therapeutics, Inc.</link:label>
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    <link:loc xlink:type="locator" xlink:href="ions-20201231.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-20201231.xsd#ions_IonisCoreMember" xlink:label="IonisCoreMember" xlink:title="IonisCoreMember" />
    <link:label xlink:type="resource" xlink:label="ions_IonisCoreMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_IonisCoreMember_lbl" xml:lang="en-US" id="ions_IonisCoreMember_lbl">Reportable segment in which the Company is exploiting a novel drug discovery platform created to generate a broad pipeline of first-in-class or best-in-class drugs for the Company and its partners. This segment generates revenue from a multifaceted partnering strategy. This strategy includes revenue from collaborations with preferred partners, traditional alliances and working with a consortium of companies that can exploit the Company's drugs and technology. Revenue from collaborations with preferred partners and traditional alliances may consist of upfront payments, milestone payments, licensing fees and royalties.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IonisCoreMember" xlink:to="ions_IonisCoreMember_lbl" xlink:title="label: IonisCoreMember to ions_IonisCoreMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_IonisCoreMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_IonisCoreMember_lbl1" xml:lang="en-US" id="ions_IonisCoreMember_lbl1">Ionis Core [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IonisCoreMember" xlink:to="ions_IonisCoreMember_lbl1" xlink:title="label: IonisCoreMember to ions_IonisCoreMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_IonisCoreMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_IonisCoreMember_lbl2" xml:lang="en-US" id="ions_IonisCoreMember_lbl2">Ionis [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IonisCoreMember" xlink:to="ions_IonisCoreMember_lbl2" xlink:title="label: IonisCoreMember to ions_IonisCoreMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20201231.xsd#ions_AkceaTherapeuticsMember" xlink:label="AkceaTherapeuticsMember" xlink:title="AkceaTherapeuticsMember" />
    <link:label xlink:type="resource" xlink:label="ions_AkceaTherapeuticsMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_AkceaTherapeuticsMember_lbl" xml:lang="en-US" id="ions_AkceaTherapeuticsMember_lbl">Reportable segment which includes the operations of the Company's wholly-owned subsidiary, Akcea Therapeutics, Inc., which was formed to develop and commercialize drugs for cardiometabolic disorders.</link:label>
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    <link:label xlink:type="resource" xlink:label="ions_AkceaTherapeuticsMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_AkceaTherapeuticsMember_lbl1" xml:lang="en-US" id="ions_AkceaTherapeuticsMember_lbl1">Akcea Therapeutics [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AkceaTherapeuticsMember" xlink:to="ions_AkceaTherapeuticsMember_lbl1" xlink:title="label: AkceaTherapeuticsMember to ions_AkceaTherapeuticsMember_lbl1" />
    <link:loc xlink:type="locator" xlink:href="ions-20201231.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>
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    <link:loc xlink:type="locator" xlink:href="ions-20201231.xsd#ions_ShareBasedCompensationLineItems" xlink:label="ShareBasedCompensationLineItems" xlink:title="ShareBasedCompensationLineItems" />
    <link:label xlink:type="resource" xlink:label="ions_ShareBasedCompensationLineItems_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_ShareBasedCompensationLineItems_lbl" xml:lang="en-US" id="ions_ShareBasedCompensationLineItems_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="ShareBasedCompensationLineItems" xlink:to="ions_ShareBasedCompensationLineItems_lbl" xlink:title="label: ShareBasedCompensationLineItems to ions_ShareBasedCompensationLineItems_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_ShareBasedCompensationLineItems_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_ShareBasedCompensationLineItems_lbl1" xml:lang="en-US" id="ions_ShareBasedCompensationLineItems_lbl1">Share-based Compensation [Line Items]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedCompensationLineItems" xlink:to="ions_ShareBasedCompensationLineItems_lbl1" xlink:title="label: ShareBasedCompensationLineItems to ions_ShareBasedCompensationLineItems_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_ShareBasedCompensationLineItems_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_ShareBasedCompensationLineItems_lbl2" xml:lang="en-US" id="ions_ShareBasedCompensationLineItems_lbl2">Stockholders' Equity [Abstract]</link:label>
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    <link:loc xlink:type="locator" xlink:href="ions-20201231.xsd#ions_ShareBasedCompensationTable" xlink:label="ShareBasedCompensationTable" xlink:title="ShareBasedCompensationTable" />
    <link:label xlink:type="resource" xlink:label="ions_ShareBasedCompensationTable_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_ShareBasedCompensationTable_lbl" xml:lang="en-US" id="ions_ShareBasedCompensationTable_lbl">Disclosure of information about share-based compensation.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedCompensationTable" xlink:to="ions_ShareBasedCompensationTable_lbl" xlink:title="label: ShareBasedCompensationTable to ions_ShareBasedCompensationTable_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_ShareBasedCompensationTable_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_ShareBasedCompensationTable_lbl1" xml:lang="en-US" id="ions_ShareBasedCompensationTable_lbl1">Share-based Compensation [Table]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedCompensationTable" xlink:to="ions_ShareBasedCompensationTable_lbl1" xlink:title="label: ShareBasedCompensationTable to ions_ShareBasedCompensationTable_lbl1" />
    <link:loc xlink:type="locator" xlink:href="ions-20201231.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-20201231.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 partially 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-20201231.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-20201231.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>
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    <link:loc xlink:type="locator" xlink:href="ions-20201231.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-20201231.xsd#ions_PropertyPlantAndEquipmentExcludingLandMember" xlink:label="PropertyPlantAndEquipmentExcludingLandMember" xlink:title="PropertyPlantAndEquipmentExcludingLandMember" />
    <link:label xlink:type="resource" xlink:label="ions_PropertyPlantAndEquipmentExcludingLandMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_PropertyPlantAndEquipmentExcludingLandMember_lbl" xml:lang="en-US" id="ions_PropertyPlantAndEquipmentExcludingLandMember_lbl">Physical assets used in the normal conduct of business and not intended for resale, excluding land. Examples include, but are not limited to, buildings, land and leasehold improvements, machinery and equipment, office equipment, and furniture and fixtures.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PropertyPlantAndEquipmentExcludingLandMember" xlink:to="ions_PropertyPlantAndEquipmentExcludingLandMember_lbl" xlink:title="label: PropertyPlantAndEquipmentExcludingLandMember to ions_PropertyPlantAndEquipmentExcludingLandMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_PropertyPlantAndEquipmentExcludingLandMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_PropertyPlantAndEquipmentExcludingLandMember_lbl1" xml:lang="en-US" id="ions_PropertyPlantAndEquipmentExcludingLandMember_lbl1">Property, Plant and Equipment, Excluding Land [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PropertyPlantAndEquipmentExcludingLandMember" xlink:to="ions_PropertyPlantAndEquipmentExcludingLandMember_lbl1" xlink:title="label: PropertyPlantAndEquipmentExcludingLandMember to ions_PropertyPlantAndEquipmentExcludingLandMember_lbl1" />
    <link:loc xlink:type="locator" xlink:href="ions-20201231.xsd#ions_DebtInstrumentConvertibleConversionPriceIncludingCallSpread" xlink:label="DebtInstrumentConvertibleConversionPriceIncludingCallSpread" xlink:title="DebtInstrumentConvertibleConversionPriceIncludingCallSpread" />
    <link:label xlink:type="resource" xlink:label="ions_DebtInstrumentConvertibleConversionPriceIncludingCallSpread_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_DebtInstrumentConvertibleConversionPriceIncludingCallSpread_lbl" xml:lang="en-US" id="ions_DebtInstrumentConvertibleConversionPriceIncludingCallSpread_lbl">The computed conversion price per share of the debt instrument based on the the conversion feature embedded in the debt instrument and the impact of the purchased hedges in the call spread transaction.</link:label>
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtInstrumentConvertibleConversionPriceIncludingCallSpread" xlink:to="ions_DebtInstrumentConvertibleConversionPriceIncludingCallSpread_lbl2" xlink:title="label: DebtInstrumentConvertibleConversionPriceIncludingCallSpread to ions_DebtInstrumentConvertibleConversionPriceIncludingCallSpread_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20201231.xsd#ions_CallSpread" xlink:label="CallSpread" xlink:title="CallSpread" />
    <link:label xlink:type="resource" xlink:label="ions_CallSpread_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_CallSpread_lbl" xml:lang="en-US" id="ions_CallSpread_lbl">The net cash outflow from payments for hedge transactions and proceeds from the issuance of warrants. The call spread transaction was entered into to minimize the impact of potential economic dilution upon conversion of the 0.125% notes issued.</link:label>
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    <link:label xlink:type="resource" xlink:label="ions_CallSpread_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_CallSpread_lbl1" xml:lang="en-US" id="ions_CallSpread_lbl1">Call Spread</link:label>
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    <link:label xlink:type="resource" xlink:label="ions_CallSpread_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_CallSpread_lbl2" xml:lang="en-US" id="ions_CallSpread_lbl2">Cost of call spread</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CallSpread" xlink:to="ions_CallSpread_lbl2" xlink:title="label: CallSpread to ions_CallSpread_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20201231.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>
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    <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>
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    <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 Percent 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-20201231.xsd#ions_ConvertibleSeniorNotes0125PercentIssuedInExchangeFor1PercentNotesMember" xlink:label="ConvertibleSeniorNotes0125PercentIssuedInExchangeFor1PercentNotesMember" xlink:title="ConvertibleSeniorNotes0125PercentIssuedInExchangeFor1PercentNotesMember" />
    <link:label xlink:type="resource" xlink:label="ions_ConvertibleSeniorNotes0125PercentIssuedInExchangeFor1PercentNotesMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_ConvertibleSeniorNotes0125PercentIssuedInExchangeFor1PercentNotesMember_lbl" xml:lang="en-US" id="ions_ConvertibleSeniorNotes0125PercentIssuedInExchangeFor1PercentNotesMember_lbl">0.125 percent convertible senior notes due December 2024 that were issued in exchange for 1 percent notes in December 2019.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleSeniorNotes0125PercentIssuedInExchangeFor1PercentNotesMember" xlink:to="ions_ConvertibleSeniorNotes0125PercentIssuedInExchangeFor1PercentNotesMember_lbl" xlink:title="label: ConvertibleSeniorNotes0125PercentIssuedInExchangeFor1PercentNotesMember to ions_ConvertibleSeniorNotes0125PercentIssuedInExchangeFor1PercentNotesMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_ConvertibleSeniorNotes0125PercentIssuedInExchangeFor1PercentNotesMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_ConvertibleSeniorNotes0125PercentIssuedInExchangeFor1PercentNotesMember_lbl1" xml:lang="en-US" id="ions_ConvertibleSeniorNotes0125PercentIssuedInExchangeFor1PercentNotesMember_lbl1">Convertible Senior Notes 0.125 Percent, Issued in Exchange for 1 Percent Notes [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleSeniorNotes0125PercentIssuedInExchangeFor1PercentNotesMember" xlink:to="ions_ConvertibleSeniorNotes0125PercentIssuedInExchangeFor1PercentNotesMember_lbl1" xlink:title="label: ConvertibleSeniorNotes0125PercentIssuedInExchangeFor1PercentNotesMember to ions_ConvertibleSeniorNotes0125PercentIssuedInExchangeFor1PercentNotesMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_ConvertibleSeniorNotes0125PercentIssuedInExchangeFor1PercentNotesMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_ConvertibleSeniorNotes0125PercentIssuedInExchangeFor1PercentNotesMember_lbl2" xml:lang="en-US" id="ions_ConvertibleSeniorNotes0125PercentIssuedInExchangeFor1PercentNotesMember_lbl2">0.125 Percent Convertible Senior Notes Issued in Exchange for 1 Percent Notes [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleSeniorNotes0125PercentIssuedInExchangeFor1PercentNotesMember" xlink:to="ions_ConvertibleSeniorNotes0125PercentIssuedInExchangeFor1PercentNotesMember_lbl2" xlink:title="label: ConvertibleSeniorNotes0125PercentIssuedInExchangeFor1PercentNotesMember to ions_ConvertibleSeniorNotes0125PercentIssuedInExchangeFor1PercentNotesMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20201231.xsd#ions_ConvertibleSeniorNotes275PercentMember" xlink:label="ConvertibleSeniorNotes275PercentMember" xlink:title="ConvertibleSeniorNotes275PercentMember" />
    <link:label xlink:type="resource" xlink:label="ions_ConvertibleSeniorNotes275PercentMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_ConvertibleSeniorNotes275PercentMember_lbl" xml:lang="en-US" id="ions_ConvertibleSeniorNotes275PercentMember_lbl">2 3/4 percent convertible senior notes due October 2019.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleSeniorNotes275PercentMember" xlink:to="ions_ConvertibleSeniorNotes275PercentMember_lbl" xlink:title="label: ConvertibleSeniorNotes275PercentMember to ions_ConvertibleSeniorNotes275PercentMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_ConvertibleSeniorNotes275PercentMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_ConvertibleSeniorNotes275PercentMember_lbl1" xml:lang="en-US" id="ions_ConvertibleSeniorNotes275PercentMember_lbl1">Convertible Senior Notes 2.75 Percent [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleSeniorNotes275PercentMember" xlink:to="ions_ConvertibleSeniorNotes275PercentMember_lbl1" xlink:title="label: ConvertibleSeniorNotes275PercentMember to ions_ConvertibleSeniorNotes275PercentMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_ConvertibleSeniorNotes275PercentMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_ConvertibleSeniorNotes275PercentMember_lbl2" xml:lang="en-US" id="ions_ConvertibleSeniorNotes275PercentMember_lbl2">2 3/4 Percent Convertible Senior Notes [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleSeniorNotes275PercentMember" xlink:to="ions_ConvertibleSeniorNotes275PercentMember_lbl2" xlink:title="label: ConvertibleSeniorNotes275PercentMember to ions_ConvertibleSeniorNotes275PercentMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20201231.xsd#ions_DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange" xlink:label="DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange" xlink:title="DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange" />
    <link:label xlink:type="resource" xlink:label="ions_DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange_lbl" xml:lang="en-US" id="ions_DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange_lbl">The percentage of the principal amount of the notes to be purchased, plus accrued and unpaid interest, upon the occurrence of certain fundamental changes, as set forth in the indenture governing the convertible notes.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange" xlink:to="ions_DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange_lbl" xlink:title="label: DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange to ions_DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange_lbl1" xml:lang="en-US" id="ions_DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange_lbl1">Debt Instrument, Convertible, Percentage of principal amount used as purchase price upon occurrence of fundamental change</link:label>
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    <link:label xlink:type="resource" xlink:label="ions_DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange_lbl2" xml:lang="en-US" id="ions_DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange_lbl2">Percentage of principal amount used as purchase price upon occurrence of fundamental change</link:label>
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    <link:loc xlink:type="locator" xlink:href="ions-20201231.xsd#ions_EffectiveIncomeTaxRateReconciliationAcquisitionOfNoncontrollingInterestPercent" xlink:label="EffectiveIncomeTaxRateReconciliationAcquisitionOfNoncontrollingInterestPercent" xlink:title="EffectiveIncomeTaxRateReconciliationAcquisitionOfNoncontrollingInterestPercent" />
    <link:label xlink:type="resource" xlink:label="ions_EffectiveIncomeTaxRateReconciliationAcquisitionOfNoncontrollingInterestPercent_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_EffectiveIncomeTaxRateReconciliationAcquisitionOfNoncontrollingInterestPercent_lbl" xml:lang="en-US" id="ions_EffectiveIncomeTaxRateReconciliationAcquisitionOfNoncontrollingInterestPercent_lbl">Percentage of the difference between reported income tax expense (benefit) and expected income tax expense (benefit) computed by applying the domestic federal statutory income tax rates to pretax income (loss) from continuing operations attributable to acquisition of noncontrolling interest.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EffectiveIncomeTaxRateReconciliationAcquisitionOfNoncontrollingInterestPercent" xlink:to="ions_EffectiveIncomeTaxRateReconciliationAcquisitionOfNoncontrollingInterestPercent_lbl" xlink:title="label: EffectiveIncomeTaxRateReconciliationAcquisitionOfNoncontrollingInterestPercent to ions_EffectiveIncomeTaxRateReconciliationAcquisitionOfNoncontrollingInterestPercent_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_EffectiveIncomeTaxRateReconciliationAcquisitionOfNoncontrollingInterestPercent_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_EffectiveIncomeTaxRateReconciliationAcquisitionOfNoncontrollingInterestPercent_lbl1" xml:lang="en-US" id="ions_EffectiveIncomeTaxRateReconciliationAcquisitionOfNoncontrollingInterestPercent_lbl1">Effective Income Tax Rate Reconciliation, Acquisition of Noncontrolling Interest, Percent</link:label>
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    <link:label xlink:type="resource" xlink:label="ions_EffectiveIncomeTaxRateReconciliationAcquisitionOfNoncontrollingInterestPercent_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_EffectiveIncomeTaxRateReconciliationAcquisitionOfNoncontrollingInterestPercent_lbl2" xml:lang="en-US" id="ions_EffectiveIncomeTaxRateReconciliationAcquisitionOfNoncontrollingInterestPercent_lbl2">Impacts from Akcea Acquisition</link:label>
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    <link:loc xlink:type="locator" xlink:href="ions-20201231.xsd#ions_EffectiveIncomeTaxRateReconciliationDeconsolidationAdjustmentForSubsidiaryAtIpoPercent" xlink:label="EffectiveIncomeTaxRateReconciliationDeconsolidationAdjustmentForSubsidiaryAtIpoPercent" xlink:title="EffectiveIncomeTaxRateReconciliationDeconsolidationAdjustmentForSubsidiaryAtIpoPercent" />
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    <link:loc xlink:type="locator" xlink:href="ions-20201231.xsd#ions_EffectiveIncomeTaxRateReconciliationExpirationOfNetOperatingLossAmount" xlink:label="EffectiveIncomeTaxRateReconciliationExpirationOfNetOperatingLossAmount" xlink:title="EffectiveIncomeTaxRateReconciliationExpirationOfNetOperatingLossAmount" />
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    <link:loc xlink:type="locator" xlink:href="ions-20201231.xsd#ions_EffectiveIncomeTaxRateReconciliationImpactFromOutsideBasisDifferencesPercent" xlink:label="EffectiveIncomeTaxRateReconciliationImpactFromOutsideBasisDifferencesPercent" xlink:title="EffectiveIncomeTaxRateReconciliationImpactFromOutsideBasisDifferencesPercent" />
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    <link:loc xlink:type="locator" xlink:href="ions-20201231.xsd#ions_EffectiveIncomeTaxRateReconciliationImpactFromOutsideBasisDifferencesAmount" xlink:label="EffectiveIncomeTaxRateReconciliationImpactFromOutsideBasisDifferencesAmount" xlink:title="EffectiveIncomeTaxRateReconciliationImpactFromOutsideBasisDifferencesAmount" />
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    <link:loc xlink:type="locator" xlink:href="ions-20201231.xsd#ions_DeferredTaxAssetsLiabilitiesNetBeforeValuationAllowance" xlink:label="DeferredTaxAssetsLiabilitiesNetBeforeValuationAllowance" xlink:title="DeferredTaxAssetsLiabilitiesNetBeforeValuationAllowance" />
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    <link:loc xlink:type="locator" xlink:href="ions-20201231.xsd#ions_PeriodAfterBillingWhenPaymentIsReceived" xlink:label="PeriodAfterBillingWhenPaymentIsReceived" xlink:title="PeriodAfterBillingWhenPaymentIsReceived" />
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    <link:loc xlink:type="locator" xlink:href="ions-20201231.xsd#ions_LicensingAndOtherRoyaltiesMember" xlink:label="LicensingAndOtherRoyaltiesMember" xlink:title="LicensingAndOtherRoyaltiesMember" />
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    <link:loc xlink:type="locator" xlink:href="ions-20201231.xsd#ions_SpinrazaRoyaltiesMember" xlink:label="SpinrazaRoyaltiesMember" xlink:title="SpinrazaRoyaltiesMember" />
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    <link:loc xlink:type="locator" xlink:href="ions-20201231.xsd#ions_CommercialMember" xlink:label="CommercialMember" xlink:title="CommercialMember" />
    <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-20201231.xsd#ions_ResearchDevelopmentAndPatentExpense" xlink:label="ResearchDevelopmentAndPatentExpense" xlink:title="ResearchDevelopmentAndPatentExpense" />
    <link:label xlink:type="resource" xlink:label="ions_ResearchDevelopmentAndPatentExpense_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_ResearchDevelopmentAndPatentExpense_lbl" xml:lang="en-US" id="ions_ResearchDevelopmentAndPatentExpense_lbl">The aggregate costs incurred (1) in a planned search or critical investigation aimed at discovery of new knowledge with the hope that such knowledge will be useful in developing a new product or service, a new process or technique, or in bringing about a significant improvement to an existing product or process; or (2) to translate research findings or other knowledge into a plan or design for a new product or process or for a significant improvement to an existing product or process whether intended for sale or the entity's use, during the reporting period charged to research and development projects. Also includes charges for amortization and write-downs of capitalized patent costs, as well as legal fees for patent litigation and patent defense.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ResearchDevelopmentAndPatentExpense" xlink:to="ions_ResearchDevelopmentAndPatentExpense_lbl" xlink:title="label: ResearchDevelopmentAndPatentExpense to ions_ResearchDevelopmentAndPatentExpense_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_ResearchDevelopmentAndPatentExpense_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_ResearchDevelopmentAndPatentExpense_lbl1" xml:lang="en-US" id="ions_ResearchDevelopmentAndPatentExpense_lbl1">Research, Development and Patent Expense</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ResearchDevelopmentAndPatentExpense" xlink:to="ions_ResearchDevelopmentAndPatentExpense_lbl1" xlink:title="label: ResearchDevelopmentAndPatentExpense to ions_ResearchDevelopmentAndPatentExpense_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_ResearchDevelopmentAndPatentExpense_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_ResearchDevelopmentAndPatentExpense_lbl2" xml:lang="en-US" id="ions_ResearchDevelopmentAndPatentExpense_lbl2">Research, development and patent</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ResearchDevelopmentAndPatentExpense" xlink:to="ions_ResearchDevelopmentAndPatentExpense_lbl2" xlink:title="label: ResearchDevelopmentAndPatentExpense to ions_ResearchDevelopmentAndPatentExpense_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20201231.xsd#ions_ResearchAndDevelopmentServicesForVupanorsenMember" xlink:label="ResearchAndDevelopmentServicesForVupanorsenMember" xlink:title="ResearchAndDevelopmentServicesForVupanorsenMember" />
    <link:label xlink:type="resource" xlink:label="ions_ResearchAndDevelopmentServicesForVupanorsenMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_ResearchAndDevelopmentServicesForVupanorsenMember_lbl" xml:lang="en-US" id="ions_ResearchAndDevelopmentServicesForVupanorsenMember_lbl">Research and development (R&amp;D) services for Vupanorsen, a ligand-conjugated (LICA) investigational antisense medicine designed to reduce angiopoietin-like 3 protein, or ANGPTL3.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ResearchAndDevelopmentServicesForVupanorsenMember" xlink:to="ions_ResearchAndDevelopmentServicesForVupanorsenMember_lbl" xlink:title="label: ResearchAndDevelopmentServicesForVupanorsenMember to ions_ResearchAndDevelopmentServicesForVupanorsenMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_ResearchAndDevelopmentServicesForVupanorsenMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_ResearchAndDevelopmentServicesForVupanorsenMember_lbl1" xml:lang="en-US" id="ions_ResearchAndDevelopmentServicesForVupanorsenMember_lbl1">Research and Development Services for Vupanorsen [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ResearchAndDevelopmentServicesForVupanorsenMember" xlink:to="ions_ResearchAndDevelopmentServicesForVupanorsenMember_lbl1" xlink:title="label: ResearchAndDevelopmentServicesForVupanorsenMember to ions_ResearchAndDevelopmentServicesForVupanorsenMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_ResearchAndDevelopmentServicesForVupanorsenMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_ResearchAndDevelopmentServicesForVupanorsenMember_lbl2" xml:lang="en-US" id="ions_ResearchAndDevelopmentServicesForVupanorsenMember_lbl2">R&amp;D Services for Vupanorsen [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ResearchAndDevelopmentServicesForVupanorsenMember" xlink:to="ions_ResearchAndDevelopmentServicesForVupanorsenMember_lbl2" xlink:title="label: ResearchAndDevelopmentServicesForVupanorsenMember to ions_ResearchAndDevelopmentServicesForVupanorsenMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20201231.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-20201231.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-20201231.xsd#ions_NextPotentialPayment" xlink:label="NextPotentialPayment" xlink:title="NextPotentialPayment" />
    <link:label xlink:type="resource" xlink:label="ions_NextPotentialPayment_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_NextPotentialPayment_lbl" xml:lang="en-US" id="ions_NextPotentialPayment_lbl">The next potential payment to be earned under the collaboration agreement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NextPotentialPayment" xlink:to="ions_NextPotentialPayment_lbl" xlink:title="label: NextPotentialPayment to ions_NextPotentialPayment_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_NextPotentialPayment_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_NextPotentialPayment_lbl1" xml:lang="en-US" id="ions_NextPotentialPayment_lbl1">Next potential payment</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NextPotentialPayment" xlink:to="ions_NextPotentialPayment_lbl1" xlink:title="label: NextPotentialPayment to ions_NextPotentialPayment_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_NextPotentialPayment_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_NextPotentialPayment_lbl2" xml:lang="en-US" id="ions_NextPotentialPayment_lbl2">Next prospective payment</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NextPotentialPayment" xlink:to="ions_NextPotentialPayment_lbl2" xlink:title="label: NextPotentialPayment to ions_NextPotentialPayment_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20201231.xsd#ions_MaximumAmountOfPaymentsReceivableForCommercializationMilestones" xlink:label="MaximumAmountOfPaymentsReceivableForCommercializationMilestones" xlink:title="MaximumAmountOfPaymentsReceivableForCommercializationMilestones" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfPaymentsReceivableForCommercializationMilestones_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_MaximumAmountOfPaymentsReceivableForCommercializationMilestones_lbl" xml:lang="en-US" id="ions_MaximumAmountOfPaymentsReceivableForCommercializationMilestones_lbl">The maximum amount of payments receivable for commercialization milestones under the collaboration agreement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfPaymentsReceivableForCommercializationMilestones" xlink:to="ions_MaximumAmountOfPaymentsReceivableForCommercializationMilestones_lbl" xlink:title="label: MaximumAmountOfPaymentsReceivableForCommercializationMilestones to ions_MaximumAmountOfPaymentsReceivableForCommercializationMilestones_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfPaymentsReceivableForCommercializationMilestones_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_MaximumAmountOfPaymentsReceivableForCommercializationMilestones_lbl1" xml:lang="en-US" id="ions_MaximumAmountOfPaymentsReceivableForCommercializationMilestones_lbl1">Maximum amount of payments receivable for commercialization milestones</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfPaymentsReceivableForCommercializationMilestones" xlink:to="ions_MaximumAmountOfPaymentsReceivableForCommercializationMilestones_lbl1" xlink:title="label: MaximumAmountOfPaymentsReceivableForCommercializationMilestones to ions_MaximumAmountOfPaymentsReceivableForCommercializationMilestones_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfPaymentsReceivableForCommercializationMilestones_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_MaximumAmountOfPaymentsReceivableForCommercializationMilestones_lbl2" xml:lang="en-US" id="ions_MaximumAmountOfPaymentsReceivableForCommercializationMilestones_lbl2">Maximum amount of payments receivable for commercialization milestones</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfPaymentsReceivableForCommercializationMilestones" xlink:to="ions_MaximumAmountOfPaymentsReceivableForCommercializationMilestones_lbl2" xlink:title="label: MaximumAmountOfPaymentsReceivableForCommercializationMilestones to ions_MaximumAmountOfPaymentsReceivableForCommercializationMilestones_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20201231.xsd#ions_MaximumAmountOfPaymentsReceivableForRegulatoryMilestones" xlink:label="MaximumAmountOfPaymentsReceivableForRegulatoryMilestones" xlink:title="MaximumAmountOfPaymentsReceivableForRegulatoryMilestones" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfPaymentsReceivableForRegulatoryMilestones_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_MaximumAmountOfPaymentsReceivableForRegulatoryMilestones_lbl" xml:lang="en-US" id="ions_MaximumAmountOfPaymentsReceivableForRegulatoryMilestones_lbl">The maximum amount of payments receivable for regulatory milestones under the collaboration agreement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfPaymentsReceivableForRegulatoryMilestones" xlink:to="ions_MaximumAmountOfPaymentsReceivableForRegulatoryMilestones_lbl" xlink:title="label: MaximumAmountOfPaymentsReceivableForRegulatoryMilestones to ions_MaximumAmountOfPaymentsReceivableForRegulatoryMilestones_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfPaymentsReceivableForRegulatoryMilestones_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_MaximumAmountOfPaymentsReceivableForRegulatoryMilestones_lbl1" xml:lang="en-US" id="ions_MaximumAmountOfPaymentsReceivableForRegulatoryMilestones_lbl1">Maximum amount of payments receivable for regulatory milestones</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfPaymentsReceivableForRegulatoryMilestones" xlink:to="ions_MaximumAmountOfPaymentsReceivableForRegulatoryMilestones_lbl1" xlink:title="label: MaximumAmountOfPaymentsReceivableForRegulatoryMilestones to ions_MaximumAmountOfPaymentsReceivableForRegulatoryMilestones_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfPaymentsReceivableForRegulatoryMilestones_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_MaximumAmountOfPaymentsReceivableForRegulatoryMilestones_lbl2" xml:lang="en-US" id="ions_MaximumAmountOfPaymentsReceivableForRegulatoryMilestones_lbl2">Maximum amount of payments receivable for regulatory milestones</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfPaymentsReceivableForRegulatoryMilestones" xlink:to="ions_MaximumAmountOfPaymentsReceivableForRegulatoryMilestones_lbl2" xlink:title="label: MaximumAmountOfPaymentsReceivableForRegulatoryMilestones to ions_MaximumAmountOfPaymentsReceivableForRegulatoryMilestones_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20201231.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-20201231.xsd#ions_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember" xlink:label="ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember" xlink:title="ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember" />
    <link:label xlink:type="resource" xlink:label="ions_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_lbl" xml:lang="en-US" id="ions_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_lbl">Revenue from research and development services performed under a collaboration agreement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember" xlink:to="ions_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_lbl" xlink:title="label: ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember to ions_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_lbl1" xml:lang="en-US" id="ions_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_lbl1">Research and Development Revenue Under Collaborative Agreements [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember" xlink:to="ions_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_lbl1" xlink:title="label: ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember to ions_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="ions_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_lbl2" xml:lang="en-US" id="ions_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_lbl2">R&amp;D Revenue Under Collaborative Agreements [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember" xlink:to="ions_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_lbl2" xlink:title="label: ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember to ions_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_lbl2" />
    <link:label xlink:type="resource" xlink:label="ions_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_lbl3" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_lbl3" xml:lang="en-US" id="ions_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_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="ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember" xlink:to="ions_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_lbl3" xlink:title="label: ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember to ions_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_lbl3" />
    <link:loc xlink:type="locator" xlink:href="ions-20201231.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-20201231.xsd#ions_VupanorsenMember" xlink:label="VupanorsenMember" xlink:title="VupanorsenMember" />
    <link:label xlink:type="resource" xlink:label="ions_VupanorsenMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_VupanorsenMember_lbl" xml:lang="en-US" id="ions_VupanorsenMember_lbl">Vupanorsen, formerly known as IONIS-ANGPTL3-LRx and AKCEA-ANGPTL3-LRx, is a ligand-conjugated (LICA) investigational antisense medicine designed to reduce angiopoietin-like 3 protein, or ANGPTL3.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="VupanorsenMember" xlink:to="ions_VupanorsenMember_lbl" xlink:title="label: VupanorsenMember to ions_VupanorsenMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_VupanorsenMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_VupanorsenMember_lbl1" xml:lang="en-US" id="ions_VupanorsenMember_lbl1">Vupanorsen [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="VupanorsenMember" xlink:to="ions_VupanorsenMember_lbl1" xlink:title="label: VupanorsenMember to ions_VupanorsenMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_VupanorsenMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_VupanorsenMember_lbl2" xml:lang="en-US" id="ions_VupanorsenMember_lbl2">Vupanorsen [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="VupanorsenMember" xlink:to="ions_VupanorsenMember_lbl2" xlink:title="label: VupanorsenMember to ions_VupanorsenMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20201231.xsd#ions_VupanorsenActivePharmaceuticalIngredientMember" xlink:label="VupanorsenActivePharmaceuticalIngredientMember" xlink:title="VupanorsenActivePharmaceuticalIngredientMember" />
    <link:label xlink:type="resource" xlink:label="ions_VupanorsenActivePharmaceuticalIngredientMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_VupanorsenActivePharmaceuticalIngredientMember_lbl" xml:lang="en-US" id="ions_VupanorsenActivePharmaceuticalIngredientMember_lbl">The active pharmaceutical ingredient, or API, for Vupanorsen, a ligand-conjugated (LICA) investigational antisense medicine designed to reduce angiopoietin-like 3 protein, or ANGPTL3.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="VupanorsenActivePharmaceuticalIngredientMember" xlink:to="ions_VupanorsenActivePharmaceuticalIngredientMember_lbl" xlink:title="label: VupanorsenActivePharmaceuticalIngredientMember to ions_VupanorsenActivePharmaceuticalIngredientMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_VupanorsenActivePharmaceuticalIngredientMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_VupanorsenActivePharmaceuticalIngredientMember_lbl1" xml:lang="en-US" id="ions_VupanorsenActivePharmaceuticalIngredientMember_lbl1">Vupanorsen Active Pharmaceutical Ingredient [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="VupanorsenActivePharmaceuticalIngredientMember" xlink:to="ions_VupanorsenActivePharmaceuticalIngredientMember_lbl1" xlink:title="label: VupanorsenActivePharmaceuticalIngredientMember to ions_VupanorsenActivePharmaceuticalIngredientMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_VupanorsenActivePharmaceuticalIngredientMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_VupanorsenActivePharmaceuticalIngredientMember_lbl2" xml:lang="en-US" id="ions_VupanorsenActivePharmaceuticalIngredientMember_lbl2">Vupanorsen API [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="VupanorsenActivePharmaceuticalIngredientMember" xlink:to="ions_VupanorsenActivePharmaceuticalIngredientMember_lbl2" xlink:title="label: VupanorsenActivePharmaceuticalIngredientMember to ions_VupanorsenActivePharmaceuticalIngredientMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20201231.xsd#ions_MaximumAmountOfPaymentsReceivableForDevelopmentMilestones" xlink:label="MaximumAmountOfPaymentsReceivableForDevelopmentMilestones" xlink:title="MaximumAmountOfPaymentsReceivableForDevelopmentMilestones" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfPaymentsReceivableForDevelopmentMilestones_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_MaximumAmountOfPaymentsReceivableForDevelopmentMilestones_lbl" xml:lang="en-US" id="ions_MaximumAmountOfPaymentsReceivableForDevelopmentMilestones_lbl">The maximum amount of payments receivable for development milestones under the collaboration agreement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfPaymentsReceivableForDevelopmentMilestones" xlink:to="ions_MaximumAmountOfPaymentsReceivableForDevelopmentMilestones_lbl" xlink:title="label: MaximumAmountOfPaymentsReceivableForDevelopmentMilestones to ions_MaximumAmountOfPaymentsReceivableForDevelopmentMilestones_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfPaymentsReceivableForDevelopmentMilestones_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_MaximumAmountOfPaymentsReceivableForDevelopmentMilestones_lbl1" xml:lang="en-US" id="ions_MaximumAmountOfPaymentsReceivableForDevelopmentMilestones_lbl1">Maximum amount of payments receivable for development milestones</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfPaymentsReceivableForDevelopmentMilestones" xlink:to="ions_MaximumAmountOfPaymentsReceivableForDevelopmentMilestones_lbl1" xlink:title="label: MaximumAmountOfPaymentsReceivableForDevelopmentMilestones to ions_MaximumAmountOfPaymentsReceivableForDevelopmentMilestones_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfPaymentsReceivableForDevelopmentMilestones_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_MaximumAmountOfPaymentsReceivableForDevelopmentMilestones_lbl2" xml:lang="en-US" id="ions_MaximumAmountOfPaymentsReceivableForDevelopmentMilestones_lbl2">Maximum amount of payments receivable for development milestones</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfPaymentsReceivableForDevelopmentMilestones" xlink:to="ions_MaximumAmountOfPaymentsReceivableForDevelopmentMilestones_lbl2" xlink:title="label: MaximumAmountOfPaymentsReceivableForDevelopmentMilestones to ions_MaximumAmountOfPaymentsReceivableForDevelopmentMilestones_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20201231.xsd#ions_RoyaltyPercentageReceivedOnNetSalesOfDrug" xlink:label="RoyaltyPercentageReceivedOnNetSalesOfDrug" xlink:title="RoyaltyPercentageReceivedOnNetSalesOfDrug" />
    <link:label xlink:type="resource" xlink:label="ions_RoyaltyPercentageReceivedOnNetSalesOfDrug_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_RoyaltyPercentageReceivedOnNetSalesOfDrug_lbl" xml:lang="en-US" id="ions_RoyaltyPercentageReceivedOnNetSalesOfDrug_lbl">Royalty percentage received on the net sales of a drug 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="RoyaltyPercentageReceivedOnNetSalesOfDrug" xlink:to="ions_RoyaltyPercentageReceivedOnNetSalesOfDrug_lbl" xlink:title="label: RoyaltyPercentageReceivedOnNetSalesOfDrug to ions_RoyaltyPercentageReceivedOnNetSalesOfDrug_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_RoyaltyPercentageReceivedOnNetSalesOfDrug_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_RoyaltyPercentageReceivedOnNetSalesOfDrug_lbl1" xml:lang="en-US" id="ions_RoyaltyPercentageReceivedOnNetSalesOfDrug_lbl1">Royalty percentage received on net sales of drug</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RoyaltyPercentageReceivedOnNetSalesOfDrug" xlink:to="ions_RoyaltyPercentageReceivedOnNetSalesOfDrug_lbl1" xlink:title="label: RoyaltyPercentageReceivedOnNetSalesOfDrug to ions_RoyaltyPercentageReceivedOnNetSalesOfDrug_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_RoyaltyPercentageReceivedOnNetSalesOfDrug_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_RoyaltyPercentageReceivedOnNetSalesOfDrug_lbl2" xml:lang="en-US" id="ions_RoyaltyPercentageReceivedOnNetSalesOfDrug_lbl2">Royalty percentage received on net sales of drug</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RoyaltyPercentageReceivedOnNetSalesOfDrug" xlink:to="ions_RoyaltyPercentageReceivedOnNetSalesOfDrug_lbl2" xlink:title="label: RoyaltyPercentageReceivedOnNetSalesOfDrug to ions_RoyaltyPercentageReceivedOnNetSalesOfDrug_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20201231.xsd#ions_MaximumAmountOfPaymentsReceivableForDevelopmentRegulatoryAndSalesMilestones" xlink:label="MaximumAmountOfPaymentsReceivableForDevelopmentRegulatoryAndSalesMilestones" xlink:title="MaximumAmountOfPaymentsReceivableForDevelopmentRegulatoryAndSalesMilestones" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfPaymentsReceivableForDevelopmentRegulatoryAndSalesMilestones_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_MaximumAmountOfPaymentsReceivableForDevelopmentRegulatoryAndSalesMilestones_lbl" xml:lang="en-US" id="ions_MaximumAmountOfPaymentsReceivableForDevelopmentRegulatoryAndSalesMilestones_lbl">The maximum amount of payments receivable for development, regulatory and sales milestones under the collaboration agreement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfPaymentsReceivableForDevelopmentRegulatoryAndSalesMilestones" xlink:to="ions_MaximumAmountOfPaymentsReceivableForDevelopmentRegulatoryAndSalesMilestones_lbl" xlink:title="label: MaximumAmountOfPaymentsReceivableForDevelopmentRegulatoryAndSalesMilestones to ions_MaximumAmountOfPaymentsReceivableForDevelopmentRegulatoryAndSalesMilestones_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfPaymentsReceivableForDevelopmentRegulatoryAndSalesMilestones_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_MaximumAmountOfPaymentsReceivableForDevelopmentRegulatoryAndSalesMilestones_lbl1" xml:lang="en-US" id="ions_MaximumAmountOfPaymentsReceivableForDevelopmentRegulatoryAndSalesMilestones_lbl1">Maximum amount of payments receivable for development, regulatory and sales milestones</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfPaymentsReceivableForDevelopmentRegulatoryAndSalesMilestones" xlink:to="ions_MaximumAmountOfPaymentsReceivableForDevelopmentRegulatoryAndSalesMilestones_lbl1" xlink:title="label: MaximumAmountOfPaymentsReceivableForDevelopmentRegulatoryAndSalesMilestones to ions_MaximumAmountOfPaymentsReceivableForDevelopmentRegulatoryAndSalesMilestones_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfPaymentsReceivableForDevelopmentRegulatoryAndSalesMilestones_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_MaximumAmountOfPaymentsReceivableForDevelopmentRegulatoryAndSalesMilestones_lbl2" xml:lang="en-US" id="ions_MaximumAmountOfPaymentsReceivableForDevelopmentRegulatoryAndSalesMilestones_lbl2">Maximum amount of payments receivable for development, regulatory and sales milestones</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfPaymentsReceivableForDevelopmentRegulatoryAndSalesMilestones" xlink:to="ions_MaximumAmountOfPaymentsReceivableForDevelopmentRegulatoryAndSalesMilestones_lbl2" xlink:title="label: MaximumAmountOfPaymentsReceivableForDevelopmentRegulatoryAndSalesMilestones to ions_MaximumAmountOfPaymentsReceivableForDevelopmentRegulatoryAndSalesMilestones_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20201231.xsd#ions_CollaborativeArrangementAndLicensingAgreementAbstract" xlink:label="CollaborativeArrangementAndLicensingAgreementAbstract" xlink:title="CollaborativeArrangementAndLicensingAgreementAbstract" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementAndLicensingAgreementAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_CollaborativeArrangementAndLicensingAgreementAbstract_lbl1" xml:lang="en-US" id="ions_CollaborativeArrangementAndLicensingAgreementAbstract_lbl1">Collaborative Arrangement and Licensing Agreement [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementAndLicensingAgreementAbstract" xlink:to="ions_CollaborativeArrangementAndLicensingAgreementAbstract_lbl1" xlink:title="label: CollaborativeArrangementAndLicensingAgreementAbstract to ions_CollaborativeArrangementAndLicensingAgreementAbstract_lbl1" />
    <link:loc xlink:type="locator" xlink:href="ions-20201231.xsd#ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2019WithPfizerMember" xlink:label="CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2019WithPfizerMember" xlink:title="CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2019WithPfizerMember" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2019WithPfizerMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2019WithPfizerMember_lbl" xml:lang="en-US" id="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2019WithPfizerMember_lbl">Represents information pertaining to the collaborative arrangements and licensing agreements entered into with Pfizer for the license of AKCEA-ANGPTL3-LR to treat people with cardiovascular and metabolic diseases..</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2019WithPfizerMember" xlink:to="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2019WithPfizerMember_lbl" xlink:title="label: CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2019WithPfizerMember to ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2019WithPfizerMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2019WithPfizerMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2019WithPfizerMember_lbl1" xml:lang="en-US" id="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2019WithPfizerMember_lbl1">Collaborative Arrangement and Licensing Agreement Entered Into in October 2019 with Pfizer [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2019WithPfizerMember" xlink:to="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2019WithPfizerMember_lbl1" xlink:title="label: CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2019WithPfizerMember to ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2019WithPfizerMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2019WithPfizerMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2019WithPfizerMember_lbl2" xml:lang="en-US" id="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2019WithPfizerMember_lbl2">Pfizer [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2019WithPfizerMember" xlink:to="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2019WithPfizerMember_lbl2" xlink:title="label: CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2019WithPfizerMember to ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2019WithPfizerMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20201231.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 and lease obligation, 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">Long-term obligations, less current portion</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-20201231.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, excluding convertible debt, and lease obligations, classified as current, and other current liabilities.</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/2003/role/terseLabel" xlink:title="ions_LongTermObligationsCurrent_lbl2" xml:lang="en-US" id="ions_LongTermObligationsCurrent_lbl2">Current portion of long-term obligations</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-20201231.xsd#ions_LesseeOperatingLeaseInitialLetterOfCreditToSecureLeaseObligation" xlink:label="LesseeOperatingLeaseInitialLetterOfCreditToSecureLeaseObligation" xlink:title="LesseeOperatingLeaseInitialLetterOfCreditToSecureLeaseObligation" />
    <link:label xlink:type="resource" xlink:label="ions_LesseeOperatingLeaseInitialLetterOfCreditToSecureLeaseObligation_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_LesseeOperatingLeaseInitialLetterOfCreditToSecureLeaseObligation_lbl" xml:lang="en-US" id="ions_LesseeOperatingLeaseInitialLetterOfCreditToSecureLeaseObligation_lbl">Initial letter of credit provided to lessor to secure lease obligation under lessee's operating lease.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeOperatingLeaseInitialLetterOfCreditToSecureLeaseObligation" xlink:to="ions_LesseeOperatingLeaseInitialLetterOfCreditToSecureLeaseObligation_lbl" xlink:title="label: LesseeOperatingLeaseInitialLetterOfCreditToSecureLeaseObligation to ions_LesseeOperatingLeaseInitialLetterOfCreditToSecureLeaseObligation_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_LesseeOperatingLeaseInitialLetterOfCreditToSecureLeaseObligation_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_LesseeOperatingLeaseInitialLetterOfCreditToSecureLeaseObligation_lbl1" xml:lang="en-US" id="ions_LesseeOperatingLeaseInitialLetterOfCreditToSecureLeaseObligation_lbl1">Lessee, Operating Lease, Initial Letter of Credit to Secure Lease Obligation</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeOperatingLeaseInitialLetterOfCreditToSecureLeaseObligation" xlink:to="ions_LesseeOperatingLeaseInitialLetterOfCreditToSecureLeaseObligation_lbl1" xlink:title="label: LesseeOperatingLeaseInitialLetterOfCreditToSecureLeaseObligation to ions_LesseeOperatingLeaseInitialLetterOfCreditToSecureLeaseObligation_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_LesseeOperatingLeaseInitialLetterOfCreditToSecureLeaseObligation_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_LesseeOperatingLeaseInitialLetterOfCreditToSecureLeaseObligation_lbl2" xml:lang="en-US" id="ions_LesseeOperatingLeaseInitialLetterOfCreditToSecureLeaseObligation_lbl2">Initial amount of letter of credit</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeOperatingLeaseInitialLetterOfCreditToSecureLeaseObligation" xlink:to="ions_LesseeOperatingLeaseInitialLetterOfCreditToSecureLeaseObligation_lbl2" xlink:title="label: LesseeOperatingLeaseInitialLetterOfCreditToSecureLeaseObligation to ions_LesseeOperatingLeaseInitialLetterOfCreditToSecureLeaseObligation_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20201231.xsd#ions_LesseeLeasingArrangementsOperatingLeasesNumberOfOptionsToExtendLease" xlink:label="LesseeLeasingArrangementsOperatingLeasesNumberOfOptionsToExtendLease" xlink:title="LesseeLeasingArrangementsOperatingLeasesNumberOfOptionsToExtendLease" />
    <link:label xlink:type="resource" xlink:label="ions_LesseeLeasingArrangementsOperatingLeasesNumberOfOptionsToExtendLease_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_LesseeLeasingArrangementsOperatingLeasesNumberOfOptionsToExtendLease_lbl" xml:lang="en-US" id="ions_LesseeLeasingArrangementsOperatingLeasesNumberOfOptionsToExtendLease_lbl">The number of options to extend the lease under the lessee's operating leasing arrangement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeLeasingArrangementsOperatingLeasesNumberOfOptionsToExtendLease" xlink:to="ions_LesseeLeasingArrangementsOperatingLeasesNumberOfOptionsToExtendLease_lbl" xlink:title="label: LesseeLeasingArrangementsOperatingLeasesNumberOfOptionsToExtendLease to ions_LesseeLeasingArrangementsOperatingLeasesNumberOfOptionsToExtendLease_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_LesseeLeasingArrangementsOperatingLeasesNumberOfOptionsToExtendLease_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_LesseeLeasingArrangementsOperatingLeasesNumberOfOptionsToExtendLease_lbl1" xml:lang="en-US" id="ions_LesseeLeasingArrangementsOperatingLeasesNumberOfOptionsToExtendLease_lbl1">Lessee, Leasing Arrangements, Operating Leases, 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="LesseeLeasingArrangementsOperatingLeasesNumberOfOptionsToExtendLease" xlink:to="ions_LesseeLeasingArrangementsOperatingLeasesNumberOfOptionsToExtendLease_lbl1" xlink:title="label: LesseeLeasingArrangementsOperatingLeasesNumberOfOptionsToExtendLease to ions_LesseeLeasingArrangementsOperatingLeasesNumberOfOptionsToExtendLease_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_LesseeLeasingArrangementsOperatingLeasesNumberOfOptionsToExtendLease_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_LesseeLeasingArrangementsOperatingLeasesNumberOfOptionsToExtendLease_lbl2" xml:lang="en-US" id="ions_LesseeLeasingArrangementsOperatingLeasesNumberOfOptionsToExtendLease_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="LesseeLeasingArrangementsOperatingLeasesNumberOfOptionsToExtendLease" xlink:to="ions_LesseeLeasingArrangementsOperatingLeasesNumberOfOptionsToExtendLease_lbl2" xlink:title="label: LesseeLeasingArrangementsOperatingLeasesNumberOfOptionsToExtendLease to ions_LesseeLeasingArrangementsOperatingLeasesNumberOfOptionsToExtendLease_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20201231.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-20201231.xsd#ions_LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnThirdAnniversaryOfRentCommencementDate" xlink:label="LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnThirdAnniversaryOfRentCommencementDate" xlink:title="LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnThirdAnniversaryOfRentCommencementDate" />
    <link:label xlink:type="resource" xlink:label="ions_LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnThirdAnniversaryOfRentCommencementDate_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnThirdAnniversaryOfRentCommencementDate_lbl" xml:lang="en-US" id="ions_LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnThirdAnniversaryOfRentCommencementDate_lbl">Letter of credit provided to lessor to secure lease obligation under lessee's operating lease on the third anniversary of the rent commencement date.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnThirdAnniversaryOfRentCommencementDate" xlink:to="ions_LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnThirdAnniversaryOfRentCommencementDate_lbl" xlink:title="label: LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnThirdAnniversaryOfRentCommencementDate to ions_LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnThirdAnniversaryOfRentCommencementDate_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnThirdAnniversaryOfRentCommencementDate_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnThirdAnniversaryOfRentCommencementDate_lbl1" xml:lang="en-US" id="ions_LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnThirdAnniversaryOfRentCommencementDate_lbl1">Lessee, Operating Lease, Letter of Credit to Secure Lease Obligation on Third Anniversary of Rent Commencement Date</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnThirdAnniversaryOfRentCommencementDate" xlink:to="ions_LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnThirdAnniversaryOfRentCommencementDate_lbl1" xlink:title="label: LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnThirdAnniversaryOfRentCommencementDate to ions_LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnThirdAnniversaryOfRentCommencementDate_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnThirdAnniversaryOfRentCommencementDate_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnThirdAnniversaryOfRentCommencementDate_lbl2" xml:lang="en-US" id="ions_LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnThirdAnniversaryOfRentCommencementDate_lbl2">Letter of credit on third anniversary of rent commencement date</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnThirdAnniversaryOfRentCommencementDate" xlink:to="ions_LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnThirdAnniversaryOfRentCommencementDate_lbl2" xlink:title="label: LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnThirdAnniversaryOfRentCommencementDate to ions_LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnThirdAnniversaryOfRentCommencementDate_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20201231.xsd#ions_LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnFifthAnniversaryOfRentCommencementDate" xlink:label="LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnFifthAnniversaryOfRentCommencementDate" xlink:title="LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnFifthAnniversaryOfRentCommencementDate" />
    <link:label xlink:type="resource" xlink:label="ions_LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnFifthAnniversaryOfRentCommencementDate_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnFifthAnniversaryOfRentCommencementDate_lbl" xml:lang="en-US" id="ions_LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnFifthAnniversaryOfRentCommencementDate_lbl">Letter of credit provided to lessor to secure lease obligation under lessee's operating lease on the fifth anniversary of the rent commencement date.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnFifthAnniversaryOfRentCommencementDate" xlink:to="ions_LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnFifthAnniversaryOfRentCommencementDate_lbl" xlink:title="label: LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnFifthAnniversaryOfRentCommencementDate to ions_LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnFifthAnniversaryOfRentCommencementDate_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnFifthAnniversaryOfRentCommencementDate_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnFifthAnniversaryOfRentCommencementDate_lbl1" xml:lang="en-US" id="ions_LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnFifthAnniversaryOfRentCommencementDate_lbl1">Lessee, Operating Lease, Letter of Credit to Secure Lease Obligation on Fifth Anniversary of Rent Commencement Date</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnFifthAnniversaryOfRentCommencementDate" xlink:to="ions_LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnFifthAnniversaryOfRentCommencementDate_lbl1" xlink:title="label: LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnFifthAnniversaryOfRentCommencementDate to ions_LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnFifthAnniversaryOfRentCommencementDate_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnFifthAnniversaryOfRentCommencementDate_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnFifthAnniversaryOfRentCommencementDate_lbl2" xml:lang="en-US" id="ions_LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnFifthAnniversaryOfRentCommencementDate_lbl2">Letter of credit on fifth anniversary of rent commencement date</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnFifthAnniversaryOfRentCommencementDate" xlink:to="ions_LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnFifthAnniversaryOfRentCommencementDate_lbl2" xlink:title="label: LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnFifthAnniversaryOfRentCommencementDate to ions_LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnFifthAnniversaryOfRentCommencementDate_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20201231.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.</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-20201231.xsd#ions_LesseeOperatingLeaseAllowanceForTenantImprovements" xlink:label="LesseeOperatingLeaseAllowanceForTenantImprovements" xlink:title="LesseeOperatingLeaseAllowanceForTenantImprovements" />
    <link:label xlink:type="resource" xlink:label="ions_LesseeOperatingLeaseAllowanceForTenantImprovements_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_LesseeOperatingLeaseAllowanceForTenantImprovements_lbl" xml:lang="en-US" id="ions_LesseeOperatingLeaseAllowanceForTenantImprovements_lbl">Allowance for tenant improvements to the office space included in the lessee's operating lease.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeOperatingLeaseAllowanceForTenantImprovements" xlink:to="ions_LesseeOperatingLeaseAllowanceForTenantImprovements_lbl" xlink:title="label: LesseeOperatingLeaseAllowanceForTenantImprovements to ions_LesseeOperatingLeaseAllowanceForTenantImprovements_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_LesseeOperatingLeaseAllowanceForTenantImprovements_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_LesseeOperatingLeaseAllowanceForTenantImprovements_lbl1" xml:lang="en-US" id="ions_LesseeOperatingLeaseAllowanceForTenantImprovements_lbl1">Lessee, Operating Lease, Allowance for Tenant Improvements</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeOperatingLeaseAllowanceForTenantImprovements" xlink:to="ions_LesseeOperatingLeaseAllowanceForTenantImprovements_lbl1" xlink:title="label: LesseeOperatingLeaseAllowanceForTenantImprovements to ions_LesseeOperatingLeaseAllowanceForTenantImprovements_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_LesseeOperatingLeaseAllowanceForTenantImprovements_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_LesseeOperatingLeaseAllowanceForTenantImprovements_lbl2" xml:lang="en-US" id="ions_LesseeOperatingLeaseAllowanceForTenantImprovements_lbl2">Tenant improvement allowance</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeOperatingLeaseAllowanceForTenantImprovements" xlink:to="ions_LesseeOperatingLeaseAllowanceForTenantImprovements_lbl2" xlink:title="label: LesseeOperatingLeaseAllowanceForTenantImprovements to ions_LesseeOperatingLeaseAllowanceForTenantImprovements_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20201231.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-20201231.xsd#ions_CarlsbadOfficeSpacesMember" xlink:label="CarlsbadOfficeSpacesMember" xlink:title="CarlsbadOfficeSpacesMember" />
    <link:label xlink:type="resource" xlink:label="ions_CarlsbadOfficeSpacesMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_CarlsbadOfficeSpacesMember_lbl" xml:lang="en-US" id="ions_CarlsbadOfficeSpacesMember_lbl">Additional office spaces in Carlsbad, California leased under non-cancelable operating lease.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CarlsbadOfficeSpacesMember" xlink:to="ions_CarlsbadOfficeSpacesMember_lbl" xlink:title="label: CarlsbadOfficeSpacesMember to ions_CarlsbadOfficeSpacesMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_CarlsbadOfficeSpacesMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_CarlsbadOfficeSpacesMember_lbl1" xml:lang="en-US" id="ions_CarlsbadOfficeSpacesMember_lbl1">Carlsbad Office Spaces [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CarlsbadOfficeSpacesMember" xlink:to="ions_CarlsbadOfficeSpacesMember_lbl1" xlink:title="label: CarlsbadOfficeSpacesMember to ions_CarlsbadOfficeSpacesMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_CarlsbadOfficeSpacesMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_CarlsbadOfficeSpacesMember_lbl2" xml:lang="en-US" id="ions_CarlsbadOfficeSpacesMember_lbl2">Carlsbad Office Spaces [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CarlsbadOfficeSpacesMember" xlink:to="ions_CarlsbadOfficeSpacesMember_lbl2" xlink:title="label: CarlsbadOfficeSpacesMember to ions_CarlsbadOfficeSpacesMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20201231.xsd#ions_AkceaTherapeuticsIncMember" xlink:label="AkceaTherapeuticsIncMember" xlink:title="AkceaTherapeuticsIncMember" />
    <link:label xlink:type="resource" xlink:label="ions_AkceaTherapeuticsIncMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_AkceaTherapeuticsIncMember_lbl" xml:lang="en-US" id="ions_AkceaTherapeuticsIncMember_lbl">Akcea Therapeutics, Inc. is a subsidiary of the Company and was formed to develop and commercialize drugs for cardiometabolic disorders.</link:label>
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<DESCRIPTION>XBRL TAXONOMY EXTENSION PRESENTATION LINKBASE
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M7^X:/(E_N&@>G<CHJ3R)?[AH\B7^X:"N9$=%2>1+_<-'D2_W#0',B.BI/(E_
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MR*V[+,P.<GK_ $JWXG\,6?BJPAM;NXN[9H)UN(9[.7RY8W7."IP?4]JW_(E_
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M P03P1CI72>1+_<-'D2_W#0*\3A=/^%^CVE]:W-WJ.LZJMFP:UM]2O#+# PZ
M%5P.GOFNAM- M;+Q%J6MQR3&YU".*.5&8;%$8(&T8SWYR36SY$O]PT>1+_<-
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M+>TCO(Y=Y';JS,>236G4GD2_W#1Y$O\ <- 71'14GD2_W#1Y$O\ <- ^9$=%
M2>1+_<-'D2_W#0',B.BI/(E_N&CR)?[AH#F1'14GD2_W#1Y$O]PT!S(CHJ3R
M)?[AH\B7^X: YD1T5)Y$O]PT>1+_ '#0',B.BI/(E_N&CR)?[AH#F1'14GD2
M_P!PT>1+_<- <R(Z\T^+?_,'_P"VW_LE>G^1+_<-<+\1_#FKZU_9G]G63S^5
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M83_GXCA:*[K_ (5-XC_OV/\ W^/_ ,31_P *F\1_W['_ +_'_P")HYD']I83
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MH **** "BBB@ HHHH **** "BBB@ HHHH **** "BBB@ HHHH **** "BBB@
M HHHH **** "BBB@ HHHH **** "BBB@ HHHH **** "BBB@ HHHH **** "
MBBB@ HHHH **** "BBB@ HHHH **** "BBB@ HHHH **** "BBB@ HHHH **
M** (///H*///H*BHK#G9MRHE\\^@H\\^@K+U#7-(TAXTU+5;&R:3[BW-PD9;
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MT%'GGT%144<[#E1+YY]!1YY]!45%'.PY42^>?04>>?05%11SL.5$OGGT%'GG
MT%144<[#E1+YY]!1YY]!45%'.PY42^>?04>>?05%11SL.5$OGGT%'GGT%144
M<[#E1+YY]!1YY]!45%'.PY42^>?04>>?05%11SL.5$OGGT%'GGT%144<[#E1
M+YY]!1YY]!45%'.PY42^>?04>>?05%11SL.5$OGGT%'GGT%144<[#E1+YY]!
M1YY]!45%'.PY42^>?04>>?05%11SL.5$OGGT%'GGT%144<[#E1+YY]!1YY]!
M45%'.PY42^>?04>>?05%11SL.5$OGGT%'GGT%144<[#E1+YY]!1YY]!45%'.
MPY42^>?04>>?05%11SL.5$OGGT%'GGT%144<[#E1+YY]!1YY]!45%'.PY42^
M>?04>>?05%11SL.5$OGGT%'GGT%144<[#E1+YY]!1YY]!45%'.PY42^>?04>
M>?05%11SL.5$OGGT%'GGT%144<[#E1+YY]!1YY]!45%'.PY42^>?04>>?05%
M11SL.5$OGGT%'GGT%144<[#E1+YY]!1YY]!45%'.PY42^>?04>>?05%11SL.
M5$OGGT%'GGT%144<[#E1+YY]!1YY]!45%'.PY42^>?04>>?05%11SL.5$OGG
MT%'GGT%144<[#E1+YY]!1YY]!45%'.PY42^>?04>>?05%11SL.5$OGGT%'GG
MT%144<[#E1+YY]!1YY]!45%'.PY42^>?04>>?05%11SL.5$OGGT%'GGT%144
M<[#E1+YY]!1YY]!45%'.PY42^>?04>>?05%11SL.5$OGGT%'GGT%144<[#E1
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MV*44D34445J9!1110 4444 %%%% !1110 4444 %%%% !1110 4444 %%%%
M!1110 4444 %%%% !1110 4444 %%%% !1110 4444 %%%% !1110 4444 %
M%%% !1110 4444 %%%% !1110 4444 %%%% !1110 4444 %%%% !1110 44
M44 %%%% !1110 4444 %%%% !1110 4444 %%%% !1110 4444 %%%% !111
M0 4444 %%%% !1110 4444 %%%% !1110 4444 %%%% !1110 4444 %%%%
M!1110 4444 %%%% !1110 4444 %%%% !1110!3IKL$1G/11FG4A (((R#P1
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<DOCUMENT>
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<DOCUMENT>
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<SEQUENCE>32
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&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;1. Organization and Significant Accounting Policies&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Basis of Presentation&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;In our consolidated financial statements we included the accounts of Ionis Pharmaceuticals, Inc. and the consolidated results of our subsidiary, Akcea Therapeutics, Inc. and its wholly owned subsidiaries (&#x201c;we&#x201d;, &#x201c;us&#x201d; or &#x201c;our&#x201d;). We formed Akcea in December 2014. In July 2017, Akcea completed an initial public offering, or IPO. Prior to Akcea&#x2019;s IPO in July 2017, we owned &lt;/span&gt;100 percent&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; of Akcea. In October 2020, we acquired the shares of Akcea&#x2019;s common stock we did not own. We will refer to this transaction as the Akcea Acquisition throughout the remainder of this document. &lt;/span&gt;See Note 7, &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Akcea Acquisition&lt;/span&gt;, in the Notes to the Consolidated Financial Statements for further details.&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; We reflected changes in our ownership percentage in our financial statements as an adjustment to noncontrolling interest in the period the change occurred.&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Organization and Business Activity&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; &lt;/span&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We incorporated in California on January 10, 1989. In conjunction with our IPO, we reorganized as a Delaware corporation in April 1991. We were organized principally to develop human therapeutic medicines using antisense technology. In December 2015, we changed our name from Isis Pharmaceuticals, Inc. to Ionis Pharmaceuticals, Inc.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Basic and Diluted Net Income (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 income (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 income (loss) per share by dividing the total net income (loss) attributable to our common stockholders 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;"&gt;The calculation of total net income (loss) attributable to our common stockholders for each year considered our net income (loss) for Ionis on a stand-alone basis plus our share of Akcea&#x2019;s net income (loss) for the period. To calculate the portion of Akcea&#x2019;s net income (loss) attributable to our ownership for each year, we multiplied Akcea&#x2019;s income (loss) per share by the weighted average shares we owned in Akcea during the period. As a result of this calculation, our total net income (loss) available to Ionis common stockholders for the calculation of net income (loss) per share is different than net income (loss) attributable to Ionis Pharmaceuticals, Inc. common stockholders in our consolidated statements of operations for each 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;"&gt;Our basic net income (loss) per share was calculated as follows (in thousands, except per share amounts):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" id="z52a07e9978cc42e1b09d31421865a2e3" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; border-bottom: #000000 2px solid; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Year Ended December 31, 2020&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Weighted&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Average Shares&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Owned in Akcea&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Akcea&lt;/span&gt;&#x2019;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;s&lt;/span&gt;&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Net Loss&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Per Share&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Basic Net Loss&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Per Share&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Calculation&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Akcea&#x2019;s net loss in the pre-acquisition period attributable to our ownership&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;77,095&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(1.45&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(111,775&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Akcea&#x2019;s net loss in the post-acquisition period attributable to our ownership&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(85,987&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Akcea&#x2019;s total net loss attributable to our ownership&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(197,762&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Ionis&#x2019; stand-alone net loss&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(253,725&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Net loss available to Ionis common stockholders&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(451,487&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Weighted average shares outstanding&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;139,612&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Basic net loss per share&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(3.23&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&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" id="z7190f4cfc9904c35afaf55ca55271bf2" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; border-bottom: #000000 2px solid; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Year Ended December 31, 2019&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Weighted&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Average Shares&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Owned in Akcea&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Akcea&lt;/span&gt;&#x2019;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;s&lt;/span&gt;&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Net Income&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Per Share&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Basic Net Income&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Per Share&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Calculation&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Common shares&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;70,100&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.49&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;34,073&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Akcea&#x2019;s net income attributable to our ownership&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;&#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%; 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;&#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%; 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;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&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;34,073&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Ionis&#x2019; stand-alone net income&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;262,490&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;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Net income available to Ionis common stockholders&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 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; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;296,563&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Weighted average shares outstanding&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;139,998&lt;/div&gt;&lt;/td&gt;
    &lt;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: top; width: 64%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Basic net income per share&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2.12&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" id="zc4df006abbbb4d5b9a0a303fb389d2b3" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; border-bottom: #000000 2px solid; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Year Ended December 31, 2018&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Weighted&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Average Shares&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Owned in Akcea&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Akcea&lt;/span&gt;&#x2019;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;s&lt;/span&gt;&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Net Loss&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Per Share&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Basic Net Income&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Per Share&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Calculation&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Common shares&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;59,812&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(2.74&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;(163,938&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Akcea&#x2019;s net loss attributable to our ownership&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;&#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%; 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;&#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%; 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;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&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;(163,938&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Ionis&#x2019; stand-alone net income&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;440,806&lt;/div&gt;&lt;/td&gt;
    &lt;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: top; width: 64%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Net income available to Ionis common stockholders&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 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; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;276,868&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Weighted average shares outstanding&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;132,320&lt;/div&gt;&lt;/td&gt;
    &lt;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: top; width: 64%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Basic net income per share&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2.09&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; font-style: italic;"&gt;Diluted net income 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 year ended December 31, 2020, we incurred a net loss; therefore, we did not include dilutive common equivalent shares in the computation of diluted net loss per share because the effect would have been anti-dilutive. Common stock 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" id="za661525f8bef42ea9eb273beec8c3ffa" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; 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;&lt;/span&gt;&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="zcb135ba690824483aa0fa909f89a6a2a" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1 percent&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; convertible senior notes;&lt;/span&gt;&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="zd9638f50b7c74568a481c388188fcd9b" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; 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" id="zbac81e814d3144cfb944e6b840054211" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; 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; and&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="za8f44a91052a49768a8cab1258c98733" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; 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;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;For the years ended December 31, 2019 and 2018, we had net income available to Ionis common stockholders. As a result, we computed diluted net income per share using the weighted-average number of common shares and dilutive common equivalent shares outstanding during each period.&lt;/span&gt; We calculated our diluted net income per share as follows &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;(in thousands except per share amounts):&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" id="zbebb8966d0bf411b9c7f046d05640cb2" 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;Year Ended December 31, 2019&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Income&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;(Numerator)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Shares&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;(Denominator)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Per-Share&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Amount&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Net income available to Ionis common stockholders&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;296,563&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;139,998&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;2.12&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Effect of dilutive securities:&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -8.9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Shares issuable upon exercise of stock options&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2,090&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: 0.1pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Shares issuable upon restricted stock award issuance&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;766&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Shares issuable related to our ESPP&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #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;18&lt;/div&gt;&lt;/td&gt;
    &lt;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%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 4px;" 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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;296,563&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;142,872&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;2.08&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" id="zd2aad674b25d40a39b5785fe82a18973" 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;Year Ended December 31, 2018&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Income&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;(Numerator)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Shares&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;(Denominator)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Per-Share&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Amount&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Net income available to Ionis common stockholders&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;276,868&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;132,320&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;2.09&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Effect of dilutive securities:&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -8.9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Shares issuable upon exercise of stock options&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,216&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: 0.1pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Shares issuable upon restricted stock award issuance&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;514&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Shares issuable related to our ESPP&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #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;6&lt;/div&gt;&lt;/td&gt;
    &lt;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%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 4px;" 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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;276,868&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;134,056&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;2.07&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 each year presented, the calculation excluded our convertible senior notes because the effect on diluted earnings per share was anti-dilutive.&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;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;&lt;span style="text-decoration: underline;"&gt;Our Revenue Sources&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 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 in deferred revenue on our consolidated balance sheet.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;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;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 will also recognize as commercial revenue sales milestone payments and royalties we earn under our other partnerships.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;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;Commercial Revenue: Product sales, 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 added product sales from TEGSEDI to our commercial revenue in the fourth quarter of 2018 and we added product sales from WAYLIVRA to our commercial revenue in the third quarter of 2019. &lt;/span&gt;In the U.S., we distribute TEGSEDI through an exclusive distribution agreement with a third-party logistics company, or 3PL, that takes title to TEGSEDI. The 3PL is our sole customer in the U.S. The 3PL then distributes TEGSEDI to a specialty pharmacy and a specialty distributor, which we collectively refer to as wholesalers, who then distribute TEGSEDI to health care providers and patients.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&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 Europe, through 2020 we sold TEGSEDI and WAYLIVRA to hospitals and pharmacies using 3PLs as distributors. Beginning in 2021, we are commercializing TEGSEDI and WAYLIVRA in Europe through a distribution agreement with Swedish Orphan Biovitrum AB, or Sobi, an international biopharmaceutical company that focuses on rare diseases. Under the terms of this agreement, we retained the marketing authorization for both medicines in Europe.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&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 Latin America beginning in 2020, we sold TEGSEDI and WAYLIVRA to our partner, PTC Therapeutics. Under our collaboration agreement with PTC, PTC is commercializing TEGSEDI and WAYLIVRA in Latin America and Caribbean countries.&lt;/div&gt;

&lt;div&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 collaborative 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 often 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, research and development, or R&amp;amp;D, services, and manufacturing services.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We provide details about our collaboration agreements in Note 6, &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;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;&#160;&lt;/span&gt;Under each collaboration note we discuss our specific revenue recognition conclusions, including our significant performance obligations under each collaboration.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="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;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" id="z521bb4d87bde44438315d0357594684e" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;"&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; font-weight: bold;"&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" id="z4f09e68bc310414da3f8c21b01c69cf7" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; 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" id="z07de37c6b51c4fc88763fe24db3b198d" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; 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" id="z5396a4f6f6264d808bb0b0970fbbf949" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; 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" id="z221f267a899d491f913d8e1746b6362a" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; 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" id="zca7ebdde125e410485d2be933fa84a5b" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; font-style: italic;"&gt;2&lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; font-style: italic;"&gt;.&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; font-weight: bold;"&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. We typically have only one performance obligation at the inception of a contract, which is to perform R&amp;amp;D 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;"&gt;Often we enter into a collaboration agreement in which we provide our partner with an option to license a medicine in the future. We may also provide our partner with an option to request that we provide additional goods or services in the future, such as active pharmaceutical ingredient, or API. We evaluate whether these options are material rights at the inception of the agreement. If we determine an option is a material right, we will consider the option a separate performance obligation. Historically, we have concluded that the options we grant to license a medicine in the future or to provide additional goods and services as requested by our partner are not material rights because these items are contingent upon future events that may not occur and are not priced at a significant discount. When a partner exercises its option to license a medicine or requests additional goods or services, then we identify a new performance obligation for that item&lt;/span&gt;.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In some cases, we deliver a license at the start of an agreement. If we determine that our partner has full use of the license and we do not have any additional material performance obligations related to the license after delivery, then we consider the license to be a separate performance obligation.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z89d2a19ad3fd4d87aa3b3cc055a6b623" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;"&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; font-weight: bold;"&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;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Milestone payments are our most common type of variable consideration. We recognize milestone payments using the most likely amount method because we will either receive the milestone payment or we will not, which makes the potential milestone payment a binary event. The most likely amount method requires us to determine the likelihood of earning the milestone payment. We include a milestone payment in the transaction price once it is probable we will achieve the milestone event. Most often, we do not consider our milestone payments probable until we or our partner achieve the milestone event because the majority of our milestone payments are contingent upon events that are not within our control and/ or are usually based on scientific progress which is inherently uncertain. For example, in the &lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;fourth&lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; quarter of &lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;2020&lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;, we earned&lt;/span&gt; a $20 million &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;milestone payment from AstraZeneca when AstraZeneca initiated a Phase &lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;2&lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;b study for ION&lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;449&lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;, our medicine in development targeting PCSK&lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;9&lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; to lower LDL-cholesterol. We did not consider the milestone payment probable until AstraZeneca achieved the milestone event because advancing ION&lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;449&lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; was contingent on AstraZeneca initiating a Phase &lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;2&lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;b study and was not within our control. We recognized the milestone payment in full in the period the milestone event was achieved because we did not have any remaining performance obligations related to the milestone payment&lt;/span&gt;.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z33954e5741c04959a455f20a29c4e558" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;"&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; font-style: italic; font-weight: bold;"&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" id="ze5360aeaac0b4e27ae12ac8253b06398" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; 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" id="z10d63e5de2314c06ad22cc7840776d39" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; 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" id="zba714425a66248a085047d1335e5f538" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; 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" id="zbd24a106c9494a478e217043fc30b768" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; 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;Expenses we expect to incur;&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z77f6cf0e489e4770a51c02ff69b03c42" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; 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" id="z55a0f09a57a440e78616543b799da651" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; 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" id="zb8283a4050434163907eb1ceed915b35" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; 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 number of internal hours we estimate 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" id="z1836887ec24a41eab911e7b298d0794f" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; 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" id="z00a44e034e0c47d3bd2e75356a388f81" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; 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" id="z3ae90bb9080943f2b46aad96c46d875e" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; 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" id="ze208c18727bc49289f50b3daf6d37408" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;"&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; font-weight: bold;"&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;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&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;/span&gt; Refer to Note 6, &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 the cumulative catch up adjustment we made.&lt;/div&gt;

&lt;div&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;The following are examples of when we typically recognize revenue based on the types of payments we receive.&lt;/div&gt;

&lt;div&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="text-decoration: underline;"&gt;Commercial Revenue: SPINRAZA royalties and Licensing and other royalty revenue&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We recognize royalty revenue, including royalties from SPINRAZA sales, in the period in which the counterparty sells the related product and recognizes the related revenue, which in certain cases may require us to estimate our royalty revenue&lt;/span&gt;.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;&lt;span style="text-decoration: underline;"&gt;Commercial Revenue: Product sales, net&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 recognize product sales in the period when our customer obtains control of our products, which occurs at a point in time upon transfer of title to the customer. We classify payments to customers or other parties in the distribution channel for services that are distinct and priced at fair value as selling, general and administrative, or SG&amp;amp;A, expenses in our consolidated statements of operations. Otherwise, payments to customers or other parties in the distribution channel that do not meet those criteria are classified as a reduction of revenue, as discussed further below. We exclude from revenues taxes collected from customers relating to product sales and remitted to governmental authorities&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;Reserves for Product 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;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We record product sales at our net sales price, or transaction price. We include in our transaction price estimated reserves for discounts, returns, chargebacks, rebates and other allowances that we offer within contracts between us and our customers, wholesalers, health care providers and other indirect customers. We estimate our reserves using the amounts we have earned or what we can claim on the associated sales. We classify our reserves as a reduction of accounts receivable when we are not required to make a payment or as a current liability when we are required to make a payment. In certain cases, our estimates include a range of possible outcomes that are probability weighted for relevant factors such as our historical experience, current contractual and statutory requirements, specific known market events and trends, industry data and forecasted customer buying and payment patterns. Overall, our reserves reflect our best estimates under the terms of our respective contracts. When calculating our reserves and related product sales, we only recognize amounts to the extent that we consider it probable that we would not have to reverse in a future period a significant amount of the cumulative sales we previously recognized. The actual amounts we receive may ultimately differ from our reserve estimates. If actual amounts in the future vary from our estimates, we will adjust these estimates, which would affect our net product sales in the respective period&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;"&gt;The following are the components of variable consideration related to product sales:&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="text-align: justify; margin-left: 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;Chargebacks: &lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;In the U.S., we estimate obligations resulting from contractual commitments with the government and other entities to sell products to qualified healthcare providers at prices lower than the list prices charged to our U.S. customer. Our U.S. customer charges us for the difference between what it pays for the product and the selling price to the qualified healthcare providers. We also estimate the amount of chargebacks related to our estimated product remaining in the distribution channel at the end of the reporting period that we expect our customer to sell to healthcare providers in future periods. We record these reserves as a reduction to contracts receivable on our consolidated balance sheet&lt;/span&gt;.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="text-align: justify; margin-left: 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;Government rebates&lt;/span&gt;&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;"&gt;We are subject to discount obligations under government programs, including Medicaid and Medicare programs in the U.S. and we record reserves for government rebates based on statutory discount rates and estimated utilization. We estimate Medicaid and Medicare rebates based on a range of possible outcomes that are probability weighted for the estimated payer mix. We record these reserves as an accrued liability on our consolidated balance sheet with a corresponding offset reducing our product sales in the same period we recognize the related sale. For Medicare, we also estimate the number of patients in the prescription drug coverage gap for whom we will owe an additional liability under the Medicare Part D program. On a quarterly basis, we update our estimates and record any adjustments in the period that we identify the adjustments&lt;/span&gt;.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="text-align: justify; margin-left: 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;Managed care rebates: &lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We are subject to rebates in connection with agreements with certain contracted commercial payers. We record these rebates as a liability on our consolidated balance sheet in the same period we recognize the related revenue. We estimate our managed care rebates based on our estimated payer mix and the applicable contractual rebate rate&lt;/span&gt;.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="text-align: justify; margin-left: 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;Trade discounts: &lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We provide customary invoice discounts on product sales to our U.S. customer for prompt payment. We record this discount as a reduction of product sales in the period in which we recognize the related product revenue&lt;/span&gt;.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="text-align: justify; margin-left: 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;Distribution services&lt;/span&gt;: &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We receive and pay for various distribution services from our U.S. and European customers (prior to our agreement with Sobi) and wholesalers in the U.S. We classify the costs for services we receive that are either not distinct from the sale of the product or for which we cannot reasonably estimate the fair value as a reduction of product sales. To the extent that the services we receive are distinct from the sale of the product, we classify the costs for such services as SG&amp;amp;A expenses.&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="text-align: justify; margin-left: 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;Product returns: &lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Our U.S. customer has return rights and the wholesalers have limited return rights primarily related to the product&#x2019;s expiration date. We estimate the amount of product sales that our customer may return. We record our return estimate as an accrued refund liability on our consolidated balance sheet with a corresponding offset reducing our product sales in the same period we recognize the related sale. Based on our distribution model for product sales, contractual inventory limits with our customer and wholesalers and the price of the product, we have had minimal returns to date and we believe we will continue to have minimal returns in the U.S. Our European customers generally only take title to the product after they receive an order and therefore they do not maintain excess inventory levels of our products. Accordingly, we have limited return risk in Europe and we do not estimate returns in Europe&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;&lt;span style="text-decoration: underline;"&gt;Research and development revenue under collaboration 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: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;&lt;span style="text-decoration: underline;"&gt;Upfront payments&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;When we enter into a collaboration agreement with 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. For example, under our collaboration agreement with Roche to&lt;/span&gt;&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;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; for the treatment of complement-mediated diseases, we received a $&lt;/span&gt;75&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million upfront payment in the fourth quarter of 2018. We allocated the upfront payment to our single performance obligation, R&amp;amp;D services. We are amortizing the $&lt;/span&gt;75&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million upfront payment using an input method over the estimated period of time we are providing 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; font-style: italic;"&gt;&lt;span style="text-decoration: underline;"&gt;Milestone payments&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 are required to include additional consideration in the transaction price when it is probable. We typically include milestone payments for R&amp;amp;D services in the transaction price when they are achieved. We include these milestone payments when they are achieved because typically there is considerable uncertainty in the research and development processes that trigger these payments. Similarly, we include approval milestone payments in the transaction price once the medicine is approved by the applicable regulatory agency. We will recognize sales-based milestone payments in the period in which we achieve the milestone under the sales-based royalty exception allowed under accounting rules.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&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 milestone payments that relate to an ongoing performance obligation over our period of performance. For example, in the &lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;fourth&lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; quarter of &lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;2020&lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;, we achieved a&lt;/span&gt; $7.5&#160;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;million milestone payment from Biogen when we advanced&lt;/span&gt;&#160;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;a &lt;/span&gt;target under our 2018 strategic collaboration.&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; We added this payment to the transaction price and allocated it to our R&amp;amp;D services performance obligation. We are recognizing revenue related to this milestone payment over our estimated period of performance&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;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. For example, in the third quarter of 2020, we recognized $18 million in milestone payments when Biogen initiated a Phase 1/2 trial for &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;ION464, our medicine in development targeting alpha-synuclein to treat patients with multiple system atrophy&lt;/span&gt;. &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We concluded that the milestone payments were not related to our R&amp;amp;D services performance obligation. Therefore, we recognized the milestone payments in full in the third quarter of 2020.&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;&lt;span style="text-decoration: underline;"&gt;License fees&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 generally recognize as revenue the total amount we determine to be the relative stand-alone selling price of a license when we deliver the license to our partner. This is because our partner has full use of the license and we do not have any additional performance obligations related to the license after delivery. For example, in the &lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;fourth&lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; quarter of &lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;2020&lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;, we earned a&lt;/span&gt; $30&#160;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;million license fee from AstraZeneca when AstraZeneca licensed ION&lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;455&lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;, an investigational medicine in development to treat nonalcoholic steatohepatitis, or NASH.&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;&lt;span style="text-decoration: underline;"&gt;Sublicense fees&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 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;For example, in the fourth quarter of 2020, we earned a $41.2 million sublicense fee from Alnylam Pharmaceuticals for its sublicense of our technology to Sanofi Genzyme.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;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;Amendments to 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;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" id="zc5f99d759c1848d881070e04e6c73535" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; 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" id="z64fa57d8d257481ab6fc670c67d5e2dc" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; 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 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 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;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;For example, in May 2015, we entered into an exclusive license agreement with Bayer to develop and commercialize IONIS-FXI&lt;/span&gt;&lt;sub&gt;Rx&lt;/sub&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; for the prevention of thrombosis. As part of the agreement, Bayer paid us a $&lt;/span&gt;100&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million upfront payment. At the onset of the agreement, we were responsible for completing a Phase 2 study of IONIS-FXI&lt;/span&gt;&lt;sub&gt;Rx&lt;/sub&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; in people with end-stage renal disease on hemodialysis and for providing an initial supply of API. In February 2017, we amended our agreement with Bayer to advance IONIS-FXI&lt;/span&gt;&lt;sub&gt;Rx&lt;/sub&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; and to initiate development of IONIS-FXI-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;, which Bayer licensed. As part of the 2017 amendment, Bayer paid us $&lt;/span&gt;75&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million. We are also eligible to receive milestone payments and tiered royalties on gross margins of IONIS-FXI&lt;/span&gt;&lt;sub&gt;Rx&lt;/sub&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; and IONIS-FXI-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;. Under the 2017 amendment, we concluded we had a new agreement with &lt;/span&gt;three&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; performance obligations. These performance obligations were to deliver the license of IONIS-FXI-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;, to provide R&amp;amp;D services and to deliver API. We allocated the $&lt;/span&gt;75&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million transaction price to these performance obligations. Refer to Note 6, &lt;/span&gt;&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;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;, &lt;/span&gt;in our audited financial statements included in our Annual Report on Form 10-K for the year ended December 31, 2019 &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;for further discussion of the Bayer 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;Multiple 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;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" id="z4eb4c38c616c425ca052b7ee9921b301" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; 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" id="z791c1b1e598245bfadb2be27fb53a91f" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; 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" id="zca4b2c0359fd49008d64fab4cf31367c" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; 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;For example, in the second quarter of 2018, we entered into two separate agreements with Biogen at the same time: &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;a new strategic neurology collaboration agreement and a stock purchase agreement, or SPA. We evaluated the Biogen agreements to determine whether we should treat the agreements separately or combine them. We considered that the agreements were negotiated concurrently and in contemplation of &lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;one&lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; another. Based on these facts and circumstances, we concluded that we should evaluate the provisions of the agreements on a combined basis&lt;/span&gt;&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: 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: -54pt; margin-left: 54pt; 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 on our consolidated balance sheet.&lt;/div&gt;

&lt;div&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 on our consolidated balance sheet.&lt;/span&gt; During the years ended December 31, 2020 and 2019, we recognized $100.4 million and $159.5 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 Products 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;Our cost of products sold includes 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 products sold. Prior to obtaining regulatory approval of TEGSEDI in July 2018 and WAYLIVRA in May 2019, we expensed as research and development expenses a significant portion of the costs we incurred to produce the initial commercial launch supply for each medicine.&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;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 and development expenses include wages, benefits, facilities, supplies, external services, clinical trial and manufacturing costs and other expenses that are directly related to our research and development operations. We expense research and development costs as we incur them. When we make payments for research and development services prior to the services being rendered, we record those amounts as prepaid assets on our consolidated balance sheet and we expense them as the services are provided. For the years ended December 31, 2020, 2019 and 2018, research and development expenses were $531.0 million, $461.5 million and $411.9 million, respectively. A portion of the costs included in research and development expenses are costs associated with our partner agreements. For the years ended December 31, 2020, 2019 and 2018, research and development costs of approximately $49.8 million, $83.2 million and $58.7 million, respectively, were related to our partner 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 capitalize costs consisting principally of outside legal costs and filing fees related to obtaining patents. We amortize patent costs over the useful life of the patent, beginning with the date the U.S. Patent and Trademark Office, or foreign equivalent, issues the patent. The weighted average remaining amortizable life of our issued patents was 10.3 years at December 31, 2020.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&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 cost of our patents capitalized on our consolidated balance sheet at December 31, 2020 and 2019 was $37.0 million and $34.0 million, respectively. Accumulated amortization related to patents was $9.1 million and $8.3 million at December 31, 2020 and 2019, 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;Based on our existing patents, we estimate amortization expense related to patents in each of the next five years to be the following:&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" id="z1566f0aad503425294fc597dc5e10f73" 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: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Year Ending 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;Amortization&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;(in millions)&lt;/div&gt;&lt;/td&gt;
    &lt;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;2021&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2.1&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 88%;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2022&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;2.0&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; 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;2023&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1.9&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 88%;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2024&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;1.7&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: 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;2025&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1.6&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/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 review our capitalized patent costs regularly to ensure that they include costs for patents and patent applications that have future value. When we identify patents and patent applications that we are not actively pursuing, we write off any associated costs. In 2020, 2019 and 2018, patent expenses were $4.1 million, $4.2 million and $2.6 million, respectively, and included non-cash charges related to the write-down of our patent costs to their estimated net realizable values of $1.9 million, $2.2 million and $0.8 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;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" id="zc442150657ce4320af53f69853dbac04" 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;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/&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;2020&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2019&lt;/div&gt;&lt;/td&gt;
    &lt;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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;39,477&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;24,461&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #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;8,264&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;10,289&lt;/div&gt;&lt;/td&gt;
    &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;11,559&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;6,020&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #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;30,861&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;25,999&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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;90,161&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;66,769&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Noncontrolling Interest in Akcea Therapeutics, Inc.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Since Akcea&#x2019;s IPO in July 2017 and prior to the Akcea Acquisition in October 2020, the shares of Akcea&#x2019;s common stock third parties owned represented an interest in Akcea&#x2019;s equity that we did not control. During this period our ownership ranged from &lt;/span&gt;68 percent&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; to &lt;/span&gt;77 percent&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;. However, as we maintained overall control of Akcea through our voting interest, we reflected the assets, liabilities and results of operations of Akcea in our consolidated financial statements. Since Akcea&#x2019;s IPO in July 2017 and through the closing of the Akcea Acquisition, we reflected the noncontrolling interest attributable to other owners of Akcea&#x2019;s common stock on a separate line on our statement of operations and a separate line within stockholders&#x2019; equity in our consolidated balance sheet. In addition, through the closing of the Akcea Acquisition, we recorded a noncontrolling interest adjustment to account for the stock options Akcea granted, which if exercised, would have diluted our ownership in Akcea. This adjustment was a reclassification within stockholders&#x2019; equity from additional paid-in capital to noncontrolling interest in Akcea equal to the amount of stock-based compensation expense Akcea had recognized. Additionally, w&lt;/span&gt;e reflected changes in our ownership percentage in our financial statements as an adjustment to noncontrolling interest in the period the change occurred.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;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;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 statement of operations. We use the specific identification method to determine the cost of securities sold.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We also have equity investments of less than 20 percent ownership in publicly and privately held biotechnology companies that we received as part of a technology license or partner agreement. At December 31, 2020, we held equity investments in two publicly held companies, ProQR Therapeutics N.V., or ProQR, and Antisense Therapeutics Limited, or ATL. We also held equity investments in seven privately-held companies, Aro Biotherapeutics, Atlantic Pharmaceuticals Limited, Dynacure SAS, Empirico, Inc., Flamingo Therapeutics BV, Seventh Sense Biosystems and Suzhou-Ribo Life Science Co, Ltd.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&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 statement of operations. We account for our equity investments in privately held companies at their cost minus impairments, plus or minus changes resulting from observable price changes in orderly transactions for the identical or similar investment of the same issuer. For example, &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;during the second and fourth quarters of 2020, we revalued our investments in &lt;/span&gt;three&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; privately held companies, Dynacure, Suzhou-Ribo and Aro Biotherapeutics because the companies sold additional equity securities that were similar to the equity we own. These observable price changes resulted in us recognizing a $&lt;/span&gt;6.3&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million gain on our investment in Dynacure, a $&lt;/span&gt;3.0&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million gain on our investment in Suzhou-Ribo and a $&lt;/span&gt;5.5&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million gain on our investment in Aro Biotherapeutics in our consolidated statement of operations during 2020 because the sales were at higher prices compared to our recorded value.&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;Inventory Valuation&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&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 on our consolidated balance sheet 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.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&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 obtained the first regulatory approval for TEGSEDI in July 2018 and for WAYLIVRA in May 2019. At December 31, 2020, our physical inventory for TEGSEDI and WAYLIVRA included API that we produced prior to when we obtained regulatory approval. As such, this API has no cost basis as we had previously expensed the costs as R&amp;amp;D expenses.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We 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. We recorded an &lt;span style="-sec-ix-hidden:Fact_b86d72920caa47448f2abd7be8e5c180"&gt;&lt;span style="-sec-ix-hidden:Fact_1261d93c836d4d94bba4bd8c45f1e569"&gt;insignificant&lt;/span&gt;&lt;/span&gt; amount of inventory write-offs during the years ended December 31, 2020 and 2019. We did not record any inventory write-offs for the year ended December 31, 2018.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;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" id="z420cf186c4154a629acd33b8e4e537ba" 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;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/&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;2020&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2019&lt;/div&gt;&lt;/td&gt;
    &lt;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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;9,206&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;9,363&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #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;7,502&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;6,520&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;16,708&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;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;15,883&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 76%;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Work in process&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2,252&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: 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;2,039&lt;/div&gt;&lt;/td&gt;
    &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;3,005&lt;/div&gt;&lt;/td&gt;
    &lt;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;258&lt;/div&gt;&lt;/td&gt;
    &lt;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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;21,965&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;18,180&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;div style="text-align: left;"&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Property, Plant and Equipment&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We carry our property, plant and equipment at cost and depreciate it on the straight-line method over its estimated useful life, which consists of the following (in thousands):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" id="z0d198c5954a847b59f5bfeab5aaeb505" 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;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/&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;Estimated Useful Lives&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;December 31,&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;(in years)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2020&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2019&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Computer software, laboratory, manufacturing and other equipment&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;3 to 10&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;68,990&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;60,965&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;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Building, building improvements and building systems&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;15 to 40&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;137,879&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;119,830&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Land improvements&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;20&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;8,391&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2,853&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Leasehold improvements&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;5 to 15&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;17,263&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;13,600&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Furniture and fixtures&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;5 to 10&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;12,871&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;7,354&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 64%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;245,394&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: 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;204,602&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Less accumulated depreciation&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(87,379&lt;/div&gt;&lt;/td&gt;
    &lt;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;(74,013&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 64%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;158,015&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#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;130,589&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Land&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;23,062&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;23,062&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 64%; padding-bottom: 4px;" valign="bottom"&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#160;Total&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;181,077&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;153,651&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We depreciate our leasehold improvements using the shorter of the estimated useful life or remaining lease term.&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;Fair Value of Financial Instruments&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; &lt;/span&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We have estimated the fair value of our financial instruments. The amounts reported for cash, accounts receivable, accounts payable and accrued expenses approximate the fair value because of their short maturities. We report our investment securities at their estimated fair value based on quoted market prices for identical or similar instruments.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="text-align: 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 on our consolidated balance sheet 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 concluded we were reasonably certain that we will 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 current leases do not provide an interest rate implicit in the lease, we used our incremental borrowing rate, based on the information available on the date we adopted Topic 842 (January 2019), 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. 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;Long-Lived Assets&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; &lt;/span&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We evaluate long-lived assets, which include property, plant and equipment and patent costs, 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. We recorded charges of $1.9 million, $2.2 million and $0.8 million for the years ended December 31, 2020, 2019 and 2018, respectively, related to the write-down of patents.&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;The preparation of consolidated financial statements in conformity with accounting principles generally accepted in the U.S. requires management to make estimates and assumptions that affect the amounts reported in the consolidated financial statements and accompanying notes. Actual results could differ from those 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;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, 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 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. We estimate the expected term of options granted based on 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;We recognize compensation expense for option awards and RSUs 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;"&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 vest annually over a four-year period. RSUs granted after June 2020 to our board of directors vest annually.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;See Note 4, &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;Accumulated Other Comprehensive Loss&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Accumulated other comprehensive loss is comprised of unrealized gains and losses on investments, net of taxes and currency translation adjustments. The following table summarizes changes in accumulated other comprehensive loss for the years ended December 31, &lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;2020&lt;/span&gt;&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;"&gt;2019&lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; and &lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;2018&lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; (in thousands):&lt;/span&gt;&lt;/div&gt;

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

&lt;table cellpadding="0" cellspacing="0" id="z0f84e575a1a8436991d62963b2899dd6" 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;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/&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;2020&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2019&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; 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;2018&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Beginning balance accumulated other comprehensive loss&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(25,290&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(32,016&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times 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;(31,759&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 64%;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Unrealized gains (losses) on securities, net of tax (1)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;3,729&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;6,633&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: 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;(280&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&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: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Currency translation adjustment&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;617&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;93&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-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;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 64%; padding-bottom: 2px;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Adjustments to other comprehensive loss from purchase of noncontrolling interest of Akcea Therapeutics, Inc.&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(127&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;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: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Net other comprehensive loss for the period&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;4,219&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #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;6,726&lt;/div&gt;&lt;/td&gt;
    &lt;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;(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;&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: 4px;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Ending balance accumulated other comprehensive loss&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(21,071&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(25,290&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(32,016&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;________________&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z9ecfa3f5cf504526a0786f25593849bf" 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; align: right;"&gt;&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(1)&lt;/div&gt;&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top;"&gt;&lt;div style="text-align: justify; text-indent: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We did not have tax expense included in our other comprehensive loss for the year ended December 31, 2020. For the years ended December 31, 2019 and 2018, we had a tax benefit $1.4 million and $0.3 million included in other comprehensive loss respectively.&#160;&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&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;At issuance, we accounted for our convertible debt instruments, including our 0.125 percent senior convertible notes, or 0.125% Notes, and 1 percent senior convertible notes, or 1% Notes, that may be settled in cash upon conversion (including partial cash settlement) by separating the liability and equity components of the instruments in a manner that reflects our nonconvertible debt borrowing rate on the date the notes were issued. In reviewing debt issuances, we were not able to identify any comparable companies that issued non-convertible debt instruments at the time of the issuance of the convertible notes. Therefore, we estimated the fair value of the liability component of our notes by using assumptions that market participants would use in pricing a debt instrument, including market interest rates, credit standing, yield curves and volatilities.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&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 assigned a value to the debt component of our convertible notes equal to the estimated fair value of similar debt instruments without the conversion feature, which resulted in us recording our debt at a discount. We are amortizing our debt issuance costs and debt discount over the life of the convertible notes as additional non-cash interest expense utilizing the effective interest method. For additional information, see Note 3, &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;.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&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% Notes mature in November 2021. Therefore, as of December 31, 2020, we classified the liability component of the 1% Notes as a current liability on our consolidated balance sheet.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&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 2020, the FASB issued guidance simplifying the accounting for convertible debt instruments. See the section titled &#x201c;Impact of Recently Issued Accounting Standards&#x201d; below for details.&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;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 0.125% Notes, we entered into a call spread transaction, which was 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 Derivatives and Hedging &#x2013; Contracts in Entity&#x2019;s Own Equity 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 sheet. We reassess our ability to continue to classify the note hedges and warrants in shareholders&#x2019; equity at each reporting period.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;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;Through 2020, we had two operating segments, our Ionis Core segment and Akcea Therapeutics. &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Akcea was focused on developing and commercializing medicines to treat patients with serious and rare diseases. We have provided segment financial information and results for our Ionis Core segment and our Akcea Therapeutics segment based on the segregation of revenues and expenses that our chief decision maker reviewed to assess operating performance and to make operating decisions through 2020. We allocated a portion of Ionis&#x2019; development, R&amp;amp;D support and general and administrative expenses to Akcea for work Ionis performed on behalf of Akcea and we billed Akcea for these expenses.&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;Fair Value Measurements&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We use a three-tier fair value hierarchy to prioritize the inputs used in our fair value measurements. These tiers include: Level 1, defined as observable inputs such as quoted prices in active markets for identical assets, which includes our money market funds and treasury securities classified as available-for-sale securities and our investment in equity securities in publicly held biotechnology companies; Level 2, defined as inputs other than quoted prices in active markets that are either directly or indirectly observable, which includes our fixed income securities and commercial paper classified as available-for-sale securities; and Level 3, defined as unobservable inputs in which little or no market data exists, therefore requiring us to develop our own assumptions. We classify most of our securities as Level 2. We obtain the fair value of our Level 2 investments from our custodian bank or from a professional pricing service. We validate the fair value of our Level 2 investments by understanding the pricing model used by the custodian banks or professional pricing service provider and comparing that fair value to the fair value based on observable market prices.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The following tables present the major security types we held at December 31, 2020 and 2019&#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;. At December 31, 2019, our ProQR investment was &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;subject to trading restrictions until the fourth quarter of 2020, as a result we&lt;/span&gt; included a lack of marketability discount in valuing this investment, which is a Level 3 input. As of December 31, 2020, our ProQR investment was no longer subject to trading restrictions. As of December 31, 2020, we did not have any investments which we valued using Level 3 inputs. The following tables segregate each security type by the level within the fair value hierarchy of the valuation techniques we utilized to determine the respective securities&#x2019; fair value (in thousands):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" id="z6070756b157447b980511cdf4857d355" 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;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 8pt;"/&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;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, 2020&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Quoted Prices in&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Active Markets&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;(Level 1)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Significant Other&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Observable Inputs&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;(Level 2)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Cash equivalents (1)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;221,125&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;221,125&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-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;846,315&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: 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;846,315&lt;/div&gt;&lt;/td&gt;
    &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 (4)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;174,861&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;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;174,861&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;/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;358,497&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: 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;358,497&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: 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 (4)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;136,309&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-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;136,309&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #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 (4)&lt;/div&gt;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;6,225&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;6,225&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#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;Investment in ProQR Therapeutics N.V. (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;2,031&lt;/div&gt;&lt;/td&gt;
    &lt;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;2,031&lt;/div&gt;&lt;/td&gt;
    &lt;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;1,745,363&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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;581,653&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;1,163,710&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" id="z42641d00b2bd400e81caba6eddf342f0" 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="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;At&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;December 31, 2019&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; 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;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;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Significant Other&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Observable Inputs&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;(Level 2)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Significant&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Unobservable Inputs&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;(Level 3)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Cash equivalents (1)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;418,406&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;418,406&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Corporate debt securities (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;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,102,568&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: 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;1,102,568&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by U.S. government agencies (7)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;329,404&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-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;329,404&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by the U.S. Treasury (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;363,694&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: 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;363,694&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by states of the U.S. and political subdivisions of the states (4)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;40,407&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-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;40,407&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; 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;Investment in ProQR Therapeutics N.V. (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;4,506&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;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;4,506&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: 52%; 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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2,258,985&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;782,100&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,472,379&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;4,506&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" id="z791574a09f2444c599172d57b45fe997" 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; vertical-align: top; align: right; 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 on our consolidated balance sheet.&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" id="za3c5f136d4254206a5ec01a41ea4efb9" 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; vertical-align: top; align: right; 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;$10.0 million included in cash and cash equivalents on our consolidated balance sheet, with the difference included in short-term investments on our consolidated balance sheet.&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" id="z148638abbe4544afb1bfb13a3a3df99e" 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; vertical-align: top; align: right; 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;$17.5 million included in cash and cash equivalents on our consolidated balance sheet, with the difference included in short-term investments on our consolidated balance sheet.&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" id="zfe5f26749b614dbcb042f4c2f2ba5a12" 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; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(4)&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Included in short-term investments.&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z7c2aa671a6d84170836be6a95eff7f0e" 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; vertical-align: top; align: right; 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 on our consolidated balance sheet.&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" id="zae152b0de27346b784a63d2fad55dc16" 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; vertical-align: top; align: right; 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;$19.0 million included in cash and cash equivalents on our consolidated balance sheet, with the difference included in short-term investments on our consolidated balance sheet.&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" id="z13ffd34009fd4d8ea5be9d956bd94c78" 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; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(7)&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;$0.8 million included in cash and cash equivalents on our consolidated balance sheet, with the difference included in short-term investments on our consolidated balance sheet.&#160; &lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&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, no assurance can be given that the final tax outcome of these matters will not be different from that which is 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 such determination is made.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&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.&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; 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;/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 do not provide for a U.S. income tax liability and foreign withholding taxes on undistributed foreign earnings of our foreign subsidiaries.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Impact of 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 June 2016, the FASB issued guidance that changes the measurement of credit losses for most financial assets and certain other instruments. If we have credit losses, this updated guidance requires us to record allowances for these instruments under a new expected credit loss model. This model requires us to estimate the expected credit loss of an instrument over its lifetime, which represents the portion of the amortized cost basis we do not expect to collect. The new guidance requires us to remeasure our allowance in each reporting period we have credit losses. We adopted this new guidance on January 1, 2020. This guidance did not have an impact on our consolidated financial statements.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In August 2018, the FASB issued clarifying guidance on how to account for implementation costs related to cloud-servicing arrangements. The guidance states that if these fees qualify to be capitalized and amortized over the service period, they need to be expensed in the same line item as the service expense and recognized in the same balance sheet category. The update can be applied either retrospectively or prospectively to all implementation costs incurred after the date of adoption. We adopted this guidance on January 1, 2020 on a prospective basis. This guidance did not have an impact on our consolidated financial statements.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In November 2018, the FASB issued clarifying guidance of the interaction between the collaboration accounting guidance and the new revenue recognition guidance we adopted on January 1, 2018 (Topic 606). Below is the clarifying guidance and how we implemented it (in italics):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="zf1701d3f1d8d4160978d38fc5e5b4c66" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; 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;When a participant is considered a customer in a collaborative arrangement, all of the associated accounting under Topic 606 should be applied.&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z3d884347466d4766902ab98141f40262" 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: 72pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&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; font-style: italic;"&gt;We are applying all of the associated accounting under Topic 606 when we determine a participant in a collaborative arrangement is a customer.&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="zbefb18546da74bf487f114918d77add3" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; 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;Adds &#x201c;unit of account&#x201d; concept to collaboration accounting guidance to align with Topic 606. The &#x201c;unit of account&#x201d; concept is used to determine if revenue is recognized or if a contra expense is recognized from consideration received under a collaboration.&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z28c82932c2e1414281433d5974927174" 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: 72pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&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; font-style: italic;"&gt;We use the &#x201c;unit of account&#x201d; concept when we receive consideration under a collaborative arrangement to determine when we recognize revenue or a contra expense.&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="za50af4149c204796bc74ae610430cd43" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; 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;The clarifying guidance precludes us from recognizing revenue under Topic 606 when we determine a transaction with a collaborative partner is not a customer and is not directly related to the sales to third parties.&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="zd9d21a16a5b3482c85eb10cf58a06d3e" 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: 72pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&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; font-style: italic;"&gt;When we conclude a collaboration partner is not a customer and is not directly related to the sales to third parties, we do not recognize revenue for the transaction.&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 adopted this new guidance on January 1, 2020. This guidance did not have any impact on our consolidated financial statements.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;In August 2020, the FASB issued guidance &lt;/span&gt;which simplifies the accounting for convertible instruments&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;, amends the guidance on derivative scope exceptions for contracts in an entity&#x2019;s own equity, and modifies the guidance on diluted earnings per share calculations as a result of these changes. Under our current outstanding convertible debt arrangements, we anticipate the following impacts:&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="zcbb885b9cab547a1b31cd283712248a2" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 36pt; vertical-align: top; align: right; 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;We will no longer separate our existing convertible debt into liability and equity components. Therefore, we will no longer recognize a debt discount for the value of the conversion option, instead we will record the face value of the convertible debt as a liability on our consolidated balance sheet;&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z66fb90d1a5be4351bc55d49e62d382d6" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; 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;We will record cash interest expense plus amortization of debt issuance costs to interest expense. Since we will not recognize a debt discount, we will no longer record the amortization of a debt discount to interest expense; and&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="ze1e1f5e6552b4bfc822ec7f94c42c685" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; 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;We do not expect our EPS calculation to not change under this update. We plan to continue to use the if-converted method to calculate diluted earnings per share.&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 plan to adopt this guidance in the first quarter of 2021 under the full retrospective approach, meaning we will apply the guidance to all periods presented beginning in the first quarter of 2021.&lt;/div&gt;
</us-gaap:OrganizationConsolidationBasisOfPresentationBusinessDescriptionAndAccountingPoliciesTextBlock>
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&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;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;In our consolidated financial statements we included the accounts of Ionis Pharmaceuticals, Inc. and the consolidated results of our subsidiary, Akcea Therapeutics, Inc. and its wholly owned subsidiaries (&#x201c;we&#x201d;, &#x201c;us&#x201d; or &#x201c;our&#x201d;). We formed Akcea in December 2014. In July 2017, Akcea completed an initial public offering, or IPO. Prior to Akcea&#x2019;s IPO in July 2017, we owned &lt;/span&gt;100 percent&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; of Akcea. In October 2020, we acquired the shares of Akcea&#x2019;s common stock we did not own. We will refer to this transaction as the Akcea Acquisition throughout the remainder of this document. &lt;/span&gt;See Note 7, &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Akcea Acquisition&lt;/span&gt;, in the Notes to the Consolidated Financial Statements for further details.&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; We reflected changes in our ownership percentage in our financial statements as an adjustment to noncontrolling interest in the period the change occurred.&lt;/span&gt;&lt;/div&gt;
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      contextRef="c20200101to20201231"
      id="Text_2323891966f5407ca4c6808ff9b85566">
&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Basic and Diluted Net Income (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 income (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 income (loss) per share by dividing the total net income (loss) attributable to our common stockholders 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;"&gt;The calculation of total net income (loss) attributable to our common stockholders for each year considered our net income (loss) for Ionis on a stand-alone basis plus our share of Akcea&#x2019;s net income (loss) for the period. To calculate the portion of Akcea&#x2019;s net income (loss) attributable to our ownership for each year, we multiplied Akcea&#x2019;s income (loss) per share by the weighted average shares we owned in Akcea during the period. As a result of this calculation, our total net income (loss) available to Ionis common stockholders for the calculation of net income (loss) per share is different than net income (loss) attributable to Ionis Pharmaceuticals, Inc. common stockholders in our consolidated statements of operations for each 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;"&gt;Our basic net income (loss) per share was calculated as follows (in thousands, except per share amounts):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" id="z52a07e9978cc42e1b09d31421865a2e3" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; border-bottom: #000000 2px solid; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Year Ended December 31, 2020&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Weighted&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Average Shares&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Owned in Akcea&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Akcea&lt;/span&gt;&#x2019;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;s&lt;/span&gt;&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Net Loss&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Per Share&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Basic Net Loss&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Per Share&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Calculation&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Akcea&#x2019;s net loss in the pre-acquisition period attributable to our ownership&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;77,095&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(1.45&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(111,775&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Akcea&#x2019;s net loss in the post-acquisition period attributable to our ownership&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(85,987&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Akcea&#x2019;s total net loss attributable to our ownership&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(197,762&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Ionis&#x2019; stand-alone net loss&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(253,725&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Net loss available to Ionis common stockholders&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(451,487&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Weighted average shares outstanding&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;139,612&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Basic net loss per share&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(3.23&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&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" id="z7190f4cfc9904c35afaf55ca55271bf2" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; border-bottom: #000000 2px solid; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Year Ended December 31, 2019&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Weighted&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Average Shares&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Owned in Akcea&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Akcea&lt;/span&gt;&#x2019;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;s&lt;/span&gt;&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Net Income&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Per Share&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Basic Net Income&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Per Share&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Calculation&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Common shares&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;70,100&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.49&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;34,073&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Akcea&#x2019;s net income attributable to our ownership&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;&#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%; 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;&#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%; 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;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&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;34,073&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Ionis&#x2019; stand-alone net income&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;262,490&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;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Net income available to Ionis common stockholders&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 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; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;296,563&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Weighted average shares outstanding&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;139,998&lt;/div&gt;&lt;/td&gt;
    &lt;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: top; width: 64%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Basic net income per share&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2.12&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" id="zc4df006abbbb4d5b9a0a303fb389d2b3" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; border-bottom: #000000 2px solid; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Year Ended December 31, 2018&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Weighted&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Average Shares&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Owned in Akcea&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Akcea&lt;/span&gt;&#x2019;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;s&lt;/span&gt;&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Net Loss&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Per Share&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Basic Net Income&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Per Share&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Calculation&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Common shares&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;59,812&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(2.74&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;(163,938&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Akcea&#x2019;s net loss attributable to our ownership&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;&#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%; 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;&#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%; 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;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&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;(163,938&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Ionis&#x2019; stand-alone net income&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;440,806&lt;/div&gt;&lt;/td&gt;
    &lt;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: top; width: 64%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Net income available to Ionis common stockholders&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 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; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;276,868&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Weighted average shares outstanding&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;132,320&lt;/div&gt;&lt;/td&gt;
    &lt;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: top; width: 64%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Basic net income per share&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2.09&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; font-style: italic;"&gt;Diluted net income 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 year ended December 31, 2020, we incurred a net loss; therefore, we did not include dilutive common equivalent shares in the computation of diluted net loss per share because the effect would have been anti-dilutive. Common stock 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" id="za661525f8bef42ea9eb273beec8c3ffa" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; 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;&lt;/span&gt;&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="zcb135ba690824483aa0fa909f89a6a2a" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1 percent&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; convertible senior notes;&lt;/span&gt;&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="zd9638f50b7c74568a481c388188fcd9b" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; 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" id="zbac81e814d3144cfb944e6b840054211" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; 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; and&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="za8f44a91052a49768a8cab1258c98733" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; 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;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;For the years ended December 31, 2019 and 2018, we had net income available to Ionis common stockholders. As a result, we computed diluted net income per share using the weighted-average number of common shares and dilutive common equivalent shares outstanding during each period.&lt;/span&gt; We calculated our diluted net income per share as follows &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;(in thousands except per share amounts):&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" id="zbebb8966d0bf411b9c7f046d05640cb2" 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;Year Ended December 31, 2019&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Income&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;(Numerator)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Shares&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;(Denominator)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Per-Share&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Amount&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Net income available to Ionis common stockholders&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;296,563&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;139,998&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;2.12&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Effect of dilutive securities:&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -8.9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Shares issuable upon exercise of stock options&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2,090&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: 0.1pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Shares issuable upon restricted stock award issuance&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;766&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Shares issuable related to our ESPP&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #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;18&lt;/div&gt;&lt;/td&gt;
    &lt;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%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 4px;" 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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;296,563&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;142,872&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;2.08&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" id="zd2aad674b25d40a39b5785fe82a18973" 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;Year Ended December 31, 2018&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Income&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;(Numerator)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Shares&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;(Denominator)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Per-Share&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Amount&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Net income available to Ionis common stockholders&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;276,868&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;132,320&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;2.09&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Effect of dilutive securities:&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -8.9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Shares issuable upon exercise of stock options&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,216&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: 0.1pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Shares issuable upon restricted stock award issuance&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;514&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Shares issuable related to our ESPP&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #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;6&lt;/div&gt;&lt;/td&gt;
    &lt;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%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 4px;" 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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;276,868&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;134,056&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;2.07&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 each year presented, the calculation excluded our convertible senior notes because the effect on diluted earnings per share was anti-dilutive.&lt;/div&gt;
</us-gaap:EarningsPerSharePolicyTextBlock>
    <us-gaap:ScheduleOfEarningsPerShareBasicByCommonClassTextBlock
      contextRef="c20200101to20201231"
      id="Text_6255ce3fc5024406b256c4e5a5be9dd3">
&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Our basic net income (loss) per share was calculated as follows (in thousands, except per share amounts):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" id="z52a07e9978cc42e1b09d31421865a2e3" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; border-bottom: #000000 2px solid; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Year Ended December 31, 2020&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Weighted&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Average Shares&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Owned in Akcea&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Akcea&lt;/span&gt;&#x2019;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;s&lt;/span&gt;&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Net Loss&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Per Share&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Basic Net Loss&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Per Share&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Calculation&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Akcea&#x2019;s net loss in the pre-acquisition period attributable to our ownership&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;77,095&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(1.45&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(111,775&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Akcea&#x2019;s net loss in the post-acquisition period attributable to our ownership&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(85,987&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Akcea&#x2019;s total net loss attributable to our ownership&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(197,762&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Ionis&#x2019; stand-alone net loss&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(253,725&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Net loss available to Ionis common stockholders&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(451,487&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Weighted average shares outstanding&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;139,612&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Basic net loss per share&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(3.23&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&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" id="z7190f4cfc9904c35afaf55ca55271bf2" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; border-bottom: #000000 2px solid; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Year Ended December 31, 2019&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Weighted&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Average Shares&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Owned in Akcea&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Akcea&lt;/span&gt;&#x2019;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;s&lt;/span&gt;&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Net Income&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Per Share&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Basic Net Income&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Per Share&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Calculation&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Common shares&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;70,100&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.49&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;34,073&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Akcea&#x2019;s net income attributable to our ownership&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;&#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%; 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;&#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%; 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;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&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;34,073&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Ionis&#x2019; stand-alone net income&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;262,490&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;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Net income available to Ionis common stockholders&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 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; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;296,563&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Weighted average shares outstanding&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;139,998&lt;/div&gt;&lt;/td&gt;
    &lt;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: top; width: 64%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Basic net income per share&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2.12&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" id="zc4df006abbbb4d5b9a0a303fb389d2b3" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; border-bottom: #000000 2px solid; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Year Ended December 31, 2018&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Weighted&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Average Shares&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Owned in Akcea&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Akcea&lt;/span&gt;&#x2019;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;s&lt;/span&gt;&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Net Loss&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Per Share&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Basic Net Income&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Per Share&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Calculation&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Common shares&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;59,812&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(2.74&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;(163,938&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Akcea&#x2019;s net loss attributable to our ownership&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;&#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%; 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;&#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%; 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;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&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;(163,938&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Ionis&#x2019; stand-alone net income&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;440,806&lt;/div&gt;&lt;/td&gt;
    &lt;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: top; width: 64%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Net income available to Ionis common stockholders&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 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; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;276,868&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Weighted average shares outstanding&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;132,320&lt;/div&gt;&lt;/td&gt;
    &lt;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;
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  &lt;tr&gt;
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    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2.09&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;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;For the years ended December 31, 2019 and 2018, we had net income available to Ionis common stockholders. As a result, we computed diluted net income per share using the weighted-average number of common shares and dilutive common equivalent shares outstanding during each period.&lt;/span&gt; We calculated our diluted net income per share as follows &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;(in thousands except per share amounts):&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" id="zbebb8966d0bf411b9c7f046d05640cb2" 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;Year Ended December 31, 2019&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Income&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;(Numerator)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Shares&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;(Denominator)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Per-Share&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Amount&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Net income available to Ionis common stockholders&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;296,563&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;139,998&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;2.12&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Effect of dilutive securities:&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -8.9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Shares issuable upon exercise of stock options&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2,090&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: 0.1pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Shares issuable upon restricted stock award issuance&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;766&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Shares issuable related to our ESPP&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #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;18&lt;/div&gt;&lt;/td&gt;
    &lt;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%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 4px;" 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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;296,563&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;142,872&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;2.08&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" id="zd2aad674b25d40a39b5785fe82a18973" 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;Year Ended December 31, 2018&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Income&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;(Numerator)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Shares&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;(Denominator)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Per-Share&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Amount&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Net income available to Ionis common stockholders&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;276,868&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;132,320&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;2.09&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Effect of dilutive securities:&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -8.9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Shares issuable upon exercise of stock options&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,216&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: 0.1pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Shares issuable upon restricted stock award issuance&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;514&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Shares issuable related to our ESPP&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #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;6&lt;/div&gt;&lt;/td&gt;
    &lt;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%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 4px;" 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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;276,868&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;134,056&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;2.07&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="text-align: justify; 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;&lt;span style="text-decoration: underline;"&gt;Our Revenue Sources&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 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 in deferred revenue on our consolidated balance sheet.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;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;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 will also recognize as commercial revenue sales milestone payments and royalties we earn under our other partnerships.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;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;Commercial Revenue: Product sales, 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 added product sales from TEGSEDI to our commercial revenue in the fourth quarter of 2018 and we added product sales from WAYLIVRA to our commercial revenue in the third quarter of 2019. &lt;/span&gt;In the U.S., we distribute TEGSEDI through an exclusive distribution agreement with a third-party logistics company, or 3PL, that takes title to TEGSEDI. The 3PL is our sole customer in the U.S. The 3PL then distributes TEGSEDI to a specialty pharmacy and a specialty distributor, which we collectively refer to as wholesalers, who then distribute TEGSEDI to health care providers and patients.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&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 Europe, through 2020 we sold TEGSEDI and WAYLIVRA to hospitals and pharmacies using 3PLs as distributors. Beginning in 2021, we are commercializing TEGSEDI and WAYLIVRA in Europe through a distribution agreement with Swedish Orphan Biovitrum AB, or Sobi, an international biopharmaceutical company that focuses on rare diseases. Under the terms of this agreement, we retained the marketing authorization for both medicines in Europe.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&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 Latin America beginning in 2020, we sold TEGSEDI and WAYLIVRA to our partner, PTC Therapeutics. Under our collaboration agreement with PTC, PTC is commercializing TEGSEDI and WAYLIVRA in Latin America and Caribbean countries.&lt;/div&gt;

&lt;div&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 collaborative 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 often 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, research and development, or R&amp;amp;D, services, and manufacturing services.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We provide details about our collaboration agreements in Note 6, &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;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;&#160;&lt;/span&gt;Under each collaboration note we discuss our specific revenue recognition conclusions, including our significant performance obligations under each collaboration.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="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;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" id="z521bb4d87bde44438315d0357594684e" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;"&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; font-weight: bold;"&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" id="z4f09e68bc310414da3f8c21b01c69cf7" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; 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" id="z07de37c6b51c4fc88763fe24db3b198d" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; 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" id="z5396a4f6f6264d808bb0b0970fbbf949" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; 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" id="z221f267a899d491f913d8e1746b6362a" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; 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" id="zca7ebdde125e410485d2be933fa84a5b" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; font-style: italic;"&gt;2&lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; font-style: italic;"&gt;.&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; font-weight: bold;"&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. We typically have only one performance obligation at the inception of a contract, which is to perform R&amp;amp;D 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;"&gt;Often we enter into a collaboration agreement in which we provide our partner with an option to license a medicine in the future. We may also provide our partner with an option to request that we provide additional goods or services in the future, such as active pharmaceutical ingredient, or API. We evaluate whether these options are material rights at the inception of the agreement. If we determine an option is a material right, we will consider the option a separate performance obligation. Historically, we have concluded that the options we grant to license a medicine in the future or to provide additional goods and services as requested by our partner are not material rights because these items are contingent upon future events that may not occur and are not priced at a significant discount. When a partner exercises its option to license a medicine or requests additional goods or services, then we identify a new performance obligation for that item&lt;/span&gt;.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In some cases, we deliver a license at the start of an agreement. If we determine that our partner has full use of the license and we do not have any additional material performance obligations related to the license after delivery, then we consider the license to be a separate performance obligation.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z89d2a19ad3fd4d87aa3b3cc055a6b623" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;"&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; font-weight: bold;"&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;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Milestone payments are our most common type of variable consideration. We recognize milestone payments using the most likely amount method because we will either receive the milestone payment or we will not, which makes the potential milestone payment a binary event. The most likely amount method requires us to determine the likelihood of earning the milestone payment. We include a milestone payment in the transaction price once it is probable we will achieve the milestone event. Most often, we do not consider our milestone payments probable until we or our partner achieve the milestone event because the majority of our milestone payments are contingent upon events that are not within our control and/ or are usually based on scientific progress which is inherently uncertain. For example, in the &lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;fourth&lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; quarter of &lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;2020&lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;, we earned&lt;/span&gt; a $20 million &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;milestone payment from AstraZeneca when AstraZeneca initiated a Phase &lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;2&lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;b study for ION&lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;449&lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;, our medicine in development targeting PCSK&lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;9&lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; to lower LDL-cholesterol. We did not consider the milestone payment probable until AstraZeneca achieved the milestone event because advancing ION&lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;449&lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; was contingent on AstraZeneca initiating a Phase &lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;2&lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;b study and was not within our control. We recognized the milestone payment in full in the period the milestone event was achieved because we did not have any remaining performance obligations related to the milestone payment&lt;/span&gt;.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z33954e5741c04959a455f20a29c4e558" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;"&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; font-style: italic; font-weight: bold;"&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" id="ze5360aeaac0b4e27ae12ac8253b06398" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; 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" id="z10d63e5de2314c06ad22cc7840776d39" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; 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" id="zba714425a66248a085047d1335e5f538" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; 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" id="zbd24a106c9494a478e217043fc30b768" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; 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;Expenses we expect to incur;&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z77f6cf0e489e4770a51c02ff69b03c42" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; 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" id="z55a0f09a57a440e78616543b799da651" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; 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" id="zb8283a4050434163907eb1ceed915b35" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; 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 number of internal hours we estimate 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" id="z1836887ec24a41eab911e7b298d0794f" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; 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" id="z00a44e034e0c47d3bd2e75356a388f81" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; 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" id="z3ae90bb9080943f2b46aad96c46d875e" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; 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" id="ze208c18727bc49289f50b3daf6d37408" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;"&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; font-weight: bold;"&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;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&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;/span&gt; Refer to Note 6, &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 the cumulative catch up adjustment we made.&lt;/div&gt;

&lt;div&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;The following are examples of when we typically recognize revenue based on the types of payments we receive.&lt;/div&gt;

&lt;div&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="text-decoration: underline;"&gt;Commercial Revenue: SPINRAZA royalties and Licensing and other royalty revenue&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We recognize royalty revenue, including royalties from SPINRAZA sales, in the period in which the counterparty sells the related product and recognizes the related revenue, which in certain cases may require us to estimate our royalty revenue&lt;/span&gt;.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;&lt;span style="text-decoration: underline;"&gt;Commercial Revenue: Product sales, net&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 recognize product sales in the period when our customer obtains control of our products, which occurs at a point in time upon transfer of title to the customer. We classify payments to customers or other parties in the distribution channel for services that are distinct and priced at fair value as selling, general and administrative, or SG&amp;amp;A, expenses in our consolidated statements of operations. Otherwise, payments to customers or other parties in the distribution channel that do not meet those criteria are classified as a reduction of revenue, as discussed further below. We exclude from revenues taxes collected from customers relating to product sales and remitted to governmental authorities&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;Reserves for Product 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;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We record product sales at our net sales price, or transaction price. We include in our transaction price estimated reserves for discounts, returns, chargebacks, rebates and other allowances that we offer within contracts between us and our customers, wholesalers, health care providers and other indirect customers. We estimate our reserves using the amounts we have earned or what we can claim on the associated sales. We classify our reserves as a reduction of accounts receivable when we are not required to make a payment or as a current liability when we are required to make a payment. In certain cases, our estimates include a range of possible outcomes that are probability weighted for relevant factors such as our historical experience, current contractual and statutory requirements, specific known market events and trends, industry data and forecasted customer buying and payment patterns. Overall, our reserves reflect our best estimates under the terms of our respective contracts. When calculating our reserves and related product sales, we only recognize amounts to the extent that we consider it probable that we would not have to reverse in a future period a significant amount of the cumulative sales we previously recognized. The actual amounts we receive may ultimately differ from our reserve estimates. If actual amounts in the future vary from our estimates, we will adjust these estimates, which would affect our net product sales in the respective period&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;"&gt;The following are the components of variable consideration related to product sales:&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="text-align: justify; margin-left: 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;Chargebacks: &lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;In the U.S., we estimate obligations resulting from contractual commitments with the government and other entities to sell products to qualified healthcare providers at prices lower than the list prices charged to our U.S. customer. Our U.S. customer charges us for the difference between what it pays for the product and the selling price to the qualified healthcare providers. We also estimate the amount of chargebacks related to our estimated product remaining in the distribution channel at the end of the reporting period that we expect our customer to sell to healthcare providers in future periods. We record these reserves as a reduction to contracts receivable on our consolidated balance sheet&lt;/span&gt;.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="text-align: justify; margin-left: 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;Government rebates&lt;/span&gt;&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;"&gt;We are subject to discount obligations under government programs, including Medicaid and Medicare programs in the U.S. and we record reserves for government rebates based on statutory discount rates and estimated utilization. We estimate Medicaid and Medicare rebates based on a range of possible outcomes that are probability weighted for the estimated payer mix. We record these reserves as an accrued liability on our consolidated balance sheet with a corresponding offset reducing our product sales in the same period we recognize the related sale. For Medicare, we also estimate the number of patients in the prescription drug coverage gap for whom we will owe an additional liability under the Medicare Part D program. On a quarterly basis, we update our estimates and record any adjustments in the period that we identify the adjustments&lt;/span&gt;.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="text-align: justify; margin-left: 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;Managed care rebates: &lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We are subject to rebates in connection with agreements with certain contracted commercial payers. We record these rebates as a liability on our consolidated balance sheet in the same period we recognize the related revenue. We estimate our managed care rebates based on our estimated payer mix and the applicable contractual rebate rate&lt;/span&gt;.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="text-align: justify; margin-left: 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;Trade discounts: &lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We provide customary invoice discounts on product sales to our U.S. customer for prompt payment. We record this discount as a reduction of product sales in the period in which we recognize the related product revenue&lt;/span&gt;.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="text-align: justify; margin-left: 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;Distribution services&lt;/span&gt;: &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We receive and pay for various distribution services from our U.S. and European customers (prior to our agreement with Sobi) and wholesalers in the U.S. We classify the costs for services we receive that are either not distinct from the sale of the product or for which we cannot reasonably estimate the fair value as a reduction of product sales. To the extent that the services we receive are distinct from the sale of the product, we classify the costs for such services as SG&amp;amp;A expenses.&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="text-align: justify; margin-left: 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;Product returns: &lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Our U.S. customer has return rights and the wholesalers have limited return rights primarily related to the product&#x2019;s expiration date. We estimate the amount of product sales that our customer may return. We record our return estimate as an accrued refund liability on our consolidated balance sheet with a corresponding offset reducing our product sales in the same period we recognize the related sale. Based on our distribution model for product sales, contractual inventory limits with our customer and wholesalers and the price of the product, we have had minimal returns to date and we believe we will continue to have minimal returns in the U.S. Our European customers generally only take title to the product after they receive an order and therefore they do not maintain excess inventory levels of our products. Accordingly, we have limited return risk in Europe and we do not estimate returns in Europe&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;&lt;span style="text-decoration: underline;"&gt;Research and development revenue under collaboration 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: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;&lt;span style="text-decoration: underline;"&gt;Upfront payments&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;When we enter into a collaboration agreement with 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. For example, under our collaboration agreement with Roche to&lt;/span&gt;&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;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; for the treatment of complement-mediated diseases, we received a $&lt;/span&gt;75&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million upfront payment in the fourth quarter of 2018. We allocated the upfront payment to our single performance obligation, R&amp;amp;D services. We are amortizing the $&lt;/span&gt;75&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million upfront payment using an input method over the estimated period of time we are providing 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; font-style: italic;"&gt;&lt;span style="text-decoration: underline;"&gt;Milestone payments&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 are required to include additional consideration in the transaction price when it is probable. We typically include milestone payments for R&amp;amp;D services in the transaction price when they are achieved. We include these milestone payments when they are achieved because typically there is considerable uncertainty in the research and development processes that trigger these payments. Similarly, we include approval milestone payments in the transaction price once the medicine is approved by the applicable regulatory agency. We will recognize sales-based milestone payments in the period in which we achieve the milestone under the sales-based royalty exception allowed under accounting rules.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&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 milestone payments that relate to an ongoing performance obligation over our period of performance. For example, in the &lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;fourth&lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; quarter of &lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;2020&lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;, we achieved a&lt;/span&gt; $7.5&#160;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;million milestone payment from Biogen when we advanced&lt;/span&gt;&#160;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;a &lt;/span&gt;target under our 2018 strategic collaboration.&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; We added this payment to the transaction price and allocated it to our R&amp;amp;D services performance obligation. We are recognizing revenue related to this milestone payment over our estimated period of performance&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;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. For example, in the third quarter of 2020, we recognized $18 million in milestone payments when Biogen initiated a Phase 1/2 trial for &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;ION464, our medicine in development targeting alpha-synuclein to treat patients with multiple system atrophy&lt;/span&gt;. &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We concluded that the milestone payments were not related to our R&amp;amp;D services performance obligation. Therefore, we recognized the milestone payments in full in the third quarter of 2020.&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;&lt;span style="text-decoration: underline;"&gt;License fees&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 generally recognize as revenue the total amount we determine to be the relative stand-alone selling price of a license when we deliver the license to our partner. This is because our partner has full use of the license and we do not have any additional performance obligations related to the license after delivery. For example, in the &lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;fourth&lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; quarter of &lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;2020&lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;, we earned a&lt;/span&gt; $30&#160;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;million license fee from AstraZeneca when AstraZeneca licensed ION&lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;455&lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;, an investigational medicine in development to treat nonalcoholic steatohepatitis, or NASH.&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;&lt;span style="text-decoration: underline;"&gt;Sublicense fees&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 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;For example, in the fourth quarter of 2020, we earned a $41.2 million sublicense fee from Alnylam Pharmaceuticals for its sublicense of our technology to Sanofi Genzyme.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;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;Amendments to 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;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" id="zc5f99d759c1848d881070e04e6c73535" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; 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" id="z64fa57d8d257481ab6fc670c67d5e2dc" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; 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 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 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;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;For example, in May 2015, we entered into an exclusive license agreement with Bayer to develop and commercialize IONIS-FXI&lt;/span&gt;&lt;sub&gt;Rx&lt;/sub&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; for the prevention of thrombosis. As part of the agreement, Bayer paid us a $&lt;/span&gt;100&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million upfront payment. At the onset of the agreement, we were responsible for completing a Phase 2 study of IONIS-FXI&lt;/span&gt;&lt;sub&gt;Rx&lt;/sub&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; in people with end-stage renal disease on hemodialysis and for providing an initial supply of API. In February 2017, we amended our agreement with Bayer to advance IONIS-FXI&lt;/span&gt;&lt;sub&gt;Rx&lt;/sub&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; and to initiate development of IONIS-FXI-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;, which Bayer licensed. As part of the 2017 amendment, Bayer paid us $&lt;/span&gt;75&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million. We are also eligible to receive milestone payments and tiered royalties on gross margins of IONIS-FXI&lt;/span&gt;&lt;sub&gt;Rx&lt;/sub&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; and IONIS-FXI-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;. Under the 2017 amendment, we concluded we had a new agreement with &lt;/span&gt;three&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; performance obligations. These performance obligations were to deliver the license of IONIS-FXI-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;, to provide R&amp;amp;D services and to deliver API. We allocated the $&lt;/span&gt;75&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million transaction price to these performance obligations. Refer to Note 6, &lt;/span&gt;&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;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;, &lt;/span&gt;in our audited financial statements included in our Annual Report on Form 10-K for the year ended December 31, 2019 &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;for further discussion of the Bayer 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;Multiple 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;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" id="z4eb4c38c616c425ca052b7ee9921b301" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; 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" id="z791c1b1e598245bfadb2be27fb53a91f" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; 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" id="zca4b2c0359fd49008d64fab4cf31367c" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; 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;For example, in the second quarter of 2018, we entered into two separate agreements with Biogen at the same time: &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;a new strategic neurology collaboration agreement and a stock purchase agreement, or SPA. We evaluated the Biogen agreements to determine whether we should treat the agreements separately or combine them. We considered that the agreements were negotiated concurrently and in contemplation of &lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;one&lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; another. Based on these facts and circumstances, we concluded that we should evaluate the provisions of the agreements on a combined basis&lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;.&lt;/span&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: 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;
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&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: -54pt; margin-left: 54pt; 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 on our consolidated balance sheet.&lt;/div&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: -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 on our consolidated balance sheet.&lt;/span&gt; During the years ended December 31, 2020 and 2019, we recognized $100.4 million and $159.5 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;
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&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Cost of Products 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;Our cost of products sold includes 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 products sold. Prior to obtaining regulatory approval of TEGSEDI in July 2018 and WAYLIVRA in May 2019, we expensed as research and development expenses a significant portion of the costs we incurred to produce the initial commercial launch supply for each medicine.&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;Our research and development expenses include wages, benefits, facilities, supplies, external services, clinical trial and manufacturing costs and other expenses that are directly related to our research and development operations. We expense research and development costs as we incur them. When we make payments for research and development services prior to the services being rendered, we record those amounts as prepaid assets on our consolidated balance sheet and we expense them as the services are provided. For the years ended December 31, 2020, 2019 and 2018, research and development expenses were $531.0 million, $461.5 million and $411.9 million, respectively. A portion of the costs included in research and development expenses are costs associated with our partner agreements. For the years ended December 31, 2020, 2019 and 2018, research and development costs of approximately $49.8 million, $83.2 million and $58.7 million, respectively, were related to our partner agreements.&lt;/div&gt;
</us-gaap:ResearchAndDevelopmentExpensePolicy>
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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;We capitalize costs consisting principally of outside legal costs and filing fees related to obtaining patents. We amortize patent costs over the useful life of the patent, beginning with the date the U.S. Patent and Trademark Office, or foreign equivalent, issues the patent. The weighted average remaining amortizable life of our issued patents was 10.3 years at December 31, 2020.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&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 cost of our patents capitalized on our consolidated balance sheet at December 31, 2020 and 2019 was $37.0 million and $34.0 million, respectively. Accumulated amortization related to patents was $9.1 million and $8.3 million at December 31, 2020 and 2019, 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;Based on our existing patents, we estimate amortization expense related to patents in each of the next five years to be the following:&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" id="z1566f0aad503425294fc597dc5e10f73" 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: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Year Ending 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;Amortization&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;(in millions)&lt;/div&gt;&lt;/td&gt;
    &lt;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;2021&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2.1&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 88%;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2022&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;2.0&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; 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;2023&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1.9&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 88%;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2024&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;1.7&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: 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;2025&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1.6&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/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 review our capitalized patent costs regularly to ensure that they include costs for patents and patent applications that have future value. When we identify patents and patent applications that we are not actively pursuing, we write off any associated costs. In 2020, 2019 and 2018, patent expenses were $4.1 million, $4.2 million and $2.6 million, respectively, and included non-cash charges related to the write-down of our patent costs to their estimated net realizable values of $1.9 million, $2.2 million and $0.8 million, respectively.&lt;/div&gt;
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      unitRef="U001">37000000.0</us-gaap:FiniteLivedIntangibleAssetsGross>
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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;Based on our existing patents, we estimate amortization expense related to patents in each of the next five years to be the following:&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" id="z1566f0aad503425294fc597dc5e10f73" 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: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Year Ending 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;Amortization&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;(in millions)&lt;/div&gt;&lt;/td&gt;
    &lt;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;2021&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2.1&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
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    &lt;td style="vertical-align: bottom; width: 88%;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2022&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;2.0&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; 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;2023&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1.9&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 88%;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2024&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;1.7&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: 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;2025&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1.6&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
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&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Our accrued liabilities consisted of the following (in thousands):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" id="zc442150657ce4320af53f69853dbac04" 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;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/&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;2020&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2019&lt;/div&gt;&lt;/td&gt;
    &lt;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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;39,477&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;24,461&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #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;8,264&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;10,289&lt;/div&gt;&lt;/td&gt;
    &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;11,559&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;6,020&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #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;30,861&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;25,999&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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;90,161&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;66,769&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;
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&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Noncontrolling Interest in Akcea Therapeutics, Inc.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Since Akcea&#x2019;s IPO in July 2017 and prior to the Akcea Acquisition in October 2020, the shares of Akcea&#x2019;s common stock third parties owned represented an interest in Akcea&#x2019;s equity that we did not control. During this period our ownership ranged from &lt;/span&gt;68 percent&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; to &lt;/span&gt;77 percent&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;. However, as we maintained overall control of Akcea through our voting interest, we reflected the assets, liabilities and results of operations of Akcea in our consolidated financial statements. Since Akcea&#x2019;s IPO in July 2017 and through the closing of the Akcea Acquisition, we reflected the noncontrolling interest attributable to other owners of Akcea&#x2019;s common stock on a separate line on our statement of operations and a separate line within stockholders&#x2019; equity in our consolidated balance sheet. In addition, through the closing of the Akcea Acquisition, we recorded a noncontrolling interest adjustment to account for the stock options Akcea granted, which if exercised, would have diluted our ownership in Akcea. This adjustment was a reclassification within stockholders&#x2019; equity from additional paid-in capital to noncontrolling interest in Akcea equal to the amount of stock-based compensation expense Akcea had recognized. Additionally, w&lt;/span&gt;e reflected changes in our ownership percentage in our financial statements as an adjustment to noncontrolling interest in the period the change occurred.&lt;/div&gt;
</us-gaap:ConsolidationSubsidiariesOrOtherInvestmentsConsolidatedEntitiesPolicy>
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    <us-gaap:ConcentrationRiskCreditRisk
      contextRef="c20200101to20201231"
      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:InvestmentPolicyTextBlock
      contextRef="c20200101to20201231"
      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 statement of operations. We use the specific identification method to determine the cost of securities sold.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We also have equity investments of less than 20 percent ownership in publicly and privately held biotechnology companies that we received as part of a technology license or partner agreement. At December 31, 2020, we held equity investments in two publicly held companies, ProQR Therapeutics N.V., or ProQR, and Antisense Therapeutics Limited, or ATL. We also held equity investments in seven privately-held companies, Aro Biotherapeutics, Atlantic Pharmaceuticals Limited, Dynacure SAS, Empirico, Inc., Flamingo Therapeutics BV, Seventh Sense Biosystems and Suzhou-Ribo Life Science Co, Ltd.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&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 statement of operations. We account for our equity investments in privately held companies at their cost minus impairments, plus or minus changes resulting from observable price changes in orderly transactions for the identical or similar investment of the same issuer. For example, &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;during the second and fourth quarters of 2020, we revalued our investments in &lt;/span&gt;three&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; privately held companies, Dynacure, Suzhou-Ribo and Aro Biotherapeutics because the companies sold additional equity securities that were similar to the equity we own. These observable price changes resulted in us recognizing a $&lt;/span&gt;6.3&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million gain on our investment in Dynacure, a $&lt;/span&gt;3.0&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million gain on our investment in Suzhou-Ribo and a $&lt;/span&gt;5.5&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million gain on our investment in Aro Biotherapeutics in our consolidated statement of operations during 2020 because the sales were at higher prices compared to our recorded value.&lt;/span&gt;&lt;/div&gt;
</us-gaap:InvestmentPolicyTextBlock>
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      unitRef="U007">7</ions:NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment>
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      contextRef="c20200401to20200630_FinancialInstrumentAxis_DynacureSasMember"
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      unitRef="U001">6300000</us-gaap:GainLossOnInvestments>
    <us-gaap:GainLossOnInvestments
      contextRef="c20201001to20201231_FinancialInstrumentAxis_SuzhouRiboLifeScienceCoLtdMember"
      decimals="-5"
      id="Fact_47b16f5d19a84a8c9a09fbbe96174527"
      unitRef="U001">3000000.0</us-gaap:GainLossOnInvestments>
    <us-gaap:GainLossOnInvestments
      contextRef="c20201001to20201231_FinancialInstrumentAxis_AroBiotherapeuticsMember"
      decimals="-5"
      id="Fact_cf49d586d5334999834bf4a673cb3dfa"
      unitRef="U001">5500000</us-gaap:GainLossOnInvestments>
    <us-gaap:InventoryPolicyTextBlock
      contextRef="c20200101to20201231"
      id="Text_962b0a89596444369c91918399edde59">
&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Inventory Valuation&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&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 on our consolidated balance sheet 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.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&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 obtained the first regulatory approval for TEGSEDI in July 2018 and for WAYLIVRA in May 2019. At December 31, 2020, our physical inventory for TEGSEDI and WAYLIVRA included API that we produced prior to when we obtained regulatory approval. As such, this API has no cost basis as we had previously expensed the costs as R&amp;amp;D expenses.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We 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. We recorded an &lt;span style="-sec-ix-hidden:Fact_b86d72920caa47448f2abd7be8e5c180"&gt;&lt;span style="-sec-ix-hidden:Fact_1261d93c836d4d94bba4bd8c45f1e569"&gt;insignificant&lt;/span&gt;&lt;/span&gt; amount of inventory write-offs during the years ended December 31, 2020 and 2019. We did not record any inventory write-offs for the year ended December 31, 2018.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;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" id="z420cf186c4154a629acd33b8e4e537ba" 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;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/&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;2020&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2019&lt;/div&gt;&lt;/td&gt;
    &lt;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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;9,206&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;9,363&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #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;7,502&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;6,520&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;16,708&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;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;15,883&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 76%;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Work in process&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2,252&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: 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;2,039&lt;/div&gt;&lt;/td&gt;
    &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;3,005&lt;/div&gt;&lt;/td&gt;
    &lt;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;258&lt;/div&gt;&lt;/td&gt;
    &lt;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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;21,965&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;18,180&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;
</us-gaap:InventoryPolicyTextBlock>
    <us-gaap:InventoryWriteDown
      contextRef="c20180101to20181231"
      decimals="-3"
      id="Fact_4bf69ae4679448c7a37b15f378b51ee0"
      unitRef="U001">0</us-gaap:InventoryWriteDown>
    <us-gaap:ScheduleOfInventoryCurrentTableTextBlock
      contextRef="c20200101to20201231"
      id="Text_42918dc083b14298bf3e140fca4a1e1b">
&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Our inventory consisted of the following (in thousands):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" id="z420cf186c4154a629acd33b8e4e537ba" 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;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/&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;2020&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2019&lt;/div&gt;&lt;/td&gt;
    &lt;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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;9,206&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;9,363&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #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;7,502&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;6,520&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;16,708&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;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;15,883&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 76%;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Work in process&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2,252&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: 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;2,039&lt;/div&gt;&lt;/td&gt;
    &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;3,005&lt;/div&gt;&lt;/td&gt;
    &lt;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;258&lt;/div&gt;&lt;/td&gt;
    &lt;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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;21,965&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;18,180&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="c20201231_PublicUtilitiesInventoryAxis_ClinicalRawMaterialsMember"
      decimals="-3"
      id="Fact_607597dd540146e09e590486dfbfd332"
      unitRef="U001">9206000</us-gaap:InventoryRawMaterials>
    <us-gaap:InventoryRawMaterials
      contextRef="c20191231_PublicUtilitiesInventoryAxis_ClinicalRawMaterialsMember"
      decimals="-3"
      id="Fact_7cb2d5b100c4460fa603ceb958dfa363"
      unitRef="U001">9363000</us-gaap:InventoryRawMaterials>
    <us-gaap:InventoryRawMaterials
      contextRef="c20201231_PublicUtilitiesInventoryAxis_CommercialRawMaterialsMember"
      decimals="-3"
      id="Fact_7ce8ae9ab80f4c6b893833f04a2e1b3a"
      unitRef="U001">7502000</us-gaap:InventoryRawMaterials>
    <us-gaap:InventoryRawMaterials
      contextRef="c20191231_PublicUtilitiesInventoryAxis_CommercialRawMaterialsMember"
      decimals="-3"
      id="Fact_de29fe59994e4eedaaf0e505fe2fa8ce"
      unitRef="U001">6520000</us-gaap:InventoryRawMaterials>
    <us-gaap:InventoryRawMaterials
      contextRef="c20201231"
      decimals="-3"
      id="Fact_128d62d036e2429290b412a68bb359e3"
      unitRef="U001">16708000</us-gaap:InventoryRawMaterials>
    <us-gaap:InventoryRawMaterials
      contextRef="c20191231"
      decimals="-3"
      id="Fact_2a47aa942a2943ed97036570c8b25890"
      unitRef="U001">15883000</us-gaap:InventoryRawMaterials>
    <us-gaap:InventoryWorkInProcess
      contextRef="c20201231"
      decimals="-3"
      id="Fact_85d7f4970a574d26939ed8575266e7f1"
      unitRef="U001">2252000</us-gaap:InventoryWorkInProcess>
    <us-gaap:InventoryWorkInProcess
      contextRef="c20191231"
      decimals="-3"
      id="Fact_84044948dea84b95bf0906aa87b24ba3"
      unitRef="U001">2039000</us-gaap:InventoryWorkInProcess>
    <us-gaap:InventoryFinishedGoods
      contextRef="c20201231"
      decimals="-3"
      id="Fact_e5ad76dbdb1441b68871a7035a59c0b3"
      unitRef="U001">3005000</us-gaap:InventoryFinishedGoods>
    <us-gaap:InventoryFinishedGoods
      contextRef="c20191231"
      decimals="-3"
      id="Fact_518f7488f3314fafb99fe4a5c96254f0"
      unitRef="U001">258000</us-gaap:InventoryFinishedGoods>
    <us-gaap:InventoryNet
      contextRef="c20201231"
      decimals="-3"
      id="Fact_ed1f9a6ae98d4c7cba25f90cb15577f3"
      unitRef="U001">21965000</us-gaap:InventoryNet>
    <us-gaap:InventoryNet
      contextRef="c20191231"
      decimals="-3"
      id="Fact_d2b4370b0072452b9c9faa8459b51794"
      unitRef="U001">18180000</us-gaap:InventoryNet>
    <us-gaap:PropertyPlantAndEquipmentPolicyTextBlock
      contextRef="c20200101to20201231"
      id="Text_cdabff15346b44629390c82abd47c849">
&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Property, Plant and Equipment&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We carry our property, plant and equipment at cost and depreciate it on the straight-line method over its estimated useful life, which consists of the following (in thousands):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" id="z0d198c5954a847b59f5bfeab5aaeb505" 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;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/&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;Estimated Useful Lives&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;December 31,&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;(in years)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2020&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2019&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Computer software, laboratory, manufacturing and other equipment&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;3 to 10&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;68,990&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;60,965&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;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Building, building improvements and building systems&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;15 to 40&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;137,879&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;119,830&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Land improvements&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;20&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;8,391&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2,853&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Leasehold improvements&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;5 to 15&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;17,263&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;13,600&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Furniture and fixtures&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;5 to 10&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;12,871&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;7,354&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 64%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;245,394&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: 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;204,602&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Less accumulated depreciation&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(87,379&lt;/div&gt;&lt;/td&gt;
    &lt;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;(74,013&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 64%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;158,015&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#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;130,589&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Land&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;23,062&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;23,062&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 64%; padding-bottom: 4px;" valign="bottom"&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#160;Total&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;181,077&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;153,651&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We depreciate our leasehold improvements using the shorter of the estimated useful life or remaining lease term.&lt;/div&gt;
</us-gaap:PropertyPlantAndEquipmentPolicyTextBlock>
    <us-gaap:PropertyPlantAndEquipmentTextBlock
      contextRef="c20200101to20201231"
      id="Text_fa1490903d3d4bf4a66e00ec0646e2ed">
&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We carry our property, plant and equipment at cost and depreciate it on the straight-line method over its estimated useful life, which consists of the following (in thousands):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" id="z0d198c5954a847b59f5bfeab5aaeb505" 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;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/&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;Estimated Useful Lives&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;December 31,&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;(in years)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2020&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2019&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Computer software, laboratory, manufacturing and other equipment&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;3 to 10&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;68,990&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;60,965&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;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Building, building improvements and building systems&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;15 to 40&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;137,879&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;119,830&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Land improvements&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;20&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;8,391&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2,853&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Leasehold improvements&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;5 to 15&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;17,263&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;13,600&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Furniture and fixtures&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;5 to 10&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;12,871&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;7,354&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 64%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;245,394&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: 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;204,602&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Less accumulated depreciation&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(87,379&lt;/div&gt;&lt;/td&gt;
    &lt;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;(74,013&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 64%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
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    &lt;td colspan="1" style="text-align: 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;130,589&lt;/div&gt;&lt;/td&gt;
    &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;
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    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
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    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;23,062&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 64%; padding-bottom: 4px;" valign="bottom"&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#160;Total&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;181,077&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;153,651&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
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    <us-gaap:FairValueOfFinancialInstrumentsPolicy
      contextRef="c20200101to20201231"
      id="Text_1c1a3fa5b06c4f8eb0d08a8a2d8e1c26">
&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Fair Value of Financial Instruments&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; &lt;/span&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We have estimated the fair value of our financial instruments. The amounts reported for cash, accounts receivable, accounts payable and accrued expenses approximate the fair value because of their short maturities. We report our investment securities at their estimated fair value based on quoted market prices for identical or similar instruments.&lt;/div&gt;
</us-gaap:FairValueOfFinancialInstrumentsPolicy>
    <us-gaap:LesseeLeasesPolicyTextBlock
      contextRef="c20200101to20201231"
      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 on our consolidated balance sheet 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 concluded we were reasonably certain that we will 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 current leases do not provide an interest rate implicit in the lease, we used our incremental borrowing rate, based on the information available on the date we adopted Topic 842 (January 2019), 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. 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:ImpairmentOrDisposalOfLongLivedAssetsIncludingIntangibleAssetsPolicyPolicyTextBlock
      contextRef="c20200101to20201231"
      id="Text_72f861d09ee741518162baaf74392e58">
&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Long-Lived Assets&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; &lt;/span&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We evaluate long-lived assets, which include property, plant and equipment and patent costs, 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. We recorded charges of $1.9 million, $2.2 million and $0.8 million for the years ended December 31, 2020, 2019 and 2018, respectively, related to the write-down of patents.&lt;/div&gt;
</us-gaap:ImpairmentOrDisposalOfLongLivedAssetsIncludingIntangibleAssetsPolicyPolicyTextBlock>
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      decimals="-5"
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    <us-gaap:UseOfEstimates
      contextRef="c20200101to20201231"
      id="Text_0a3950b68c174b56bc1921a8ef188db5">
&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;The preparation of consolidated financial statements in conformity with accounting principles generally accepted in the U.S. requires management to make estimates and assumptions that affect the amounts reported in the consolidated financial statements and accompanying notes. Actual results could differ from those estimates.&lt;/div&gt;
</us-gaap:UseOfEstimates>
    <us-gaap:ShareBasedCompensationOptionAndIncentivePlansPolicy
      contextRef="c20200101to20201231"
      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, 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 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. We estimate the expected term of options granted based on 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;We recognize compensation expense for option awards and RSUs 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;"&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 vest annually over a four-year period. RSUs granted after June 2020 to our board of directors vest annually.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;See Note 4, &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Stockholders&#x2019; Equity,&lt;/span&gt; for additional information regarding our stock-based compensation plans.&lt;/div&gt;
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&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Accumulated Other Comprehensive Loss&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Accumulated other comprehensive loss is comprised of unrealized gains and losses on investments, net of taxes and currency translation adjustments. The following table summarizes changes in accumulated other comprehensive loss for the years ended December 31, &lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;2020&lt;/span&gt;&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;"&gt;2019&lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; and &lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;2018&lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; (in thousands):&lt;/span&gt;&lt;/div&gt;

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

&lt;table cellpadding="0" cellspacing="0" id="z0f84e575a1a8436991d62963b2899dd6" 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;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/&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;2020&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2019&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; 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;2018&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Beginning balance accumulated other comprehensive loss&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(25,290&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(32,016&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times 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;(31,759&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 64%;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Unrealized gains (losses) on securities, net of tax (1)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;3,729&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;6,633&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: 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;(280&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&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: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Currency translation adjustment&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;617&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;93&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-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;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 64%; padding-bottom: 2px;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Adjustments to other comprehensive loss from purchase of noncontrolling interest of Akcea Therapeutics, Inc.&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(127&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;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: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Net other comprehensive loss for the period&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;4,219&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #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;6,726&lt;/div&gt;&lt;/td&gt;
    &lt;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;(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;&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: 4px;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Ending balance accumulated other comprehensive loss&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(21,071&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(25,290&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(32,016&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;________________&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z9ecfa3f5cf504526a0786f25593849bf" 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; align: right;"&gt;&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(1)&lt;/div&gt;&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top;"&gt;&lt;div style="text-align: justify; text-indent: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We did not have tax expense included in our other comprehensive loss for the year ended December 31, 2020. For the years ended December 31, 2019 and 2018, we had a tax benefit $1.4 million and $0.3 million included in other comprehensive loss respectively.&#160;&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
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    <us-gaap:ScheduleOfAccumulatedOtherComprehensiveIncomeLossTableTextBlock
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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: 12pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Accumulated other comprehensive loss is comprised of unrealized gains and losses on investments, net of taxes and currency translation adjustments. The following table summarizes changes in accumulated other comprehensive loss for the years ended December 31, &lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;2020&lt;/span&gt;&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;"&gt;2019&lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; and &lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;2018&lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; (in thousands):&lt;/span&gt;&lt;/div&gt;

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

&lt;table cellpadding="0" cellspacing="0" id="z0f84e575a1a8436991d62963b2899dd6" 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;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/&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;2020&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2019&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; 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;2018&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Beginning balance accumulated other comprehensive loss&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(25,290&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(32,016&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times 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;(31,759&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 64%;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Unrealized gains (losses) on securities, net of tax (1)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;3,729&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;6,633&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: 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;(280&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&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: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Currency translation adjustment&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;617&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;93&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-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;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 64%; padding-bottom: 2px;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Adjustments to other comprehensive loss from purchase of noncontrolling interest of Akcea Therapeutics, Inc.&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(127&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;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: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Net other comprehensive loss for the period&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;4,219&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #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;6,726&lt;/div&gt;&lt;/td&gt;
    &lt;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;(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;&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: 4px;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Ending balance accumulated other comprehensive loss&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(21,071&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(25,290&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(32,016&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;________________&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z9ecfa3f5cf504526a0786f25593849bf" 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; align: right;"&gt;&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(1)&lt;/div&gt;&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top;"&gt;&lt;div style="text-align: justify; text-indent: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We did not have tax expense included in our other comprehensive loss for the year ended December 31, 2020. For the years ended December 31, 2019 and 2018, we had a tax benefit $1.4 million and $0.3 million included in other comprehensive loss respectively.&#160;&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;
</us-gaap:ScheduleOfAccumulatedOtherComprehensiveIncomeLossTableTextBlock>
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&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;At issuance, we accounted for our convertible debt instruments, including our 0.125 percent senior convertible notes, or 0.125% Notes, and 1 percent senior convertible notes, or 1% Notes, that may be settled in cash upon conversion (including partial cash settlement) by separating the liability and equity components of the instruments in a manner that reflects our nonconvertible debt borrowing rate on the date the notes were issued. In reviewing debt issuances, we were not able to identify any comparable companies that issued non-convertible debt instruments at the time of the issuance of the convertible notes. Therefore, we estimated the fair value of the liability component of our notes by using assumptions that market participants would use in pricing a debt instrument, including market interest rates, credit standing, yield curves and volatilities.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&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 assigned a value to the debt component of our convertible notes equal to the estimated fair value of similar debt instruments without the conversion feature, which resulted in us recording our debt at a discount. We are amortizing our debt issuance costs and debt discount over the life of the convertible notes as additional non-cash interest expense utilizing the effective interest method. For additional information, see Note 3, &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;.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&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% Notes mature in November 2021. Therefore, as of December 31, 2020, we classified the liability component of the 1% Notes as a current liability on our consolidated balance sheet.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&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 2020, the FASB issued guidance simplifying the accounting for convertible debt instruments. See the section titled &#x201c;Impact of Recently Issued Accounting Standards&#x201d; below for details.&lt;/div&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;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 0.125% Notes, we entered into a call spread transaction, which was 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 Derivatives and Hedging &#x2013; Contracts in Entity&#x2019;s Own Equity 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 sheet. We reassess our ability to continue to classify the note hedges and warrants in shareholders&#x2019; equity at each reporting period.&lt;/div&gt;
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    <us-gaap:SegmentReportingPolicyPolicyTextBlock
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&lt;div style="text-align: justify; 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;Through 2020, we had two operating segments, our Ionis Core segment and Akcea Therapeutics. &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Akcea was focused on developing and commercializing medicines to treat patients with serious and rare diseases. We have provided segment financial information and results for our Ionis Core segment and our Akcea Therapeutics segment based on the segregation of revenues and expenses that our chief decision maker reviewed to assess operating performance and to make operating decisions through 2020. We allocated a portion of Ionis&#x2019; development, R&amp;amp;D support and general and administrative expenses to Akcea for work Ionis performed on behalf of Akcea and we billed Akcea for these expenses.&lt;/span&gt;&lt;/div&gt;
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    <us-gaap:FairValueMeasurementPolicyPolicyTextBlock
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&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 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 held biotechnology companies; Level 2, defined as inputs other than quoted prices in active markets that are either directly or indirectly observable, which includes our fixed income securities and commercial paper classified as available-for-sale securities; and Level 3, defined as unobservable inputs in which little or no market data exists, therefore requiring us to develop our own assumptions. We classify most of our securities as Level 2. We obtain the fair value of our Level 2 investments from our custodian bank or from a professional pricing service. We validate the fair value of our Level 2 investments by understanding the pricing model used by the custodian banks or professional pricing service provider and comparing that fair value to the fair value based on observable market prices.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The following tables present the major security types we held at December 31, 2020 and 2019&#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;. At December 31, 2019, our ProQR investment was &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;subject to trading restrictions until the fourth quarter of 2020, as a result we&lt;/span&gt; included a lack of marketability discount in valuing this investment, which is a Level 3 input. As of December 31, 2020, our ProQR investment was no longer subject to trading restrictions. As of December 31, 2020, we did not have any investments which we valued using Level 3 inputs. The following tables segregate each security type by the level within the fair value hierarchy of the valuation techniques we utilized to determine the respective securities&#x2019; fair value (in thousands):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

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    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 8pt;"/&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;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, 2020&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Quoted Prices in&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Active Markets&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;(Level 1)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Significant Other&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Observable Inputs&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;(Level 2)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
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    &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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;221,125&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;221,125&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-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;846,315&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: 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;846,315&lt;/div&gt;&lt;/td&gt;
    &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 (4)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;174,861&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;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;174,861&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;/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;358,497&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: 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;358,497&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: 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 (4)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;136,309&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-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;136,309&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #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 (4)&lt;/div&gt;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;6,225&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;6,225&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#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;Investment in ProQR Therapeutics N.V. (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;2,031&lt;/div&gt;&lt;/td&gt;
    &lt;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;2,031&lt;/div&gt;&lt;/td&gt;
    &lt;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;1,745,363&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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;581,653&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;1,163,710&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" id="z42641d00b2bd400e81caba6eddf342f0" 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="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;At&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;December 31, 2019&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; 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;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;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Significant Other&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Observable Inputs&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;(Level 2)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Significant&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Unobservable Inputs&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;(Level 3)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Cash equivalents (1)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;418,406&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;418,406&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Corporate debt securities (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;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,102,568&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: 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;1,102,568&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by U.S. government agencies (7)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;329,404&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-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;329,404&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by the U.S. Treasury (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;363,694&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: 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;363,694&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by states of the U.S. and political subdivisions of the states (4)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;40,407&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-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;40,407&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; 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;Investment in ProQR Therapeutics N.V. (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;4,506&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;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;4,506&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: 52%; 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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2,258,985&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;782,100&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,472,379&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;4,506&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" id="z791574a09f2444c599172d57b45fe997" 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; vertical-align: top; align: right; 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 on our consolidated balance sheet.&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" id="za3c5f136d4254206a5ec01a41ea4efb9" 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; vertical-align: top; align: right; 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;$10.0 million included in cash and cash equivalents on our consolidated balance sheet, with the difference included in short-term investments on our consolidated balance sheet.&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" id="z148638abbe4544afb1bfb13a3a3df99e" 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; vertical-align: top; align: right; 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;$17.5 million included in cash and cash equivalents on our consolidated balance sheet, with the difference included in short-term investments on our consolidated balance sheet.&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" id="zfe5f26749b614dbcb042f4c2f2ba5a12" 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; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(4)&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Included in short-term investments.&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z7c2aa671a6d84170836be6a95eff7f0e" 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; vertical-align: top; align: right; 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 on our consolidated balance sheet.&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" id="zae152b0de27346b784a63d2fad55dc16" 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; vertical-align: top; align: right; 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;$19.0 million included in cash and cash equivalents on our consolidated balance sheet, with the difference included in short-term investments on our consolidated balance sheet.&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" id="z13ffd34009fd4d8ea5be9d956bd94c78" 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; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(7)&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;$0.8 million included in cash and cash equivalents on our consolidated balance sheet, with the difference included in short-term investments on our consolidated balance sheet.&#160; &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;The following tables present the major security types we held at December 31, 2020 and 2019&#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;. At December 31, 2019, our ProQR investment was &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;subject to trading restrictions until the fourth quarter of 2020, as a result we&lt;/span&gt; included a lack of marketability discount in valuing this investment, which is a Level 3 input. As of December 31, 2020, our ProQR investment was no longer subject to trading restrictions. As of December 31, 2020, we did not have any investments which we valued using Level 3 inputs. The following tables segregate each security type by the level within the fair value hierarchy of the valuation techniques we utilized to determine the respective securities&#x2019; fair value (in thousands):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" id="z6070756b157447b980511cdf4857d355" 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;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 8pt;"/&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;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, 2020&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Quoted Prices in&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Active Markets&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;(Level 1)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Significant Other&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Observable Inputs&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;(Level 2)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Cash equivalents (1)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;221,125&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;221,125&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-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;846,315&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: 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;846,315&lt;/div&gt;&lt;/td&gt;
    &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 (4)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;174,861&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;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;174,861&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;/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;358,497&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: 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;358,497&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: 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 (4)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;136,309&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-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;136,309&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #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 (4)&lt;/div&gt;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;6,225&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;6,225&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#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;Investment in ProQR Therapeutics N.V. (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;2,031&lt;/div&gt;&lt;/td&gt;
    &lt;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;2,031&lt;/div&gt;&lt;/td&gt;
    &lt;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;1,745,363&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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;581,653&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;1,163,710&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" id="z42641d00b2bd400e81caba6eddf342f0" 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="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;At&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;December 31, 2019&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; 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;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;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Significant Other&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Observable Inputs&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;(Level 2)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Significant&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Unobservable Inputs&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;(Level 3)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Cash equivalents (1)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;418,406&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;418,406&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Corporate debt securities (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;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,102,568&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: 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;1,102,568&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by U.S. government agencies (7)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;329,404&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-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;329,404&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by the U.S. Treasury (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;363,694&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: 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;363,694&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by states of the U.S. and political subdivisions of the states (4)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;40,407&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-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;40,407&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-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;
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    &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;
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    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
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    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;4,506&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;
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    &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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2,258,985&lt;/div&gt;&lt;/td&gt;
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    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;782,100&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,472,379&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;4,506&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;

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    &lt;td style="width: 36pt; vertical-align: top; align: right; 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 on our consolidated balance sheet.&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
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&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="za3c5f136d4254206a5ec01a41ea4efb9" 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;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;$10.0 million included in cash and cash equivalents on our consolidated balance sheet, with the difference included in short-term investments on our consolidated balance sheet.&lt;/div&gt;&lt;/td&gt;
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&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

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    &lt;td style="width: 36pt; vertical-align: top; align: right; 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;$17.5 million included in cash and cash equivalents on our consolidated balance sheet, with the difference included in short-term investments on our consolidated balance sheet.&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
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&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="zfe5f26749b614dbcb042f4c2f2ba5a12" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
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&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z7c2aa671a6d84170836be6a95eff7f0e" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
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    &lt;td style="width: 36pt; vertical-align: top; align: right; 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 on our consolidated balance sheet.&lt;/div&gt;&lt;/td&gt;
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&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

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  &lt;tr&gt;
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    &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;$19.0 million included in cash and cash equivalents on our consolidated balance sheet, with the difference included in short-term investments on our consolidated balance sheet.&lt;/div&gt;&lt;/td&gt;
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&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

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  &lt;tr&gt;
    &lt;td style="width: 36pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(7)&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;$0.8 million included in cash and cash equivalents on our consolidated balance sheet, with the difference included in short-term investments on our consolidated balance sheet.&#160; &lt;/div&gt;&lt;/td&gt;
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&lt;/table&gt;
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    <us-gaap:IncomeTaxPolicyTextBlock
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      id="Text_ea1db2e5fbf346468e0ca231e0179de4">
&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, no assurance can be given that the final tax outcome of these matters will not be different from that which is 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 such determination is made.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&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.&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; 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;/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 do not provide for a U.S. income tax liability and foreign withholding taxes on undistributed foreign earnings of our foreign subsidiaries.&lt;/div&gt;
</us-gaap:IncomeTaxPolicyTextBlock>
    <us-gaap:NewAccountingPronouncementsPolicyPolicyTextBlock
      contextRef="c20200101to20201231"
      id="Text_3dc0dd1b880c4ca0996def0810117ca8">
&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Impact of 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 June 2016, the FASB issued guidance that changes the measurement of credit losses for most financial assets and certain other instruments. If we have credit losses, this updated guidance requires us to record allowances for these instruments under a new expected credit loss model. This model requires us to estimate the expected credit loss of an instrument over its lifetime, which represents the portion of the amortized cost basis we do not expect to collect. The new guidance requires us to remeasure our allowance in each reporting period we have credit losses. We adopted this new guidance on January 1, 2020. This guidance did not have an impact on our consolidated financial statements.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In August 2018, the FASB issued clarifying guidance on how to account for implementation costs related to cloud-servicing arrangements. The guidance states that if these fees qualify to be capitalized and amortized over the service period, they need to be expensed in the same line item as the service expense and recognized in the same balance sheet category. The update can be applied either retrospectively or prospectively to all implementation costs incurred after the date of adoption. We adopted this guidance on January 1, 2020 on a prospective basis. This guidance did not have an impact on our consolidated financial statements.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In November 2018, the FASB issued clarifying guidance of the interaction between the collaboration accounting guidance and the new revenue recognition guidance we adopted on January 1, 2018 (Topic 606). Below is the clarifying guidance and how we implemented it (in italics):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="zf1701d3f1d8d4160978d38fc5e5b4c66" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; 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;When a participant is considered a customer in a collaborative arrangement, all of the associated accounting under Topic 606 should be applied.&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z3d884347466d4766902ab98141f40262" 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: 72pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&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; font-style: italic;"&gt;We are applying all of the associated accounting under Topic 606 when we determine a participant in a collaborative arrangement is a customer.&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="zbefb18546da74bf487f114918d77add3" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; 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;Adds &#x201c;unit of account&#x201d; concept to collaboration accounting guidance to align with Topic 606. The &#x201c;unit of account&#x201d; concept is used to determine if revenue is recognized or if a contra expense is recognized from consideration received under a collaboration.&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z28c82932c2e1414281433d5974927174" 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: 72pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&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; font-style: italic;"&gt;We use the &#x201c;unit of account&#x201d; concept when we receive consideration under a collaborative arrangement to determine when we recognize revenue or a contra expense.&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="za50af4149c204796bc74ae610430cd43" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; 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;The clarifying guidance precludes us from recognizing revenue under Topic 606 when we determine a transaction with a collaborative partner is not a customer and is not directly related to the sales to third parties.&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="zd9d21a16a5b3482c85eb10cf58a06d3e" 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: 72pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&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; font-style: italic;"&gt;When we conclude a collaboration partner is not a customer and is not directly related to the sales to third parties, we do not recognize revenue for the transaction.&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 adopted this new guidance on January 1, 2020. This guidance did not have any impact on our consolidated financial statements.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;In August 2020, the FASB issued guidance &lt;/span&gt;which simplifies the accounting for convertible instruments&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;, amends the guidance on derivative scope exceptions for contracts in an entity&#x2019;s own equity, and modifies the guidance on diluted earnings per share calculations as a result of these changes. Under our current outstanding convertible debt arrangements, we anticipate the following impacts:&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="zcbb885b9cab547a1b31cd283712248a2" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 36pt; vertical-align: top; align: right; 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;We will no longer separate our existing convertible debt into liability and equity components. Therefore, we will no longer recognize a debt discount for the value of the conversion option, instead we will record the face value of the convertible debt as a liability on our consolidated balance sheet;&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z66fb90d1a5be4351bc55d49e62d382d6" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; 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;We will record cash interest expense plus amortization of debt issuance costs to interest expense. Since we will not recognize a debt discount, we will no longer record the amortization of a debt discount to interest expense; and&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="ze1e1f5e6552b4bfc822ec7f94c42c685" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; 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;We do not expect our EPS calculation to not change under this update. We plan to continue to use the if-converted method to calculate diluted earnings per share.&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 plan to adopt this guidance in the first quarter of 2021 under the full retrospective approach, meaning we will apply the guidance to all periods presented beginning in the first quarter of 2021.&lt;/div&gt;
</us-gaap:NewAccountingPronouncementsPolicyPolicyTextBlock>
    <us-gaap:InvestmentTextBlock
      contextRef="c20200101to20201231"
      id="Text_9571e0c61df44815a452af9dc71349ef">
&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2. Investments&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The following table summarizes the contract maturity of the available-for-sale securities we held as of December 31, 2020:&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" id="zb8b331d548474cfd89ae511966ada4d1" 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;One year 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;73&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&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 one year but within two years&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;18&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
  &lt;/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 two years but within &lt;span style="-sec-ix-hidden:Fact_5b50da2d62974df399b2ebfcfccf0c30"&gt;three and a half years&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;9&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 88%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;100&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;As illustrated above, at December 31, 2020, 91 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;At December 31, 2020, we had an ownership interest of less than 20 percent &lt;span style="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;seven&lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; private companies and &lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;two&lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; public companies with which we conduct business. The privately-held companies are &lt;/span&gt;Aro Biotherapeutics, Atlantic Pharmaceuticals Limited, Dynacure SAS, Empirico, Inc., Flamingo Therapeutics BV, Seventh Sense Biosystems and Suzhou Ribo Life Science Co, Ltd. The publicly traded companies are ATL and ProQR.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&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" id="zb7472965e89a4156a0a9d32fd3eb5bf4" 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;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"/&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;&#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="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, 2020&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;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Cost &lt;/span&gt;(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;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 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 (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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;514,182&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2,194&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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(41&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;516,335&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #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;94,234&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;354&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(2&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;94,586&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 (2)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;307,576&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;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;(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;307,800&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 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;104,271&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;196&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;(12&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;104,455&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;5,191&lt;/div&gt;&lt;/td&gt;
    &lt;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;(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;&lt;div style="font-family: 'Times 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;5,184&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total securities with a maturity of one year or less&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,025,454&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;2,977&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;(71&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;1,028,360&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;325,079&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;4,941&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(40&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times 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;329,980&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #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;80,099&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;185&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;(9&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;80,275&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;50,318&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;383&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-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;&lt;div style="font-family: 'Times 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;50,697&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #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;31,779&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;91&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;(16&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;31,854&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;1,041&lt;/div&gt;&lt;/td&gt;
    &lt;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;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #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;1,041&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total securities with a maturity of 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;488,316&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;5,600&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;(69&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;493,847&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total 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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,513,770&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;8,577&lt;/div&gt;&lt;/td&gt;
    &lt;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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(140&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;1,522,207&lt;/div&gt;&lt;/td&gt;
    &lt;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;Total equity securities included in other current assets (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;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;4,712&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(2,681&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;2,031&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;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total equity securities included in deposits and other assets (4)&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;15,062&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #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;15,938&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;31,000&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total 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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;19,774&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;15,938&lt;/div&gt;&lt;/td&gt;
    &lt;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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(2,681&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;33,031&lt;/div&gt;&lt;/td&gt;
    &lt;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; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total available-for-sale and equity securities&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,533,544&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;24,515&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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(2,821&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;1,555,238&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" id="za103de634c4d4cc69d2c374dfbfb01cd" 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;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"/&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;&#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="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, 2019&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;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Cost &lt;/span&gt;(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;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 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 (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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;669,665&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,451&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(43&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;671,073&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #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;188,216&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;303&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;(43&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;188,476&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 (2)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;327,670&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;232&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(27&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times 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;327,875&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;/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;21,065&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;26&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&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;21,086&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total securities with a maturity of one year or less&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,206,616&lt;/div&gt;&lt;/td&gt;
    &lt;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;2,012&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;&#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;(118&lt;/div&gt;&lt;/td&gt;
    &lt;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;1,208,510&lt;/div&gt;&lt;/td&gt;
    &lt;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;428,627&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2,911&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;(43&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;431,495&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;140,988&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;57&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" 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%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times 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;140,928&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #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;35,822&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;9&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;(12&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;35,819&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;19,309&lt;/div&gt;&lt;/td&gt;
    &lt;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;18&lt;/div&gt;&lt;/td&gt;
    &lt;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;(6&lt;/div&gt;&lt;/td&gt;
    &lt;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;19,321&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total securities with a maturity of 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;624,746&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;2,995&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;(178&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;627,563&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total 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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,831,362&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;5,007&lt;/div&gt;&lt;/td&gt;
    &lt;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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(296&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;1,836,073&lt;/div&gt;&lt;/td&gt;
    &lt;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; 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;Total equity securities included in other current assets (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;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;4,712&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(870&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;3,842&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total equity securities included in deposits and other assets (4)&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;10,000&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;10,000&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total 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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;14,712&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;&#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;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(870&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;13,842&lt;/div&gt;&lt;/td&gt;
    &lt;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; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total available-for-sale and equity securities&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,846,074&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;5,007&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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(1,166&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;1,849,915&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 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" id="z61f6c267d21144238581ae579b649dc5" 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; vertical-align: top; align: right; 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;We hold our available-for-sale securities at amortized cost.&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" id="z79a8f59d9a7f407a9a6b439f8b61c468" 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; vertical-align: top; align: right; 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;Includes investments classified as cash equivalents on our consolidated balance sheet.&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" id="z306650d01b4d4023a6e695c9eb77db2c" 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; vertical-align: top; align: right; 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 equity securities included in other current assets consisted of our investments in publicly traded companies. We recognize publicly traded equity securities at fair value.&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" id="zc1d8531a140a4da9853ca1172a4ecfda" 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; vertical-align: top; align: right; 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;Our equity securities included in deposits and other assets consisted of our investments in privately held companies. We recognize our private company equity securities at&lt;/span&gt; cost minus impairments, plus or minus changes resulting from observable price changes in orderly transactions for the identical or similar investment of the same issuer&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; on our consolidated balance sheet.&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 &lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;following is a summary of our investments we considered to be temporarily impaired at&lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&#160;&lt;/span&gt;December 31, 2020&lt;span style="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;(in thousands). All of these investments have less than 12 months of temporary impairment. &lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&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. We believe it is more likely than not that we will be able to hold our debt securities to maturity. Therefore, we anticipate full recovery of our debt securities&#x2019; amortized cost basis at maturity.&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" id="z0c03d0d401314f14abb08017a2d22100" 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;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/&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;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;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 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;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 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: 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;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;54&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;121,162&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(81&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 64%;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 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%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-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;&#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;29,988&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: 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&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&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: 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;8&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;76,941&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(13&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 64%;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -11.2pt; margin-left: 11.2pt; 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%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;160&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: 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;49,832&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: 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;(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;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; 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;2&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&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;6,225&lt;/div&gt;&lt;/td&gt;
    &lt;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;&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: 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;Total temporarily impaired securities&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%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;284,148&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;(140&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
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</us-gaap:InvestmentTextBlock>
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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 contract maturity of the available-for-sale securities we held as of December 31, 2020:&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" id="zb8b331d548474cfd89ae511966ada4d1" 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;One year 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;73&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&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 one year but within two years&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;18&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
  &lt;/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 two years but within &lt;span style="-sec-ix-hidden:Fact_5b50da2d62974df399b2ebfcfccf0c30"&gt;three and a half years&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;9&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 88%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;100&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;
</us-gaap:InvestmentsClassifiedByContractualMaturityDateTableTextBlock>
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    <ions:MaximumContractMaturityPeriodRange2
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    <ions:AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage
      contextRef="c20201231"
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      id="Fact_54f16a3082454b16a1368f8660393627"
      unitRef="U003">0.18</ions:AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage>
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    <ions:AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeAndOneHalfYearsPercentage
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      id="Fact_d60e9c8e586b428c886b9d9653ac0f6e"
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    <ions:AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage
      contextRef="c20201231"
      decimals="2"
      id="Fact_971b070bcf6846b8970847cdbaef1457"
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      contextRef="c20200101to20201231"
      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" id="zb7472965e89a4156a0a9d32fd3eb5bf4" 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;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"/&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;&#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="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, 2020&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;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Cost &lt;/span&gt;(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;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 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 (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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;514,182&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2,194&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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(41&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;516,335&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #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;94,234&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;354&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(2&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;94,586&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 (2)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;307,576&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;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;(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;307,800&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 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;104,271&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;196&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;(12&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;104,455&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;5,191&lt;/div&gt;&lt;/td&gt;
    &lt;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;(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;&lt;div style="font-family: 'Times 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;5,184&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total securities with a maturity of one year or less&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,025,454&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;2,977&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;(71&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;1,028,360&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;325,079&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;4,941&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(40&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times 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;329,980&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #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;80,099&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;185&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;(9&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;80,275&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;50,318&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;383&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-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;&lt;div style="font-family: 'Times 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;50,697&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #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;31,779&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;91&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;(16&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;31,854&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;1,041&lt;/div&gt;&lt;/td&gt;
    &lt;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;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #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;1,041&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total securities with a maturity of 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;488,316&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;5,600&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;(69&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;493,847&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total 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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,513,770&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;8,577&lt;/div&gt;&lt;/td&gt;
    &lt;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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(140&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;1,522,207&lt;/div&gt;&lt;/td&gt;
    &lt;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;Total equity securities included in other current assets (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;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;4,712&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(2,681&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;2,031&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;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total equity securities included in deposits and other assets (4)&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;15,062&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #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;15,938&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;31,000&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total 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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;19,774&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;15,938&lt;/div&gt;&lt;/td&gt;
    &lt;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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(2,681&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;33,031&lt;/div&gt;&lt;/td&gt;
    &lt;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; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total available-for-sale and equity securities&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,533,544&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;24,515&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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(2,821&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;1,555,238&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" id="za103de634c4d4cc69d2c374dfbfb01cd" 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;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"/&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;&#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="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, 2019&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;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Cost &lt;/span&gt;(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;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 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 (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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;669,665&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,451&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(43&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;671,073&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #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;188,216&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;303&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;(43&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;188,476&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 (2)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;327,670&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;232&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(27&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times 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;327,875&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;/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;21,065&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;26&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&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;21,086&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total securities with a maturity of one year or less&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,206,616&lt;/div&gt;&lt;/td&gt;
    &lt;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;2,012&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;&#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;(118&lt;/div&gt;&lt;/td&gt;
    &lt;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;1,208,510&lt;/div&gt;&lt;/td&gt;
    &lt;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;428,627&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2,911&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;(43&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;431,495&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;140,988&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;57&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" 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%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times 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;140,928&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #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;35,822&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;9&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;(12&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;35,819&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;19,309&lt;/div&gt;&lt;/td&gt;
    &lt;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;18&lt;/div&gt;&lt;/td&gt;
    &lt;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;(6&lt;/div&gt;&lt;/td&gt;
    &lt;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;19,321&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total securities with a maturity of 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;624,746&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;2,995&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;(178&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;627,563&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total 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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,831,362&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;5,007&lt;/div&gt;&lt;/td&gt;
    &lt;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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(296&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;1,836,073&lt;/div&gt;&lt;/td&gt;
    &lt;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; 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;Total equity securities included in other current assets (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;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;4,712&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(870&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;3,842&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total equity securities included in deposits and other assets (4)&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;10,000&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;10,000&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;
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  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total equity securities&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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;14,712&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;&#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;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(870&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;13,842&lt;/div&gt;&lt;/td&gt;
    &lt;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; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total available-for-sale and equity securities&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,846,074&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;5,007&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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(1,166&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;1,849,915&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 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" id="z61f6c267d21144238581ae579b649dc5" 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; vertical-align: top; align: right; 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;We hold our available-for-sale securities at amortized cost.&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" id="z79a8f59d9a7f407a9a6b439f8b61c468" 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; vertical-align: top; align: right; 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;Includes investments classified as cash equivalents on our consolidated balance sheet.&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" id="z306650d01b4d4023a6e695c9eb77db2c" 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; vertical-align: top; align: right; 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 equity securities included in other current assets consisted of our investments in publicly traded companies. We recognize publicly traded equity securities at fair value.&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" id="zc1d8531a140a4da9853ca1172a4ecfda" 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; vertical-align: top; align: right; 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;Our equity securities included in deposits and other assets consisted of our investments in privately held companies. We recognize our private company equity securities at&lt;/span&gt; cost minus impairments, plus or minus changes resulting from observable price changes in orderly transactions for the identical or similar investment of the same issuer&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; on our consolidated balance sheet.&lt;/span&gt;&lt;/div&gt;&lt;/td&gt;
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&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;The &lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;following is a summary of our investments we considered to be temporarily impaired at&lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&#160;&lt;/span&gt;December 31, 2020&lt;span style="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;(in thousands). All of these investments have less than 12 months of temporary impairment. &lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&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. We believe it is more likely than not that we will be able to hold our debt securities to maturity. Therefore, we anticipate full recovery of our debt securities&#x2019; amortized cost basis at maturity.&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

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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;54&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
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    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(81&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 64%;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 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%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-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;&#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;29,988&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: 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&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&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;
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    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;8&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;76,941&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(13&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&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;
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    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;160&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: 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;49,832&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: 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;(28&lt;/div&gt;&lt;/td&gt;
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  &lt;/tr&gt;
  &lt;tr&gt;
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    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#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;6,225&lt;/div&gt;&lt;/td&gt;
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    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #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;&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;
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    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&#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%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;284,148&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;(140&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
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&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;3. 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" id="z491d0b86fdec4ab1bf93c193d82169f5" 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;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/&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;
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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;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2020&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2019&lt;/div&gt;&lt;/td&gt;
    &lt;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;0.125 percent 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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;455,719&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;434,711&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #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;1 percent convertible senior notes (1)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;293,161&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: 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;275,333&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Long-term mortgage debt&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;59,984&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;59,913&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;/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;Leases and other obligations&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;30,710&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;17,569&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%; 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&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;839,574&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;787,526&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; 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;Less: current portion (1)&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;(300,462&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;&lt;div style="font-family: 'Times 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;(2,026&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: 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; background-color: #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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;539,112&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;785,500&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" id="za3bbe36629904c01b690cbe109c76d9b" 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; vertical-align: top; align: right; 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;We classified the carrying value of our 1% Notes as a current liability on our consolidated balance sheet at December 31, 2020 because it matures in November 2021.&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&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;Convertible 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: left; 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;0.125 Percent&lt;/span&gt;&lt;span style="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; font-style: italic;"&gt;Convertible Senior Notes&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 December 2019, we entered into privately negotiated exchange and/or subscription agreements with certain new investors and certain holders of our existing &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;1%&lt;/span&gt; Notes to exchange $375.6 million of our &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;1%&lt;/span&gt; Notes for $439.3&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&#160;&lt;/span&gt;million of our 0.125% Notes, and to issue $109.5 million of our 0.125% Notes. We completed this exchange to reduce our cash interest payments, increase our conversion price and extend our maturity for a large portion of our debt. Additionally, i&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;n conjunction with the December 2019 exchange, 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&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; by increasing the effective conversion price even further.&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;Interest is payable semi-annually on June 15 and December 15 of each year for the &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;0.125%&lt;/span&gt; Notes. The &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;0.125%&lt;/span&gt; Notes are convertible at the option of the note holders prior to August 1, 2024 only under certain conditions. On or after August 1, 2024, the &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;0.125%&lt;/span&gt; Notes are initially convertible into approximately 6.6 million shares of common stock at a conversion price of approximately $83.28 per share. We will 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 &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;0.125%&lt;/span&gt; Notes prior to maturity, and no sinking fund is provided for them. If we undergo a fundamental change, holders may require us to purchase for cash all or any portion of their &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;0.125%&lt;/span&gt; Notes at a purchase price equal to 100 percent of the principal amount of the notes to be purchased, plus accrued and unpaid interest to, but excluding, the fundamental change purchase 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;At December 31, 2020, we had the following &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;0.125%&lt;/span&gt; Notes outstanding (amounts in millions except price per share data):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" id="zd6b190b45e7940aebc9709e23b39ca57" 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; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/&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;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;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; white-space: nowrap;" 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; 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;548.8&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; white-space: nowrap;" 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; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: top;" valign="bottom"&gt;&lt;div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;December 15, 2024&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 88%; background-color: #CCEEFF; white-space: nowrap;" 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%; 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;0.125&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&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%; white-space: nowrap;" 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%; 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;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&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;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; white-space: nowrap;" valign="bottom"&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; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;6.6&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/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 table summarizes information about the equity and liability components of our outstanding &lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;0.125%&lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; Notes (in millions). We measured the fair values of the convertible notes outstanding based on quoted market prices, which is a Level 2 measurement at December 31, &lt;/span&gt;2020&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; and &lt;/span&gt;2019&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;table cellpadding="0" cellspacing="0" id="z9adf776942de41cfa98e122ffee7ca9c" 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;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/&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; text-indent: 16pt;"&gt;2020&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2019&lt;/div&gt;&lt;/td&gt;
    &lt;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;Fair value of outstanding 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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;564.9&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;558.7&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;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;Principal amount of convertible notes outstanding&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;548.8&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;548.8&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;&#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;Unamortized portion of debt discount&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;86.0&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;105.2&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 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 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;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;455.7&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;434.7&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: 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;Carrying value of equity component&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;105.8&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;105.8&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/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-style: italic;"&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;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Additionally, i&lt;/span&gt;n conjunction with the December 2019 exchange, 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 style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;0.125%&lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; Notes&lt;/span&gt; by increasing the conversion price even further. &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;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. 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;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;0.125%&lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; Notes&lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;. &lt;/span&gt;We accounted for our call spread transactions using the Derivatives and Hedging &#x2013; Contracts in Entity&#x2019;s Own Equity accounting guidance contained in Topic 815. We determined that the call spread transactions meet the definition of a derivative, are indexed to our stock and meet the criteria to be classified in shareholders&#x2019; equity.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&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;Similar to our &lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;0.125%&lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; Notes&lt;/span&gt;&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;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;0.125%&lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; Notes&lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;. The note hedges will expire upon maturity of &lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;0.125%&lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; Notes&lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;, or December 2024. The note hedges and warrants are separate transactions and are not part of the terms of our &lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;0.125%&lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; Notes&lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;. The holders of the &lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;0.125%&lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; Notes&lt;/span&gt;&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;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We recorded the aggregate amount paid for the note hedges and the aggregate amount received for the warrants in additional paid-in capital in our consolidated balance sheet. &lt;/span&gt;We reassess our ability to continue to classify the note hedges and warrants in shareholders&#x2019; equity at each reporting period. &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We excluded shares under the note hedges from our calculation of diluted earnings per share as they were antidilutive. We will include the shares issuable under the 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;/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;1 Percent Convertible Senior Notes&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In November 2014, we completed a $500 million offering of convertible senior notes, which mature in 2021 and bear interest at 1 percent. We used a substantial portion of the net proceeds from the issuance of the 1% Notes to repurchase $140 million in principal of our &lt;span style="-sec-ix-hidden:Fact_5720e35e625f4851a419d661f07222c0"&gt;2&#xbe; percent&lt;/span&gt; convertible senior notes, or &lt;span style="-sec-ix-hidden:Fact_aab0fa84211849a9a9227eb0f2f81996"&gt;2&#xbe;%&lt;/span&gt;% Notes. In December 2016, we issued an additional $185.5 million of 1% Notes in exchange for the redemption of $61.1 million of our &lt;span style="-sec-ix-hidden:Fact_1a854ab02ffa46d48ab09b0a92e8e673"&gt;2&#xbe;%&lt;/span&gt;% Notes. In December 2019, we exchanged a portion of our 1% Notes for &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;0.125%&lt;/span&gt; Notes. As a result, the principal balance of 1% Notes was $309.9 million. Additionally, we recorded a $21.9 million non-cash loss on early retirement of debt, reflecting the early retirement of a significant portion of our 1% Notes in December 2019.&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: 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;At December 31, 2020, we had the following 1% Notes outstanding (amounts in millions except price per share data):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" id="z7c00b82b222848c08f211e04a12df732" 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; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/&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;1% 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; white-space: nowrap;" 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; 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;309.9&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: top; white-space: nowrap;" 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; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: top;" valign="bottom"&gt;&lt;div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;November 30, 2021&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; background-color: #CCEEFF; white-space: nowrap;" 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; background-color: #CCEEFF; white-space: nowrap;" 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;1 percent&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 88%; white-space: nowrap;" 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%; 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;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&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;66.81&lt;/div&gt;&lt;/td&gt;
    &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; white-space: nowrap;" valign="bottom"&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; 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;4.6&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/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;Interest is payable semi-annually in arrears on May 15 and November 15 of each year for the 1% Notes. The 1% Notes are convertible at the option of the note holders prior to July 1, 2021 only under certain conditions. On or after July 1, 2021, the 1% Notes are initially convertible into approximately 4.6 million shares of common stock at a conversion price of approximately $66.81 per share. We will 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 1% Notes prior to maturity, and no sinking fund is provided for them. If we undergo a fundamental change, holders may require us to purchase for cash all or any portion of their 1% Notes at a purchase price equal to 100 percent of the principal amount of the notes to be purchased, plus accrued and unpaid interest to, but excluding, the fundamental change purchase date.&lt;/div&gt;

&lt;div style="display:none;"&gt;&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;The following table summarizes information about the equity and liability components of our outstanding &lt;/span&gt;1%&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; Notes (in millions). We measured the fair values of the convertible notes outstanding based on quoted market prices, which is a Level 2 measurement at December 31, &lt;/span&gt;2020&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; and &lt;/span&gt;2019&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;table cellpadding="0" cellspacing="0" id="z6aaac47fd8de480782bc6ae69dceb20c" 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;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/&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; text-indent: 16pt;"&gt;2020&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2019&lt;/div&gt;&lt;/td&gt;
    &lt;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;Fair value of outstanding 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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;338.5&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;354.8&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: 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;Principal amount of convertible notes outstanding&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;309.9&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;309.9&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;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;Unamortized portion of debt discount&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;15.8&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;32.8&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: 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;Current/long-term 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;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;293.2&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;275.3&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: 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;Carrying value of equity component&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;33.5&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;33.5&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;/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 account for our convertible notes using an accounting standard that requires us to assign a value to our convertible debt equal to the estimated fair value of similar debt instruments without the conversion feature and to record the remaining portion in equity. As a result, we recorded our convertible notes at a discount, which we are amortizing as additional non-cash interest expense over the expected life of the respective debt. We determined our nonconvertible debt borrowing rate using a combination of the present value of the debt&#x2019;s cash flows and a Black-Scholes valuation model. The following table summarizes the nonconvertible borrowing rate, effective interest rate and amortization period of our debt discount for our convertible notes:&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" id="z2fe2c231c3944d6a8692011908bb0bdd" 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: 39.54%; vertical-align: bottom;"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"/&gt;&lt;/td&gt;
    &lt;td style="width: 2.25%; vertical-align: bottom;"&gt;&#160;&lt;/td&gt;
    &lt;td style="width: 28.82%; vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;1% Notes&lt;/div&gt;&lt;/td&gt;
    &lt;td style="width: 1.39%; vertical-align: top;"&gt;&#160;&lt;/td&gt;
    &lt;td style="width: 28%; vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="text-align: center; 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;0.125%&lt;/span&gt; Notes&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="width: 39.54%; vertical-align: bottom; background-color: #CCEEFF;"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Nonconvertible debt borrowing rate&lt;/div&gt;&lt;/td&gt;
    &lt;td style="width: 2.25%; vertical-align: bottom; background-color: #CCEEFF;"&gt;&#160;&lt;/td&gt;
    &lt;td style="width: 28.82%; vertical-align: bottom; background-color: #CCEEFF;"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;7.4 percent&lt;/div&gt;&lt;/td&gt;
    &lt;td style="width: 1.39%; vertical-align: top; background-color: #CCEEFF;"&gt;&#160;&lt;/td&gt;
    &lt;td style="width: 28%; vertical-align: bottom; background-color: #CCEEFF;"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;4.4 percent&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="width: 39.54%; vertical-align: bottom; background-color: #FFFFFF;"&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 interest rate (1)&lt;/div&gt;&lt;/td&gt;
    &lt;td style="width: 2.25%; vertical-align: bottom; background-color: #FFFFFF;"&gt;&#160;&lt;/td&gt;
    &lt;td style="width: 28.82%; vertical-align: bottom; background-color: #FFFFFF;"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;7.5 percent&lt;/div&gt;&lt;/td&gt;
    &lt;td style="width: 1.39%; vertical-align: top; background-color: #FFFFFF;"&gt;&#160;&lt;/td&gt;
    &lt;td style="width: 28%; vertical-align: bottom; background-color: #FFFFFF;"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;4.9 percent&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="width: 39.54%; vertical-align: bottom; background-color: #CCEEFF;"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Amortization period of debt discount&lt;/div&gt;&lt;/td&gt;
    &lt;td style="width: 2.25%; vertical-align: bottom; background-color: #CCEEFF;"&gt;&#160;&lt;/td&gt;
    &lt;td style="width: 28.82%; vertical-align: bottom; background-color: #CCEEFF;"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;7 years&lt;/div&gt;&lt;/td&gt;
    &lt;td style="width: 1.39%; vertical-align: top; background-color: #CCEEFF;"&gt;&#160;&lt;/td&gt;
    &lt;td style="width: 28%; 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 years&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" id="zfe3e4e94d24b42be98cc86e80ead96fa" 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; vertical-align: top; align: right; 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;For our 1% Notes, our effective interest rate represents our effective interest rate after our December 2019 debt exchange.&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 total interest expense for our outstanding senior convertible notes for the years ended December 31, 2020, 2019 and 2018 included $38.7 million, $39.3 million and $35.2 million, respectively, of non-cash interest expense related to the amortization of the debt discount and 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; font-weight: bold;"&gt;Line of Credit 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;In June 2015, we entered into a five-year revolving line of credit agreement with Morgan Stanley Private Bank, National Association, or Morgan Stanley, which we amended in February 2016. Under the amended credit agreement, Morgan Stanley provided a maximum of $30 million of revolving credit for general working capital purposes. During the third quarter of 2019, we paid off our total outstanding borrowings of $12.5 million under the agreement and subsequently terminated 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; font-style: italic; font-weight: bold;"&gt;Research and Development and Manufacturing Facilities&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In July 2017, we purchased the building that houses our primary R&amp;amp;D facility for $79.4 million and our manufacturing facility for $14.0 million. We financed the purchase of these two facilities with mortgage debt of $60.4 million in total. Our primary R&amp;amp;D facility mortgage has 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 are only required to make interest payments. Both mortgages mature in August 2027.&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;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 debt and other obligation maturities, including fixed and determinable interest, at December 31, 2020 are as follows (in thousands):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" id="z4c8baa70053148028f3836d3d205e2fe" 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;2021&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;329,189&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #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;2022&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;3,495&lt;/div&gt;&lt;/td&gt;
    &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;2023&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;4,180&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #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;2024&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;553,006&lt;/div&gt;&lt;/td&gt;
    &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;2025&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;3,494&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #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;60,933&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;Subtotal&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;954,297&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;/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&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(300,462&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&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;(21,758&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&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%;" valign="bottom"&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: unamortized portion of debt discount&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(101,820&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&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: debt issuance costs&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(8,455&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&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;Plus: lease liabilities&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;17,310&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%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total long-term debt&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;539,112&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Operating Leases&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Carlsbad Leases&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We lease a facility adjacent to our manufacturing facility that has laboratory and office space that we use to support our manufacturing facility. We lease this space under a non-cancelable operating lease. In May 2020, we exercised our option to extend our lease, extending our lease term from June 2021 to August 2026. We have one remaining option to extend the lease for an additional five-year period.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We also lease additional office spaces in Carlsbad. We lease these spaces under non-cancelable operating leases with initial terms ending in 2023 with options to extend each of the leases for one&#160;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; font-style: italic;"&gt;Boston 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;We entered into an operating lease agreement for office space located in Boston, Massachusetts in the second quarter of 2018. The lease commencement date was in August 2018 and we took occupancy in September 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, which commenced on August 15, 2018, and a tenant improvement allowance up to $3.8 million. We provided the lessor with a letter of credit to secure its obligations under the lease in the initial amount of $2.4 million, to be reduced to $1.8 million on the third anniversary of the rent commencement date and to $1.2 million on the fifth anniversary of the rent commencement date if we meet certain conditions set forth in the lease at each such time.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&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.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&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" id="z0a8a9123d7d24adcb53d3ae530505e1b" 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;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/&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;At December 31, 2020&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 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 (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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;13.1&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 88%;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Operating lease liabilities (2)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;17.3&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: 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;7.2 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;7.0&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: 10pt;"&gt;________________&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z73aea46a179a456ab91ef0c8e323ab62" 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; vertical-align: top; align: right; 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 &lt;span style="-sec-ix-hidden:Fact_f81ca57385a04657b8ecd0f06d505159"&gt;deposits and other assets&lt;/span&gt; on our consolidated balance sheet.&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" id="zd0fe2a08d108427ab40244fed97b9a07" 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; vertical-align: top; align: right; 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;Current portion of $2.0 million was included in &lt;span style="-sec-ix-hidden:Fact_530181678e9244af8b37885d3ba85980"&gt;current portion of long-term obligations&lt;/span&gt; on our consolidated balance sheet, with the difference included in &lt;span style="-sec-ix-hidden:Fact_9c37cb3853f74a4f821bbe4ed37a06ba"&gt;long-term obligations&lt;/span&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, 2020, 2019, and 2018 we paid $3.8 million, $3.9 million and $1.7 million of lease payments, which were included in operating activities in our consolidated statement 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, 2020, 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" id="z04402bd2033b49df92fb5d8cb974b10a" 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;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Operating&lt;/span&gt; &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Leases&lt;/span&gt;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; 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;Year ending December 31,&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;$&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: 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;2021&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;3,193&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/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;2022&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2,968&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #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;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;2,707&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;/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;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2,583&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #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;2025&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2,442&lt;/div&gt;&lt;/td&gt;
    &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%; 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;Thereafter&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;7,038&lt;/div&gt;&lt;/td&gt;
    &lt;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: 88%;" 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%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;20,931&lt;/div&gt;&lt;/td&gt;
    &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: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;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;&#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: 88%; padding-bottom: 2px;" valign="bottom"&gt;&lt;div style="text-align: left; margin-left: 18.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Imputed interest&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;(3,621&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: left; margin-left: 36.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total operating lease 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;17,310&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;"&gt;Rent expense was $3.7 million, $3.6 million and $2.6 million for the years ended December 31, 2020, 2019 and 2018, respectively. &lt;/div&gt;
</us-gaap:DebtAndCapitalLeasesDisclosuresTextBlock>
    <us-gaap:ScheduleOfDebtInstrumentsTextBlock
      contextRef="c20200101to20201231"
      id="Text_487975f5bd5542cbb02179bbd1a60f54">
&lt;div style="display:none;"&gt;&lt;br/&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" id="z491d0b86fdec4ab1bf93c193d82169f5" 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;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/&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;2020&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2019&lt;/div&gt;&lt;/td&gt;
    &lt;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;0.125 percent 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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;455,719&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;434,711&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #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;1 percent convertible senior notes (1)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;293,161&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: 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;275,333&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Long-term mortgage debt&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;59,984&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;59,913&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;/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;Leases and other obligations&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;30,710&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;17,569&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%; 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&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;839,574&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;787,526&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; 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;Less: current portion (1)&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;(300,462&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;&lt;div style="font-family: 'Times 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;(2,026&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: 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; background-color: #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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;539,112&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;785,500&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" id="za3bbe36629904c01b690cbe109c76d9b" 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; vertical-align: top; align: right; 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;We classified the carrying value of our 1% Notes as a current liability on our consolidated balance sheet at December 31, 2020 because it matures in November 2021.&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;
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      contextRef="c20201231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember"
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    <us-gaap:DebtInstrumentInterestRateStatedPercentage
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      id="Text_599676c995b8459d807f45a7ee7d2f44">
&lt;div style="display:none;"&gt;&lt;br/&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, 2020, we had the following &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;0.125%&lt;/span&gt; Notes outstanding (amounts in millions except price per share data):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" id="zd6b190b45e7940aebc9709e23b39ca57" 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; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/&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;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;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; white-space: nowrap;" 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; 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;548.8&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; white-space: nowrap;" 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; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: top;" valign="bottom"&gt;&lt;div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;December 15, 2024&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 88%; background-color: #CCEEFF; white-space: nowrap;" 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%; 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;0.125&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&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%; white-space: nowrap;" 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%; 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;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&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;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; white-space: nowrap;" valign="bottom"&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; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;6.6&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/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 table summarizes information about the equity and liability components of our outstanding &lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;0.125%&lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; Notes (in millions). We measured the fair values of the convertible notes outstanding based on quoted market prices, which is a Level 2 measurement at December 31, &lt;/span&gt;2020&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; and &lt;/span&gt;2019&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;table cellpadding="0" cellspacing="0" id="z9adf776942de41cfa98e122ffee7ca9c" 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;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/&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; text-indent: 16pt;"&gt;2020&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2019&lt;/div&gt;&lt;/td&gt;
    &lt;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;Fair value of outstanding 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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;564.9&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;558.7&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;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;Principal amount of convertible notes outstanding&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;548.8&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;548.8&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;&#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;Unamortized portion of debt discount&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;86.0&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;105.2&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 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 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;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;455.7&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;434.7&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: 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;Carrying value of equity component&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;105.8&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;105.8&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/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: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;At December 31, 2020, we had the following 1% Notes outstanding (amounts in millions except price per share data):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" id="z7c00b82b222848c08f211e04a12df732" 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; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/&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;1% 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; white-space: nowrap;" 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; 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;309.9&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: top; white-space: nowrap;" 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; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: top;" valign="bottom"&gt;&lt;div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;November 30, 2021&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; background-color: #CCEEFF; white-space: nowrap;" 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; background-color: #CCEEFF; white-space: nowrap;" 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;1 percent&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 88%; white-space: nowrap;" 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%; 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;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&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;66.81&lt;/div&gt;&lt;/td&gt;
    &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; white-space: nowrap;" valign="bottom"&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; 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;4.6&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/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;The following table summarizes information about the equity and liability components of our outstanding &lt;/span&gt;1%&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; Notes (in millions). We measured the fair values of the convertible notes outstanding based on quoted market prices, which is a Level 2 measurement at December 31, &lt;/span&gt;2020&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; and &lt;/span&gt;2019&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;table cellpadding="0" cellspacing="0" id="z6aaac47fd8de480782bc6ae69dceb20c" 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;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/&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; text-indent: 16pt;"&gt;2020&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2019&lt;/div&gt;&lt;/td&gt;
    &lt;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;Fair value of outstanding 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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;338.5&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;354.8&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: 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;Principal amount of convertible notes outstanding&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;309.9&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;309.9&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;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;Unamortized portion of debt discount&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;15.8&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;32.8&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: 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;Current/long-term 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;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;293.2&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;275.3&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: 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;Carrying value of equity component&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;33.5&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;33.5&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;/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 account for our convertible notes using an accounting standard that requires us to assign a value to our convertible debt equal to the estimated fair value of similar debt instruments without the conversion feature and to record the remaining portion in equity. As a result, we recorded our convertible notes at a discount, which we are amortizing as additional non-cash interest expense over the expected life of the respective debt. We determined our nonconvertible debt borrowing rate using a combination of the present value of the debt&#x2019;s cash flows and a Black-Scholes valuation model. The following table summarizes the nonconvertible borrowing rate, effective interest rate and amortization period of our debt discount for our convertible notes:&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" id="z2fe2c231c3944d6a8692011908bb0bdd" 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: 39.54%; vertical-align: bottom;"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"/&gt;&lt;/td&gt;
    &lt;td style="width: 2.25%; vertical-align: bottom;"&gt;&#160;&lt;/td&gt;
    &lt;td style="width: 28.82%; vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;1% Notes&lt;/div&gt;&lt;/td&gt;
    &lt;td style="width: 1.39%; vertical-align: top;"&gt;&#160;&lt;/td&gt;
    &lt;td style="width: 28%; vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;&lt;div style="text-align: center; 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;0.125%&lt;/span&gt; Notes&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
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    &lt;td style="width: 28%; vertical-align: bottom; background-color: #CCEEFF;"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;4.4 percent&lt;/div&gt;&lt;/td&gt;
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    &lt;td style="width: 2.25%; vertical-align: bottom; background-color: #FFFFFF;"&gt;&#160;&lt;/td&gt;
    &lt;td style="width: 28.82%; vertical-align: bottom; background-color: #FFFFFF;"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;7.5 percent&lt;/div&gt;&lt;/td&gt;
    &lt;td style="width: 1.39%; vertical-align: top; background-color: #FFFFFF;"&gt;&#160;&lt;/td&gt;
    &lt;td style="width: 28%; vertical-align: bottom; background-color: #FFFFFF;"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;4.9 percent&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
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    &lt;td style="width: 2.25%; vertical-align: bottom; background-color: #CCEEFF;"&gt;&#160;&lt;/td&gt;
    &lt;td style="width: 28.82%; vertical-align: bottom; background-color: #CCEEFF;"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;7 years&lt;/div&gt;&lt;/td&gt;
    &lt;td style="width: 1.39%; vertical-align: top; background-color: #CCEEFF;"&gt;&#160;&lt;/td&gt;
    &lt;td style="width: 28%; 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 years&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" id="zfe3e4e94d24b42be98cc86e80ead96fa" 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; vertical-align: top; align: right; 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;For our 1% Notes, our effective interest rate represents our effective interest rate after our December 2019 debt exchange.&lt;/div&gt;&lt;/td&gt;
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    <us-gaap:DebtInstrumentCarryingAmount
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      decimals="-5"
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      contextRef="c20201231_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember"
      decimals="-5"
      id="Fact_692ce55b49e842f39e92b6574d933927"
      unitRef="U001">15800000</us-gaap:DebtInstrumentUnamortizedDiscountPremiumNet>
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      contextRef="c20191231_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember"
      decimals="-5"
      id="Fact_927ea0104b9648739f8cadf26fe8c648"
      unitRef="U001">32800000</us-gaap:DebtInstrumentUnamortizedDiscountPremiumNet>
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      contextRef="c20201231_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember"
      decimals="-5"
      id="Fact_4eefe8c5ad4f45dab9f8431005a68c88"
      unitRef="U001">293200000</us-gaap:ConvertibleDebtCurrent>
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      contextRef="c20191231_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember"
      decimals="-5"
      id="Fact_394e50c3174b419995a848e3ad315d86"
      unitRef="U001">275300000</us-gaap:ConvertibleDebtNoncurrent>
    <us-gaap:DebtInstrumentConvertibleCarryingAmountOfTheEquityComponent
      contextRef="c20201231_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember"
      decimals="-5"
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      unitRef="U001">33500000</us-gaap:DebtInstrumentConvertibleCarryingAmountOfTheEquityComponent>
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      contextRef="c20191231_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember"
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      id="Fact_275ed98d8a534881b164a506f08888da"
      unitRef="U001">33500000</us-gaap:DebtInstrumentConvertibleCarryingAmountOfTheEquityComponent>
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      decimals="2"
      id="Fact_54d20492d3454961ab50976a25101d84"
      unitRef="U003">0.01</us-gaap:DebtInstrumentInterestRateStatedPercentage>
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      contextRef="c20201231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember"
      decimals="5"
      id="Fact_4b335b7942d14e2abc8562afa2e5f0ec"
      unitRef="U003">0.00125</us-gaap:DebtInstrumentInterestRateStatedPercentage>
    <us-gaap:DebtInstrumentMeasurementInput
      contextRef="c20201231_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember_MeasurementInputTypeAxis_MeasurementInputDiscountRateMember"
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      id="Fact_ad2c1bc1c1f846a1affa31c79be4b69c"
      unitRef="U003">0.074</us-gaap:DebtInstrumentMeasurementInput>
    <us-gaap:DebtInstrumentMeasurementInput
      contextRef="c20201231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember_MeasurementInputTypeAxis_MeasurementInputDiscountRateMember"
      decimals="3"
      id="Fact_596bdc839a504047b97a479e25a26ff8"
      unitRef="U003">0.044</us-gaap:DebtInstrumentMeasurementInput>
    <us-gaap:DebtInstrumentInterestRateEffectivePercentage
      contextRef="c20201231_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember"
      decimals="3"
      id="Fact_04d37423456f431eae8b542d5d3b0213"
      unitRef="U003">0.075</us-gaap:DebtInstrumentInterestRateEffectivePercentage>
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      contextRef="c20201231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember"
      decimals="3"
      id="Fact_6ac68bb7b1894b778d0cc3db62132135"
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      contextRef="c20200101to20201231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember"
      id="Fact_0958d84136bc4152acbe44cfeef2d965">P5Y</us-gaap:DebtInstrumentConvertibleRemainingDiscountAmortizationPeriod1>
    <us-gaap:DebtInstrumentInterestRateStatedPercentage
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      decimals="2"
      id="Fact_e30378472c6741629087ed2375181d83"
      unitRef="U003">0.01</us-gaap:DebtInstrumentInterestRateStatedPercentage>
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      contextRef="c20200101to20201231"
      decimals="-5"
      id="Fact_9c53099ee180469b94aa9696977d2880"
      unitRef="U001">38700000</us-gaap:AmortizationOfFinancingCostsAndDiscounts>
    <us-gaap:AmortizationOfFinancingCostsAndDiscounts
      contextRef="c20190101to20191231"
      decimals="-5"
      id="Fact_bdbef3ccc85649118ae89b354a641e27"
      unitRef="U001">39300000</us-gaap:AmortizationOfFinancingCostsAndDiscounts>
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      contextRef="c20180101to20181231"
      decimals="-5"
      id="Fact_08ed41e893e1431f80a65f44ee96fab5"
      unitRef="U001">35200000</us-gaap:AmortizationOfFinancingCostsAndDiscounts>
    <us-gaap:DebtInstrumentTerm
      contextRef="c20200101to20201231_CreditFacilityAxis_RevolvingCreditFacilityMember_LineOfCreditFacilityAxis_MorganStanleyPrivateBankNationalAssociationMember"
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    <us-gaap:LineOfCreditFacilityMaximumBorrowingCapacity
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    <us-gaap:RepaymentsOfLongTermLinesOfCredit
      contextRef="c20190701to20190930_DebtInstrumentAxis_FixedRateNoteWithMorganStanleyMember"
      decimals="-5"
      id="Fact_df1b80118efc4ee18a12e9720dbc121d"
      unitRef="U001">12500000</us-gaap:RepaymentsOfLongTermLinesOfCredit>
    <us-gaap:PaymentsToAcquireBuildings
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      decimals="-5"
      id="Fact_4a0c024b965c4f51b897f9cf5bc80424"
      unitRef="U001">79400000</us-gaap:PaymentsToAcquireBuildings>
    <us-gaap:PaymentsToAcquireBuildings
      contextRef="c20170701to20170731_PropertyPlantAndEquipmentByTypeAxis_ManufacturingFacilityMember"
      decimals="-5"
      id="Fact_06974c574f644e5baacbd3f8e2c599a6"
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    <ions:NumberOfPurchasedFacilitiesFinancedWithMortgageDebt
      contextRef="c20150701to20150731"
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      id="Fact_802514d6121f4f3ca8efa9133eb869cd"
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    <us-gaap:DebtInstrumentFaceAmount
      contextRef="c20170731_DebtInstrumentAxis_LongTermMortgageDebtMember"
      decimals="-5"
      id="Fact_1c1b0d341f0d4a39b8dd7164eab2e39d"
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      decimals="4"
      id="Fact_2e21e0a6347e447a8991607c0227050a"
      unitRef="U003">0.0388</us-gaap:DebtInstrumentInterestRateStatedPercentage>
    <us-gaap:DebtInstrumentInterestRateStatedPercentage
      contextRef="c20170731_PropertyPlantAndEquipmentByTypeAxis_ManufacturingFacilityMember"
      decimals="4"
      id="Fact_b8df62c274f14f0499a84c79aa3dd4f9"
      unitRef="U003">0.0420</us-gaap:DebtInstrumentInterestRateStatedPercentage>
    <ions:PeriodToMakeInterestOnlyPaymentsOnMortgageLoan
      contextRef="c20200101to20201231_PropertyPlantAndEquipmentByTypeAxis_ManufacturingFacilityMember"
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    <ions:PeriodToMakeInterestOnlyPaymentsOnMortgageLoan
      contextRef="c20200101to20201231_PropertyPlantAndEquipmentByTypeAxis_PrimaryResearchAndDevelopmentFacilityMember"
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&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Annual debt and other obligation maturities, including fixed and determinable interest, at December 31, 2020 are as follows (in thousands):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" id="z4c8baa70053148028f3836d3d205e2fe" 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;2021&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;329,189&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #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;2022&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;3,495&lt;/div&gt;&lt;/td&gt;
    &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;2023&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;4,180&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #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;2024&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;553,006&lt;/div&gt;&lt;/td&gt;
    &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;2025&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;3,494&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #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;60,933&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;Subtotal&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;954,297&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;/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&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(300,462&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&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;(21,758&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&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%;" valign="bottom"&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: unamortized portion of debt discount&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(101,820&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&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: debt issuance costs&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(8,455&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&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;Plus: lease liabilities&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;17,310&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%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total long-term debt&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
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    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
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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;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" id="z0a8a9123d7d24adcb53d3ae530505e1b" 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;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/&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;At December 31, 2020&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 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 (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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;13.1&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
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    &lt;td style="vertical-align: bottom; width: 88%;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Operating lease liabilities (2)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;17.3&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: 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;7.2 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;
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    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;7.0&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: 10pt;"&gt;________________&lt;/div&gt;

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  &lt;tr&gt;
    &lt;td style="width: 36pt; vertical-align: top; align: right; 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 &lt;span style="-sec-ix-hidden:Fact_f81ca57385a04657b8ecd0f06d505159"&gt;deposits and other assets&lt;/span&gt; on our consolidated balance sheet.&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" id="zd0fe2a08d108427ab40244fed97b9a07" 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; vertical-align: top; align: right; 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;Current portion of $2.0 million was included in &lt;span style="-sec-ix-hidden:Fact_530181678e9244af8b37885d3ba85980"&gt;current portion of long-term obligations&lt;/span&gt; on our consolidated balance sheet, with the difference included in &lt;span style="-sec-ix-hidden:Fact_9c37cb3853f74a4f821bbe4ed37a06ba"&gt;long-term obligations&lt;/span&gt;.&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;
</ions:LesseeOperatingLeaseInformationTableTextBlock>
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      unitRef="U001">17300000</us-gaap:OperatingLeaseLiability>
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      id="Fact_ccfd1bbd8568445fb43b6a1d85973cc7">P7Y2M12D</us-gaap:OperatingLeaseWeightedAverageRemainingLeaseTerm1>
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      unitRef="U003">0.070</us-gaap:OperatingLeaseWeightedAverageDiscountRatePercent>
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      decimals="-5"
      id="Fact_9b0c762d64a740078d7920512d9fd9e9"
      unitRef="U001">2000000.0</us-gaap:OperatingLeaseLiabilityCurrent>
    <us-gaap:OperatingLeasePayments
      contextRef="c20200101to20201231"
      decimals="-5"
      id="Fact_826cead5743b4e90a9d8b807e97fe422"
      unitRef="U001">3800000</us-gaap:OperatingLeasePayments>
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      contextRef="c20190101to20191231"
      decimals="-5"
      id="Fact_297fcce7f2e44b348fe63e7be360cf7c"
      unitRef="U001">3900000</us-gaap:OperatingLeasePayments>
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      contextRef="c20180101to20181231"
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      unitRef="U001">1700000</us-gaap:OperatingLeasePayments>
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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;As of December 31, 2020, 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" id="z04402bd2033b49df92fb5d8cb974b10a" 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;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Operating&lt;/span&gt; &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Leases&lt;/span&gt;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; 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;Year ending December 31,&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;$&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: 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;2021&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;3,193&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/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;2022&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2,968&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #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;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;2,707&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;/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;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2,583&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #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;2025&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2,442&lt;/div&gt;&lt;/td&gt;
    &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%; 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;Thereafter&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;7,038&lt;/div&gt;&lt;/td&gt;
    &lt;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: 88%;" 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%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;20,931&lt;/div&gt;&lt;/td&gt;
    &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: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;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;&#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: 88%; padding-bottom: 2px;" valign="bottom"&gt;&lt;div style="text-align: left; margin-left: 18.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Imputed interest&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;(3,621&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: left; margin-left: 36.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total operating lease 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;17,310&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;
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&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;4. 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, 2020, 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, 2020.&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, 2020 and 2019, we had 300 million shares of common stock authorized, of which 140.4 million and 140.3 million were issued and outstanding, respectively. As of December 31, 2020, total common shares reserved for future issuance were 26.1 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, 2020, 2019 and 2018, we issued 1.7 million, 3.1 million and 1.5 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 $52.0 million, $119.7 million and $27.9 million in 2020, 2019 and 2018, respectively.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Share Repurchase Program&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In September 2019, our board of directors approved a share repurchase program of up to $125 million of our common stock. In 2019, we repurchased 535,000 shares for $34.4 million. In the first quarter of 2020, we repurchased an additional 1.5 million shares for $90.5 million.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Stock Plans&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;1989 Stock Option Plan&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In June 1989, our Board of Directors adopted, and the stockholders subsequently approved, a stock option plan that, as amended, provides for the issuance of non-qualified and incentive stock options for the purchase of up to 20.0 million shares of common stock to our employees, directors, and consultants. The plan expires in January 2024. The 1989 Plan does not allow us to grant stock bonuses or restricted stock awards and prohibits us from repricing any options outstanding under the plan unless our stockholders approve the repricing. Options vest over a four-year period, with 25percent exercisable at the end of one year from the date of the grant and the balance vesting ratably, on a monthly basis, thereafter and have a term of seven years. At December 31, 2020, a total of 30 thousand options were outstanding, of which options to purchase 30 thousand shares were exercisable, and 50 thousand shares were available for future grant under the 1989 Plan.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: -18pt; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;2011 Equity Incentive Plan&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In March 2011, our Board of Directors adopted, and the stockholders subsequently approved, a stock option plan that provides for the issuance of stock options, stock appreciation rights, restricted stock awards, restricted stock unit awards, and performance cash awards to our employees, directors, and consultants. In June 2015, May 2017 and June 2019, after receiving approval from our stockholders, we amended our 2011 Equity Incentive Plan 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. 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 options and restricted stock unit awards to our employees, directors and consultants. 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, 2020, a total of 11.4 million options were outstanding, of which 6.7 million were exercisable, 2.2 million restricted stock unit awards were outstanding, and 4.3 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. The stock options and restricted stock unit awards we issued to Dr. Stanley T. Crooke in his former role as chief executive officer and certain stock options and restricted stock unit awards we issued to B. Lynne Parshall in her former role as chief operating officer will accelerate upon a change of control, as defined in the 2011 Plan. 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. If we terminate one of our executive officers or if an executive officer 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 executive officers&#x2019; 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 Acquisition in October 2020, we assumed the unallocated portion of the available share reserve under the Akcea 2015 Equity Incentive Plan. In December 2020, we amended and restated the Akcea 2015 equity plan, including renaming the plan as the Ionis Pharmaceuticals, Inc. 2020 Equity Incentive Plan, or 2020 Plan. The 2020 Plan provided for the issuance of up to &lt;/span&gt;2.6&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million shares of our Common Stock to our employees, directors and consultants who were employees of Akcea prior to the Akcea Acquisition.&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 options and restricted stock unit awards to our eligible employees, directors and consultants. We have granted stock options to our employees under the 2020 Plan which vest annually over a four-year period. At December 31, 2020, a total of 0.01 million options were outstanding, of which none were exercisable, and 2.6 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" id="z1d2b880620554f7a8d859c8ac182b8a5" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; 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" id="z5ac0a33cd456453795b7a6dee28dcaac" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; 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" id="z0d47e7cb347a4be8aaf4f46a432dbcc2" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; 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" id="z52630d9833314cd2b584bf1e2514e71e" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; 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" id="z38a0cb52edc340b7a2694317e322760e" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; 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" id="z4573ab04cbdd482b87e9a572545982dc" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; 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 style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; &lt;/span&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: -18pt; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;2002 Non-Employee Directors&#x2019; Stock Option Plan&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In September 2001, our Board of Directors adopted, and the stockholders subsequently approved, an amendment and restatement of the 1992 Non-Employee Directors&#x2019; Stock Option Plan, which provides for the issuance of non-qualified stock options and restricted stock units to our non-employee directors. The name of the resulting plan is the 2002 Non-Employee Directors&#x2019; Stock Option Plan, or the 2002 Plan. In June 2015, after receiving approval from our stockholders, we amended our 2002 Plan to increase the total number of shares reserved for issuance from 1.2 million to 2.0 million. In June 2020, after receiving approval from our stockholders, we further amended our 2002 Plan. &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;The amendments included:&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z5e4f865f85114d45a89e7bb61564e0e0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; 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 &lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;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" id="z920b1672958340049e91b73e544ffb88" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; 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" id="z9dc5c7c10f39451a90ae42ff5d29e107" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; 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" id="z2ecc905910434dea959a202548f8b597" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; 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, 2020, a total of 1.0 million options were outstanding, of which 0.6 million were exercisable, 0.1 million restricted stock unit awards were outstanding, and 0.8 million shares were available for future grant under the 2002 Plan.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: -18pt; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Employee Stock Purchase Plan&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In June 2009, our Board of Directors adopted, and the stockholders subsequently approved, the amendment and restatement of the ESPP and we reserved an additional 150,000 shares of common stock for issuance thereunder. In each of the subsequent years until 2019, we reserved an additional 150,000 shares of common stock for the ESPP resulting in a total of 3.2 million shares authorized under the plan as of December 31, 2020. The ESPP permits full-time employees to purchase common stock through payroll deductions (which cannot exceed 10percent of each employee&#x2019;s compensation) at the lower of 85percent of fair market value at the beginning of the purchase period or the end of each purchase period. Under the amended and restated ESPP, employees must hold the stock they purchase for a minimum of six months from the date of purchase. During 2020, employees purchased and we issued to employees 0.06 million shares under the ESPP at a weighted average price of $43.65 per share. At December 31, 2020, there were 0.7 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, 2020 (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" id="zefbaea486274447a80de6c1c839baaef" 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;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/&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;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;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Weighted&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Average Exercise&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Price Per Share&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Average&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Remaining&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Contractual Term&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;(Years)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Aggregate&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Intrinsic&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Value&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Outstanding at December 31, 2019&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;11,001&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;51.48&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;2,764&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;59.89&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;(1,069&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;40.88&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;(361&lt;/div&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;56.48&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; 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;Outstanding at December 31, 2020&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;12,335&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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;54.14&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;4.16&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;55,885&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;Exercisable at December 31, 2020&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;7,366&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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;52.45&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;3.16&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;43,267&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 $29.43, $28.76 and $25.49 for the years ended December 31, 2020, 2019 and 2018, respectively. The total intrinsic value of options exercised during the years ended December 31, 2020, 2019 and 2018 were $15.5 million, $83.8 million and $34.8 million, respectively, which we determined as of the date of exercise. The amount of cash received from the exercise of stock options was $43.7 million, $105.9 million and $18.9 million for the years ended December 31, 2020, 2019 and 2018, respectively. For the year ended December 31, 2020, the weighted-average fair value of options exercised was $55.33. As of December 31, 2020, total unrecognized compensation cost related to non-vested stock options was $54.1 million. We expect to recognize this cost over a weighted average period of 1.1 years. We will adjust the total unrecognized compensation cost for future changes in estimated forfeitures.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Restricted Stock Unit Activity&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The following table summarizes the RSU activity for the year ended December 31, 2020 (in thousands, except per share data):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" id="zda6995a5dbd94d9990cbafed46af3aa1" 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;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/&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;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;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Weighted Average&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Grant Date Fair&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Value Per Share&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Non-vested at December 31, 2019&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,866&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;55.80&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 76%;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Granted&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,244&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;60.86&lt;/div&gt;&lt;/td&gt;
    &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;(602&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times 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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;53.68&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 76%; padding-bottom: 2px;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Cancelled/forfeited&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(134&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;58.96&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;Non-vested at December 31, 2020&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2,374&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;58.81&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, 2020, 2019 and 2018, the weighted-average grant date fair value of RSUs granted was $60.86, $60.23 and $51.06 per RSU, respectively. As of December 31, 2020, total unrecognized compensation cost related to RSUs was $55.3 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: 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, 2020, 2019 and 2018 (in thousands):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" id="zf582273af94a47d4a55e546cbe3c3f20" 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;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/&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;2020&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2019&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; 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;2018&lt;/div&gt;&lt;/td&gt;
    &lt;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 products sold&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,991&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;438&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;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;/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;115,584&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;95,348&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: 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;76,557&lt;/div&gt;&lt;/td&gt;
    &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;112,542&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #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;50,788&lt;/div&gt;&lt;/td&gt;
    &lt;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;54,595&lt;/div&gt;&lt;/td&gt;
    &lt;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;230,117&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;146,574&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;131,312&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;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Our non-cash stock-based compensation expense included &lt;/span&gt;$94.8 million, $37.1 million and $44.3 million &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;of stock-based compensation expense for Akcea employees for the years ended December 31, 2020, 2019 and 2018, respectively.&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In October 2020, as part of the Akcea Acquisition, Akcea&#x2019;s outstanding equity awards vested under Akcea&#x2019;s Plan. As a result, in the fourth quarter of 2020, we recognized all unrecognized stock-based compensation ($59.3 million) under Akcea&#x2019;s Plan. See Note 7, &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Akcea Acquisition&lt;/span&gt;, in the Notes to the Consolidated Financial Statements for further details.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&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 the third quarter of 2019, &lt;/span&gt;three&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; Akcea executive officers terminated their employment and entered into separation agreements with Akcea. As a result, in the third quarter of 2019, Akcea reversed $&lt;/span&gt;19.1&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million of stock-based compensation expense it had previously recognized related to the executive officers&#x2019; stock options and RSUs that were no longer going to vest.&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: -18pt; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Determining Fair Value&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&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;Valuation.&lt;/span&gt; We measure stock-based compensation expense for equity-classified awards, principally related to stock options, RSUs, and stock purchase rights under the ESPP at the grant date, based on the estimated fair value of the award and we recognize the expense over the employee&#x2019;s requisite service period. We value RSUs based on the market price of our common stock on the date of grant.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&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. The expected term of stock options granted represents the period of time that we expect them to be outstanding. We estimate the expected term of options granted based on actual and projected exercise patterns. We recognize compensation expense for stock options granted, RSUs, 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;"&gt;For the years ended December 31, 2020, 2019 and 2018, we used the following weighted-average assumptions in our Black-Scholes calculations:&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Ionis Employee Stock Options:&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" id="z5de1b8387f794ea89da0aaf36c178756" 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;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/&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;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;2020&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2019&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; 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;2018&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Risk-free interest rate&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1.5&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;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;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2.4&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: 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;58.6&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;60.3&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;63.0&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;4.7 years&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;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;4.8 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;4.6 years&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Ionis Board of Director Stock Options:&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" id="z5ed50e6f811d44c3a6aef8d3a577458a" 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;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/&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;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;2020&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2019&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; 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;2018&lt;/div&gt;&lt;/td&gt;
    &lt;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;0.5&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1.9&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;2.8&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 64%;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Dividend yield&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.0&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.0&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.0&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Volatility&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;57.6&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;60.7&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;61.5&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;" valign="bottom"&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;6.7 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;6.6 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;6.6 years&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Ionis ESPP:&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" id="z85916d3a965048b191b56294e70d2310" 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;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/&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;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;2020&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2019&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; 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;2018&lt;/div&gt;&lt;/td&gt;
    &lt;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;0.8&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2.4&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1.8&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 64%;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Dividend yield&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.0&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.0&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.0&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Volatility&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;47.9&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;45.6&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;47.3&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: 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. We estimated the expected term of options we have granted based on actual and projected 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;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&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 stock plans, Akcea had its own stock plan prior to the Akcea Acquisition, referred to as the Akcea 2015 Equity Incentive Plan, or Akcea Plan. Under the Akcea Plan, Akcea granted options and RSUs.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&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, 2020, 2019 and 2018, we used the following weighted-average assumptions in our Black-Scholes calculations for the Akcea 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; font-style: italic;"&gt;Akcea Employee Stock Options:&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" id="z27d73d5470a043818f1ac1d5b7d3bf8c" 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;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/&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;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;2020&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2019&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; 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;2018&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Risk-free interest rate&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1.1&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;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;2.8&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 64%;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Dividend yield&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.0&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.0&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.0&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Volatility&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;75.0&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;75.4&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;77.1&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;" valign="bottom"&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;6.08 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;6.09 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;6.08 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;Akcea Board of Director Stock Options:&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" id="z65411e08eef04f55b90f91e957d37dce" 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;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/&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;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;2020&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2019&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; 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;2018&lt;/div&gt;&lt;/td&gt;
    &lt;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;0.8&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1.8&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;/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;75.3&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;73.8&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;78.2&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;" valign="bottom"&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;5.67 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;6.25 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;6.42 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="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Akcea ESPP:&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" id="zcd9727188a3d4b1489d152685d6fe8c4" 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;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/&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;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;2020&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2019&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; 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;2018&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Risk-free interest rate&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1.0&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;2.4&lt;/div&gt;&lt;/td&gt;
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    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1.9&lt;/div&gt;&lt;/td&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;0.0&lt;/div&gt;&lt;/td&gt;
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    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
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    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-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;
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    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;60.0&lt;/div&gt;&lt;/td&gt;
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    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
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    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&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;" 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;
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&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;The following summarizes the Black-Scholes input methodology for Akcea options that differs from the methodology we use for Ionis 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;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Volatility.&lt;/span&gt; Since Akcea did not have sufficient history to estimate the volatility of its common stock, Akcea calculated its expected volatility based on a blend of its historical volatility and reported data from selected publicly traded peer companies for which historical information was available.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&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;Since Akcea did not have sufficient historical information, it used the simplified method for estimating its expected term. Under the simplified method Akcea calculated its expected term as the average time-to-vesting and the contractual life of the 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; font-style: italic;"&gt;Akcea 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 was based on the market price of Akcea&#x2019;s common stock on the date of grant. Akcea granted RSUs with various vesting terms between six months and four years. The weighted-average grant date fair value of RSUs granted to employees for years ended December 31, 2020 and 2019 was $15.57 and $21.95 per share, respectively.&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 the stock option activity under our stock plans for the year ended December 31, 2020 (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" id="zefbaea486274447a80de6c1c839baaef" 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;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/&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;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;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Weighted&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Average Exercise&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Price Per Share&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Average&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Remaining&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Contractual Term&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;(Years)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Aggregate&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Intrinsic&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Value&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Outstanding at December 31, 2019&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;11,001&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;51.48&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;2,764&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;59.89&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;(1,069&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;40.88&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;
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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="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;(361&lt;/div&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;56.48&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; 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;
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  &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;Outstanding at December 31, 2020&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;12,335&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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;54.14&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;4.16&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;55,885&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;Exercisable at December 31, 2020&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;7,366&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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;52.45&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;3.16&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;43,267&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, 2020 (in thousands, except per share data):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" id="zda6995a5dbd94d9990cbafed46af3aa1" 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;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/&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;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;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Weighted Average&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Grant Date Fair&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Value Per Share&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Non-vested at December 31, 2019&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,866&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;55.80&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 76%;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Granted&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,244&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;60.86&lt;/div&gt;&lt;/td&gt;
    &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;(602&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times 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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;53.68&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 76%; padding-bottom: 2px;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Cancelled/forfeited&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(134&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;58.96&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;Non-vested at December 31, 2020&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2,374&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;58.81&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 stock-based compensation expense for the years ended December 31, 2020, 2019 and 2018 (in thousands):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" id="zf582273af94a47d4a55e546cbe3c3f20" 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;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/&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;2020&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2019&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; 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;2018&lt;/div&gt;&lt;/td&gt;
    &lt;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 products sold&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,991&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;438&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;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;/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;115,584&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;95,348&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: 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;76,557&lt;/div&gt;&lt;/td&gt;
    &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;112,542&lt;/div&gt;&lt;/td&gt;
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    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #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;50,788&lt;/div&gt;&lt;/td&gt;
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    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
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    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;230,117&lt;/div&gt;&lt;/td&gt;
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    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;146,574&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;131,312&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;
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&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Ionis Employee Stock Options:&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

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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;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2018&lt;/div&gt;&lt;/td&gt;
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  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Risk-free interest rate&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1.5&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;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;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2.4&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;
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    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;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;58.6&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;60.3&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;63.0&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;
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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;" valign="bottom"&gt;&lt;div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;4.8 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;4.6 years&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Ionis Board of Director Stock Options:&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" id="z5ed50e6f811d44c3a6aef8d3a577458a" 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;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/&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;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;2020&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2019&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; 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;2018&lt;/div&gt;&lt;/td&gt;
    &lt;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;0.5&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1.9&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;2.8&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 64%;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Dividend yield&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.0&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.0&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.0&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Volatility&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;57.6&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;60.7&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;61.5&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;" valign="bottom"&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;6.7 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;6.6 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;6.6 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;Ionis ESPP:&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" id="z85916d3a965048b191b56294e70d2310" 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;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/&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;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;2020&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2019&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; 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;2018&lt;/div&gt;&lt;/td&gt;
    &lt;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;0.8&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2.4&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1.8&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 64%;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Dividend yield&lt;/div&gt;&lt;/td&gt;
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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;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;47.9&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;45.6&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;47.3&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;
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  &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;
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    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&lt;div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;6 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;
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&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Akcea Employee Stock Options:&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&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;December 31,&lt;/div&gt;&lt;/td&gt;
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    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
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    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
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    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-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;
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    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;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;2.8&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 64%;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Dividend yield&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.0&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.0&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.0&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Volatility&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;75.0&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;75.4&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;77.1&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;" valign="bottom"&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;6.08 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;6.09 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;6.08 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;Akcea Board of Director Stock Options:&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" id="z65411e08eef04f55b90f91e957d37dce" 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;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/&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;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;2020&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2019&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; 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;2018&lt;/div&gt;&lt;/td&gt;
    &lt;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;0.8&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1.8&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;/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;75.3&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;73.8&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;78.2&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;" valign="bottom"&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;5.67 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;6.25 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;6.42 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;Akcea ESPP:&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" id="zcd9727188a3d4b1489d152685d6fe8c4" 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;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/&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;December 31,&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
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  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2020&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2019&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; 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;2018&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
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    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
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    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2.4&lt;/div&gt;&lt;/td&gt;
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    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1.9&lt;/div&gt;&lt;/td&gt;
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  &lt;/tr&gt;
  &lt;tr&gt;
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    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;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;71.9&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;60.0&lt;/div&gt;&lt;/td&gt;
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    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;64.2&lt;/div&gt;&lt;/td&gt;
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    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
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&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;5. Income Taxes&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Income (loss) before income taxes is comprised of (in thousands):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" id="zdf6378ab0c1f4e95a0d1c6544909bef1" 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;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/&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;2020&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2019&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; 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;2018&lt;/div&gt;&lt;/td&gt;
    &lt;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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(172,702&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;344,280&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(69,576&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&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;2,670&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;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;2,489&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;(6,580&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 64%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Income (loss) before income taxes&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(170,032&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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;346,769&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;(76,156&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" id="zfa527624d6724c5ba0ce2f4dc24bcb29" 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;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/&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;2020&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2019&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; 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;2018&lt;/div&gt;&lt;/td&gt;
    &lt;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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(837&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-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;438&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #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;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;3,782&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;14,329&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(1,442&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&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;518&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #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;413&lt;/div&gt;&lt;/td&gt;
    &lt;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;374&lt;/div&gt;&lt;/td&gt;
    &lt;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;3,463&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;50,603&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: 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;(630&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&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;313,271&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(7,096&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times 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;(290,511&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&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;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;313,271&lt;/div&gt;&lt;/td&gt;
    &lt;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;(7,096&lt;/div&gt;&lt;/td&gt;
    &lt;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;(290,511&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 64%; 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;316,734&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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;43,507&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;(291,141&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: justify; 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 income (loss) before taxes. The sources and tax effects of the differences are as follows (in thousands):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" id="zcb2d6ab6c48e4c278e66d61bd2c81d98" 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;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/&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;2020&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;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;2019&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; 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;2018&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Pre-tax income (loss)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(170,032&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;346,769&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="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;(76,156&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;(35,707&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;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-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;72,822&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-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;(15,993&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times 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;(39,230&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times 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;23.1&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;49,119&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: 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;14.2&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;(2,202&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times 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;2.9&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;Foreign&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;49&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-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;340&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.1&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,735&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(2.3&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: 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;437,597&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;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(257.4&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;(37,765&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times 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;(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;&lt;div style="font-family: 'Times 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;(277,924&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times 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;364.9&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;Net operating loss expiration&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-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;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;&#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;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;8,864&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(11.6&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: 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;TEGSEDI licensing gain&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-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;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;&#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;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;59,583&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: 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;(78.2&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%; 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;Impact from outside basis differences&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-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;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;(16,344&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(4.7&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;&#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;0.0&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 28%;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;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;(18,774&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;11.0&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;(22,296&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times 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;(6.4&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;(73,362&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times 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;96.3&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; 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;(206&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.1&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;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;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.2&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;9,947&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(13.1&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;(29,131&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;17.1&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;1,811&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: 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;0.5&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;(1,808&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times 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;2.4&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 28%; 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;7,931&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(4.7&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;3,361&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1.0&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times 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;3,154&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(4.1&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;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;193&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(0.1&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" 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%; 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;(569&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times 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;0.7&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; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Stock-based compensation&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;17,435&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(10.3&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;(4,837&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(1.4&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(4,199&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times 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;5.5&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; 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%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-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;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;(2,071&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times 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;(0.6&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;&#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;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: 28%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Impacts from Akcea Acquisition&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(22,032&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times 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;13.0&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-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%; padding-bottom: 2px;" 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;" valign="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;(1,391&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;0.8&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(1,608&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;(0.5&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; 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;1,633&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;(2.1&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: 28%; 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;Effective rate&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;316,734&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(186.4&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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;43,507&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;12.6&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;(291,141&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;&#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;382.3&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="display:none;"&gt;&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, 2020 and 2019 are as follows (in thousands):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" id="zae724c9b7f994507b05f251f1d96b8e5" 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;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/&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;2020&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2019&lt;/div&gt;&lt;/td&gt;
    &lt;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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;83,681&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;20,191&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #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;245,746&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: 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;210,455&lt;/div&gt;&lt;/td&gt;
    &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;124,452&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;127,763&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #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;80,055&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;65,703&lt;/div&gt;&lt;/td&gt;
    &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;98,443&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;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;77,861&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;/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;13,402&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;12,510&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;645,779&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;514,483&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #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;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;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(2,920&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;(6,110&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&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;Fixed 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;(3,611&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times 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;(1,958&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
  &lt;/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;(5,808&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;(3,884&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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;633,440&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;502,531&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #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;(633,440&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;(196,974&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;305,557&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;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;Ionis and Akcea have filed separate U.S. federal income tax returns since Akcea&#x2019;s IPO in 2017. Accordingly, we were required to assess our Ionis stand-alone and Akcea&#x2019;s valuation allowances separately even though we consolidate Akcea&#x2019;s financial results in our consolidated financial statements. However, as a result of the Akcea acquisition, Ionis and Akcea will file a consolidated U.S. federal income tax return beginning in the fourth quarter of 2020, and we therefore assessed our U.S. federal valuation allowance requirements on a consolidated basis as of that period. We continue to assess the state portion of our valuation allowance on a consolidated basis.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&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 assessed our valuation allowance requirements and recorded a valuation allowance of $313 million against all of Ionis&#x2019; U.S. federal net deferred tax assets in the fourth quarter of 2020, due to uncertainties related to our ability to realize the tax benefits associated with these assets. This determination is based largely on Akcea rejoining the Ionis U.S. consolidated federal tax group in the fourth quarter of 2020. Due to Akcea&#x2019;s historical and projected financial statement losses, and the negative impact this is expected to have on Ionis&#x2019; consolidated taxable income, there is uncertainty of generating sufficient consolidated pre-tax income in future periods to realize the Ionis deferred tax benefits. It is also expected that Ionis&#x2019; pre-tax income in future periods may be lower due to increased research and development expenses associated with our pipeline of wholly owned medicines. We now maintain a valuation allowance against all our consolidated U.S. federal and state net 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 $436 million from December 31, 2019 to December 31, 2020. $313 million of the increase related to the valuation allowance established against our beginning of the year balance of Ionis&#x2019; U.S. federal net deferred tax assets as discussed above, which resulted in us recognizing income tax expense during 2020. The remaining increase in our valuation allowance related to current year changes in our net 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;At December 31, 2020, we had federal and state, primarily California, tax net operating loss carryforwards of $243.3 million and $346.3 million, respectively. Our federal tax loss carryforwards are available indefinitely. Our California tax loss carryforwards will begin to expire in 2031. At December 31, 2020, we also had federal and California research and development tax credit carryforwards of $210.5 million and $87.4 million, respectively. Our Federal research and development tax credit carryforwards will begin to expire in 2034. Our California research and development tax credit carryforwards are available indefinitely.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Utilization of the net operating loss and tax credit carryforwards may be subject to an annual limitation due to the ownership change limitations provided by the Internal Revenue Code of 1986, as amended, and similar state provisions. The annual limitation may result in the expiration of net operating losses and credits before utilization.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We analyze filing positions in all U.S. federal, state and foreign jurisdictions where we file income tax returns, and all open tax years in these jurisdictions to determine if we have any uncertain tax positions on any of our income tax returns. We recognize the impact of an uncertain tax position on an income tax return at the largest amount that the relevant taxing authority is more-likely-than not to sustain upon audit. We do not recognize uncertain income tax positions if they have less than 50 percent likelihood of the applicable tax authority sustaining our position.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The following table summarizes our gross unrecognized tax benefits (in thousands):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" id="z20fa178d8de346858dcbfb940644c973" 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;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/&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;2020&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2019&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; 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;2018&lt;/div&gt;&lt;/td&gt;
    &lt;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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;69,784&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;68,301&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;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;78,014&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: 64%;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Decrease for prior period tax positions&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(24,154&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(867&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times 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;(12,814&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Increase for prior period tax positions&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;7,023&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;736&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-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;Increase for current period tax positions&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,510&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;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;1,614&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;3,101&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 64%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Ending balance of unrecognized tax benefits&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;54,163&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;69,784&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;68,301&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Included in the balance of unrecognized tax benefits at December 31, 2020 and 2019 was $6.4 million and $0.4 million respectively, that if we recognized, could impact our effective tax rate, subject to our remaining valuation allowance. None of our unrecognized tax benefits recorded at December 31, 2018 would impact our effective tax rate, if we recognized them.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&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 foresee any material changes to our gross unrecognized tax benefits within the next twelve months.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&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 interest and/or penalties related to income tax matters in income tax expense. During the year ended December 31, &lt;/span&gt;2020&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;, we recognized $&lt;/span&gt;0.3&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million of accrued interest and penalties related to gross unrecognized tax benefits&lt;/span&gt;. We did not record any accrued interest and penalties for the years ended December 31, 2019 and 2018.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We are subject to taxation in the U.S. and various state and foreign jurisdictions. &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Our tax years for 1999 through 2019 are subject to examination by the U.S. federal, state and foreign tax authorities.&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 do not provide for a U.S. income tax liability and foreign withholding taxes on undistributed foreign earnings of our foreign subsidiaries as we consider those earnings to be permanently reinvested. It is not practicable for us to calculate the amount of unrecognized deferred tax liabilities associated with these earnings.&lt;/div&gt;
</us-gaap:IncomeTaxDisclosureTextBlock>
    <us-gaap:ScheduleOfIncomeBeforeIncomeTaxDomesticAndForeignTableTextBlock
      contextRef="c20200101to20201231"
      id="Text_7281bd0eb54443b994694c659a6a8f66">
&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Income (loss) before income taxes is comprised of (in thousands):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" id="zdf6378ab0c1f4e95a0d1c6544909bef1" 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;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/&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;2020&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2019&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; 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;2018&lt;/div&gt;&lt;/td&gt;
    &lt;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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(172,702&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;344,280&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(69,576&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&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;2,670&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;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;2,489&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;(6,580&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 64%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Income (loss) before income taxes&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(170,032&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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;346,769&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;(76,156&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="c20200101to20201231"
      decimals="-3"
      id="Fact_1154d9477ea5403c89bcaba61b591e79"
      unitRef="U001">-172702000</us-gaap:IncomeLossFromContinuingOperationsBeforeIncomeTaxesDomestic>
    <us-gaap:IncomeLossFromContinuingOperationsBeforeIncomeTaxesDomestic
      contextRef="c20190101to20191231"
      decimals="-3"
      id="Fact_74d3abad4f744e0aa68801acc3a6ed6b"
      unitRef="U001">344280000</us-gaap:IncomeLossFromContinuingOperationsBeforeIncomeTaxesDomestic>
    <us-gaap:IncomeLossFromContinuingOperationsBeforeIncomeTaxesDomestic
      contextRef="c20180101to20181231"
      decimals="-3"
      id="Fact_8977ca2c8272434794efd8259c5f22b7"
      unitRef="U001">-69576000</us-gaap:IncomeLossFromContinuingOperationsBeforeIncomeTaxesDomestic>
    <us-gaap:IncomeLossFromContinuingOperationsBeforeIncomeTaxesForeign
      contextRef="c20200101to20201231"
      decimals="-3"
      id="Fact_70ca994a31be49619caefe5e71de1587"
      unitRef="U001">2670000</us-gaap:IncomeLossFromContinuingOperationsBeforeIncomeTaxesForeign>
    <us-gaap:IncomeLossFromContinuingOperationsBeforeIncomeTaxesForeign
      contextRef="c20190101to20191231"
      decimals="-3"
      id="Fact_8425f2adaf6948cdb4db61cdf7def1fc"
      unitRef="U001">2489000</us-gaap:IncomeLossFromContinuingOperationsBeforeIncomeTaxesForeign>
    <us-gaap:IncomeLossFromContinuingOperationsBeforeIncomeTaxesForeign
      contextRef="c20180101to20181231"
      decimals="-3"
      id="Fact_15eeca6092a14a5c9b839eb716ea8ae4"
      unitRef="U001">-6580000</us-gaap:IncomeLossFromContinuingOperationsBeforeIncomeTaxesForeign>
    <us-gaap:IncomeLossFromContinuingOperationsBeforeIncomeTaxesMinorityInterestAndIncomeLossFromEquityMethodInvestments
      contextRef="c20200101to20201231"
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      id="Fact_317564d38d3f4684aaa47f65a5d386e8"
      unitRef="U001">-170032000</us-gaap:IncomeLossFromContinuingOperationsBeforeIncomeTaxesMinorityInterestAndIncomeLossFromEquityMethodInvestments>
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    <us-gaap:ScheduleOfComponentsOfIncomeTaxExpenseBenefitTableTextBlock
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&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Our 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" id="zfa527624d6724c5ba0ce2f4dc24bcb29" 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;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/&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;2020&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2019&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; 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;2018&lt;/div&gt;&lt;/td&gt;
    &lt;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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(837&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-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;438&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #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;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;3,782&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;14,329&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(1,442&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&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;518&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #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;413&lt;/div&gt;&lt;/td&gt;
    &lt;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;374&lt;/div&gt;&lt;/td&gt;
    &lt;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;3,463&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;50,603&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: 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;(630&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&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;313,271&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(7,096&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times 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;(290,511&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&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;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;313,271&lt;/div&gt;&lt;/td&gt;
    &lt;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;(7,096&lt;/div&gt;&lt;/td&gt;
    &lt;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;(290,511&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 64%; 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;316,734&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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;43,507&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;(291,141&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>
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      contextRef="c20190101to20191231"
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      id="Fact_18598915ff304ad69c4f603530fa17ba"
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      contextRef="c20180101to20181231"
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      id="Fact_b16b487bd08b4f16b0833b9f760c9124"
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      contextRef="c20200101to20201231"
      decimals="-3"
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      contextRef="c20190101to20191231"
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      id="Fact_7ac2061535c24653b193dc9c25179163"
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      contextRef="c20180101to20181231"
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&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Our expense (benefit) for income taxes differs from the amount computed by applying the U.S. federal statutory rate to income (loss) before taxes. The sources and tax effects of the differences are as follows (in thousands):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" id="zcb2d6ab6c48e4c278e66d61bd2c81d98" 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;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/&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;2020&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;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;2019&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; 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;2018&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Pre-tax income (loss)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(170,032&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;346,769&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="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;(76,156&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;(35,707&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;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-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;72,822&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-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;(15,993&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times 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;(39,230&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times 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;23.1&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;49,119&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: 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;14.2&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;(2,202&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times 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;2.9&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;Foreign&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;49&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-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;340&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.1&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,735&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(2.3&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: 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;437,597&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;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(257.4&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;(37,765&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times 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;(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;&lt;div style="font-family: 'Times 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;(277,924&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times 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;364.9&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;Net operating loss expiration&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-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;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;&#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;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;8,864&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(11.6&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: 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;TEGSEDI licensing gain&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-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;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;&#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;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;59,583&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: 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;(78.2&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%; 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;Impact from outside basis differences&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-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;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;(16,344&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(4.7&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;&#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;0.0&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 28%;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;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;(18,774&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;11.0&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;(22,296&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times 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;(6.4&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;(73,362&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times 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;96.3&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; 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;(206&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.1&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;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;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.2&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;9,947&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(13.1&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;(29,131&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;17.1&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;1,811&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: 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;0.5&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;(1,808&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times 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;2.4&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 28%; 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;7,931&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(4.7&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;3,361&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1.0&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times 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;3,154&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(4.1&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;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;193&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(0.1&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" 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%; 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;(569&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times 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;0.7&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; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Stock-based compensation&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;17,435&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(10.3&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;(4,837&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(1.4&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(4,199&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times 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;5.5&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; 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%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-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;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;(2,071&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times 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;(0.6&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;&#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;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: 28%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Impacts from Akcea Acquisition&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(22,032&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times 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;
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    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
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    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
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    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
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    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
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  &lt;tr&gt;
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    &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;
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    &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;0.8&lt;/div&gt;&lt;/td&gt;
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    &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;(1,608&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;
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    &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;(0.5&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)%&lt;/div&gt;&lt;/td&gt;
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    &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;1,633&lt;/div&gt;&lt;/td&gt;
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    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
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  &lt;tr&gt;
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    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
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    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(186.4&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;$&lt;/div&gt;&lt;/td&gt;
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    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;12.6&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
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    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
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    &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;382.3&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;
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      contextRef="c20190101to20191231"
      decimals="3"
      id="Fact_f0cc7188c05e4808b694a7a38a1291cc"
      unitRef="U003">0.126</us-gaap:EffectiveIncomeTaxRateContinuingOperations>
    <us-gaap:IncomeTaxExpenseBenefit
      contextRef="c20180101to20181231"
      decimals="-3"
      id="Fact_05f18d362e2441e2a636fa371d9e87f0"
      unitRef="U001">-291141000</us-gaap:IncomeTaxExpenseBenefit>
    <us-gaap:EffectiveIncomeTaxRateContinuingOperations
      contextRef="c20180101to20181231"
      decimals="3"
      id="Fact_b6d022290a824526a58ab495c81c8422"
      unitRef="U003">3.823</us-gaap:EffectiveIncomeTaxRateContinuingOperations>
    <us-gaap:ScheduleOfDeferredTaxAssetsAndLiabilitiesTableTextBlock
      contextRef="c20200101to20201231"
      id="Text_bc622eca11e84c0c8cebdfd099e985df">
&lt;div style="display:none;"&gt;&lt;br/&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, 2020 and 2019 are as follows (in thousands):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" id="zae724c9b7f994507b05f251f1d96b8e5" 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;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/&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;2020&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2019&lt;/div&gt;&lt;/td&gt;
    &lt;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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;83,681&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;20,191&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #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;245,746&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: 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;210,455&lt;/div&gt;&lt;/td&gt;
    &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;124,452&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;127,763&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #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;80,055&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;65,703&lt;/div&gt;&lt;/td&gt;
    &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;98,443&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;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;77,861&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;/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;13,402&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;12,510&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;645,779&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;514,483&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #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;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;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(2,920&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;(6,110&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&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;Fixed 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;(3,611&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times 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;(1,958&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
  &lt;/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;(5,808&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;(3,884&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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;633,440&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;502,531&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #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;(633,440&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;(196,974&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;305,557&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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      contextRef="c20191231"
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      contextRef="c20191231"
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      id="Fact_8fd4dba767ea4fb1ad2e077d22dd1144"
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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 (in thousands):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" id="z20fa178d8de346858dcbfb940644c973" 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;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/&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;2020&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2019&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; 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;2018&lt;/div&gt;&lt;/td&gt;
    &lt;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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;69,784&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;68,301&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;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;78,014&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;
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    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(24,154&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
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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;(867&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&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;(12,814&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&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;
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    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;7,023&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;736&lt;/div&gt;&lt;/td&gt;
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    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-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;
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  &lt;/tr&gt;
  &lt;tr&gt;
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    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,510&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;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;1,614&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;3,101&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 64%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Ending balance of unrecognized tax benefits&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;54,163&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;69,784&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;68,301&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;
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&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;6. 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="display:none;"&gt;&lt;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;Biogen&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We have several strategic collaborations with Biogen focused on using antisense technology to advance the treatment of neurological disorders. These collaborations combine our expertise in creating antisense medicines with Biogen&#x2019;s expertise in developing therapies for neurological disorders. We developed and licensed to Biogen SPINRAZA, our approved medicine to treat people with spinal muscular atrophy, or SMA. We and Biogen are currently developing eight investigational medicines to treat neurodegenerative diseases under these collaborations, including medicines in development to treat people with ALS, Alzheimer&#x2019;s disease&lt;sub&gt;&#160;&lt;/sub&gt;and Parkinson&#x2019;s disease. In addition to these medicines, our collaborations with Biogen include a substantial research pipeline that addresses a broad range of neurological diseases. From inception through December 2020, we have received more than $2.8 billion from our Biogen collaborations.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;"&gt;Spinal Muscular Atrophy Collaborations&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;SPINRAZA&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;In January 2012, we entered into a collaboration agreement with Biogen to develop and commercialize SPINRAZA, an RNA-targeted therapy for the treatment of SMA. &lt;/span&gt;SPINRAZA is approved in over 50 countries around the world. &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;From inception through December 2020, we earned more than $&lt;/span&gt;1.3&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;930&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million in revenue from SPINRAZA royalties and more than $&lt;/span&gt;435&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; font-style: italic;"&gt;New antisense medicines for the treatment of SMA&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;In December 2017, we entered into a collaboration agreement with Biogen to &lt;/span&gt;identify &lt;span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;new antisense medicines for the treatment of SMA&lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;. &lt;/span&gt;&lt;span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Biogen has the option to license therapies arising out of this collaboration following the completion of preclinical studies. Upon licensing, Biogen &lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;will be responsible for global development, regulatory and commercialization activities and costs for such therapies&lt;/span&gt;&lt;span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;. Under the collaboration agreement, we received a &lt;/span&gt;$25 million&lt;span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; upfront payment in the fourth quarter of 2017. We will receive development and regulatory milestone payments from Biogen if new medicines advance towards marketing approval. &lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;In total over the term of our collaboration, we are eligible to receive up to $&lt;/span&gt;1.2&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; billion in license fees, milestone payments and other payments, including up to $&lt;/span&gt;80&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million for the achievement of development milestones, up to $&lt;/span&gt;180&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million for the achievement of commercialization milestones and up to $&lt;/span&gt;800&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million for the achievement of sales milestones. In addition, we are eligible to receive tiered royalties &lt;/span&gt;&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;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;mid-&lt;/span&gt;20 percent&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; range &lt;/span&gt;&lt;span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;on net sales.&lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; We will achieve the next payment of up to $&lt;/span&gt;60&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million&lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;for the license of a medicine under this collaboration. &lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;At the commencement of this collaboration, we identified one performance obligation, which was to perform R&amp;amp;D services for Biogen. We determined the transaction price to be the $25 million upfront payment we received when we entered into the collaboration. We allocated the transaction price to our single performance obligation. In the fourth quarter of 2019, we completed our R&amp;amp;D services performance obligation under this collaboration. We recognized revenue as we performed services based on our effort to satisfy our performance obligation relative to the total effort expected to satisfy our performance obligation. We completed our performance obligation earlier than we previously estimated, as a result, we recognized $8.3 million of additional revenue in the fourth quarter of 2019. We do not have any remaining performance obligations under this collaboration. We will receive development and regulatory milestone payments from Biogen if Biogen advances the development candidate under this collaboration toward marketing 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; font-style: italic; font-weight: bold;"&gt;Neurology Collaborations&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;2018 Strategic Neurology&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;In April 2018, we and Biogen entered into a strategic collaboration to develop novel antisense medicines for a broad range of neurological diseases and entered into a SPA. As part of the collaboration, Biogen gained exclusive rights to the use of our antisense technology to develop therapies for these diseases for &lt;/span&gt;10&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; years. We are responsible for the identification of antisense drug candidates based on selected medicines&lt;/span&gt;. Biogen is responsible for conducting IND-enabling toxicology studies for the selected medicine. &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Biogen will have the option to license the selected medicine &lt;/span&gt;after it completes the IND-enabling toxicology study. &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;If Biogen exercises its option to license a medicine, it will assume global development, regulatory and commercialization responsibilities and costs for that medicine.&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;In the second quarter of 2018, 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;span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We 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 in milestone payments for each medicine that achieves marketing approval. &lt;/span&gt;In addition, we are eligible to receive tiered royalties &lt;span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;up to the &lt;/span&gt;20 percent range &lt;span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;on net sales.&lt;/span&gt;&#160;&lt;span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;W&lt;/span&gt;e are advancing eight programs under this collaboration and from inception through December 2020, we have received $1.05 billion in payments under this collaboration. We will achieve the next payment of $7.5 million if we advance a program&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;under this collaboration. &lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;At the commencement of this collaboration, &lt;/span&gt;we 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 2020, we have included $608 million &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;in payments in the transaction price for our R&amp;amp;D services performance obligation under this collaboration, including $&lt;/span&gt;11&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million of milestone payments we achieved in 2020 and $&lt;/span&gt;30&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million of milestone payments we achieved in 2019. These milestone payments did not create new performance obligations because they are part of our original R&amp;amp;D services performance obligation. Therefore, we included these amounts in our transaction price for our R&amp;amp;D services performance obligation in the period we achieved the milestone payment. We are recognizing revenue for our R&amp;amp;D services performance obligation as we perform services based on our effort to satisfy our performance obligation relative to our total effort expected to satisfy our performance obligation. We currently estimate we will satisfy our performance obligation at the end of the contractual term in June 2028.&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;2013 Strategic Neurology&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In September 2013, we and Biogen entered into a long-term strategic relationship focused on applying antisense technology to advance the treatment of neurodegenerative diseases. As part of the collaboration, Biogen gained exclusive rights to the use of our antisense technology to develop therapies for neurological diseases and has the option to license medicines resulting from this collaboration. We will usually be responsible for drug discovery and early development of antisense medicines and Biogen will have the option to license antisense medicines after Phase 2 proof-of-concept. In October 2016, we expanded our collaboration to include additional research activities we will perform. If Biogen exercises its option to license a medicine, it will assume global development, regulatory and commercialization responsibilities and costs for that medicine. We are currently advancing six 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), three medicines for ALS (tofersen, IONIS-C9&lt;sub&gt;Rx&lt;/sub&gt; and ION541), &lt;span style="-sec-ix-hidden:Fact_7b05dc571fcb46f8bbbe0db51a44d460"&gt;a&lt;/span&gt; medicine for multiple system atrophy (ION464) and &lt;span style="-sec-ix-hidden:Fact_33617a5e2de04e8688f1a06dd038ea29"&gt;a&lt;/span&gt; medicine for an undisclosed target. In the fourth quarter of 2018, Biogen exercised its option to license our most advanced ALS medicine, tofersen, our medicine in Phase 3 development for SOD1 ALS. As a result, Biogen is now responsible for global development, regulatory and commercialization activities and costs for tofersen.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;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. For each antisense molecule that is chosen for drug discovery and development under this collaboration, we are eligible to receive up to approximately $260 million in a license fee and milestone payments per program. The $260 million per program consists of approximately $60 million in development milestones, including amounts related to the cost of clinical trials, and up to $130 million in milestone payments if Biogen achieves pre-specified regulatory milestones. In addition, we are eligible to receive tiered royalties up to the mid-teens on net sales from any antisense medicines developed under this collaboration. From inception through December 2020, we have received over $270 million in upfront fees, milestone payments and other payments under this collaboration. We will achieve the next payment of up to $10 million if we advance a program 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;In the third quarter of 2019, we updated our estimate of the total effort we expect to expend to satisfy our performance obligation. As a result, we recorded a cumulative catch up adjustment of $16.5 million to decrease revenue in the third quarter of 2019. During 2020, we completed our remaining&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; research and development services and recognized the remaining revenue related to this performance obligation. &lt;/span&gt;From inception through the completion of our R&amp;amp;D services performance obligation in &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;2020&lt;/span&gt;, 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;Under this collaboration, we have also generated additional payments that we concluded were not part of our R&amp;amp;D services performance obligation. We recognized each of these payments in full in the respective quarter we generated the payment because we did not have any performance obligations for the respective payment. The following are the payments we earned:&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="zbadc2a2f9de14e398c3088ef55129f4b" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; 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;In the third quarter of 2018, we earned a $10 million milestone payment when Biogen initiated a Phase 1 study of IONIS-C9&lt;sub&gt;Rx&lt;/sub&gt;.&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z751ae1a2bbe04434886f78c55da5aed0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; 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;In the fourth quarter of 2018, we earned a $35 million license fee when Biogen licensed tofersen from us because Biogen had full use of the licenses without any continuing involvement from us.&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z6fa2ded94c1b402e8e872dfa013d9c20" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; 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;In the fourth quarter of 2018, we earned &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;a $&lt;/span&gt;5&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million milestone when Biogen initiated a Proof-of-Concept study for tofersen.&lt;/span&gt;&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z526a9a64e4fa45878f78f5f29010b15c" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; 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;In the third quarter of 2019, we earned an $8 million milestone payment when Biogen initiated a Phase 1/2 study of ION859 &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;for the treatment of people with Parkinson&#x2019;s disease &lt;/span&gt;under this collaboration.&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z1262dc6bc2e54fb5add1931dc4ea3baa" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; 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;In the fourth quarter of 2019, we earned a $10 million milestone payment when Biogen advanced IONIS-C9&lt;sub&gt;Rx&lt;/sub&gt;.&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="zc5ea93483ad7438e826e674c52576e94" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; 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;In the third quarter of 2020, we earned $18 million in milestone payments when Biogen initiated&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; a Phase 1/2 trial for ION464, an investigational medicine in development targeting alpha-synuclein to treat patients with multiple system atrophy.&lt;/span&gt;&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z7a3bf6caaf324953b8dacbd004c6abc7" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; 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;In the third quarter of 2020, w&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;e earned a $&lt;/span&gt;10&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million milestone payment when Biogen initiated a Phase 1/2 trial for ION541, an investigational medicine in development targeting ataxin 2 to treat patients with ALS.&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; font-style: italic;"&gt;2012 Neurology&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In December 2012, we and Biogen entered into a collaboration agreement to develop and commercialize novel antisense medicines to treat neurodegenerative diseases. We are responsible for the development of each of the medicines through the completion of the initial Phase 2 clinical study for such medicine. Biogen has the option to license a medicine from each of the programs through the completion of the first Phase 2 study for each program. Under this collaboration, we are currently advancing IONIS-MAPT&lt;sub&gt;Rx&lt;/sub&gt; for Alzheimer&#x2019;s disease and ION582 for Angelman syndrome. If Biogen exercises its option to license a medicine, it will assume global development, regulatory and commercialization responsibilities and costs for that medicine. In the fourth quarter of 2019, Biogen exercised its option to license IONIS-MAPT&lt;sub&gt;Rx&lt;/sub&gt;. We are responsible for completing the Phase 1/2 in study patients with mild AD and a one-year long-term extension study. Biogen will have responsibility 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. Over the term of the collaboration, we are eligible to receive up to $&lt;/span&gt;210&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million in a license fee and milestone payments per program, plus a mark-up on the cost estimate of the Phase 1 and 2 studies. The $&lt;/span&gt;210&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million per program consists of 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, plus a mark-up on the cost estimate of the Phase 1 and 2 studies and up to $&lt;/span&gt;130&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million in milestone payments if Biogen achieves pre-specified regulatory milestones. 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;three&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; programs. From inception through December 2020, we have received $&lt;/span&gt;154&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million in payments under this collaboration, including $&lt;/span&gt;19.5&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million we received from Biogen for achieving milestones for advancing IONIS-MAPT&lt;/span&gt;&lt;sub&gt;Rx &lt;/sub&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;during 2020. We will achieve the next payment of $&lt;/span&gt;25&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&#160;&lt;/span&gt;million if we continue to advance 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;Under our collaboration, we determined we had a performance obligation to perform R&amp;amp;D services. We allocated $40 million in total payments to the transaction price for our R&amp;amp;D services performance obligation. In the third quarter of 2019, we completed our R&amp;amp;D services performance obligation when we designated a development candidate and Biogen accepted the development candidate. Biogen&#x2019;s decision to accept the development candidate was not within our control. We were recognizing revenue as we performed services based on our effort to satisfy our performance obligation relative to the total effort expected to satisfy our performance obligation. Because Biogen accepted the development candidate earlier than when we were previously estimating, we recognized $6.3 million of accelerated revenue in the third quarter 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;When we commenced development for IONIS-MAPT&lt;sub&gt;Rx&lt;/sub&gt; we identified our development work as a separate performance obligation. We are recognizing our IONIS-MAPT&lt;sub&gt;Rx&lt;/sub&gt; development performance obligation based on the percentage of completion. From inception through December 2020, we have included $57 million in the transaction price for our IONIS-MAPT&lt;sub&gt;Rx&lt;/sub&gt; development performance obligation. We currently estimate we will satisfy our performance obligation in 2022. Our total transaction price for our IONIS-MAPT&lt;sub&gt;Rx &lt;/sub&gt;development performance obligation includes the following payments we achieved in 2019 and 2020 related to our development work:&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z71d69a9d13b14163a88f7ddf594f4ca2" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; 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;In the second quarter of 2019, we achieved a $7.5 million milestone payment from Biogen when we advanced IONIS-MAPT&lt;sub&gt;Rx&lt;/sub&gt;.&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z2fb7af2b8d8f4262bf2f6c66a12e661a" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; 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;In the fourth quarter of 2019, we achieved a $12 million milestone payment from Biogen when we entered into an agreement to conduct a long-term extension study for IONIS-MAPT&lt;sub&gt;Rx&lt;/sub&gt;.&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="zebd2ef566e6449fdbc9e8c4970dcbff2" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; 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;In the first quarter of 2020, we achieved a $7.5 million milestone payment from Biogen when we advanced IONIS-MAPT&lt;sub&gt;Rx&lt;/sub&gt;.&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="zb1d29696a2084872b89e3dda5486ea7e" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; 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;In the third quarter of 2020, we achieved a $12 million milestone payment from Biogen when we advanced IONIS-MAPT&lt;sub&gt;Rx&lt;/sub&gt; in the long-term extension study for IONIS-MAPT&lt;sub&gt;Rx&lt;/sub&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;In the fourth quarter of 2019, we identified another performance obligation upon Biogen&#x2019;s license of IONIS-MAPT&lt;sub&gt;Rx&lt;/sub&gt; because the license we granted to Biogen is distinct from our other performance obligations. We recognized the $45 million license fee for IONIS-MAPT&lt;sub&gt;Rx&lt;/sub&gt; as revenue at that time because Biogen had full use of the license without any continuing involvement from us. Additionally, we did not have any further performance obligations related to the license after we delivered it to Biogen.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In the fourth quarter of 2019, we &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;earned a $&lt;/span&gt;10&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million milestone payment when Biogen advanced ION582. We recognized this milestone payment in full in the fourth quarter of 2019 because we did not have any performance obligations related to this milestone payment.&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;During the years ended December 31, 2020, 2019 and 2018, we earned the following revenue from our relationship with Biogen (in millions, except percentage amounts):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" id="zd7d425e573df43b78d3759c789ce4860" 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;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/&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;2020&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2019&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; 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;2018&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -27pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;SPINRAZA royalties (commercial revenue)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;286.6&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;293.0&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;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;237.9&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 64%; padding-bottom: 2px;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;R&amp;amp;D revenue&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;122.0&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;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;180.6&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;137.1&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total revenue from our relationship with Biogen&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;408.6&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;473.6&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;375.0&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 64%;" valign="bottom"&gt;&lt;div style="text-align: left; 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;56&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;42&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times 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;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;&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 sheet at &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;December 31, &lt;/span&gt;2020&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; and &lt;/span&gt;2019&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; included deferred revenue of $&lt;/span&gt;465.8&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million and $&lt;/span&gt;525.8&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: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Research, Development and Commercialization Partners&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;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;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 have two collaborations with AstraZeneca, one focused on the treatment of cardiovascular, renal and metabolic diseases and a &lt;span style="-sec-ix-hidden:Fact_bba64ca284c648c3b9f851d0da94ba68"&gt;second&lt;/span&gt; focused on the treatment of oncology diseases. We and AstraZeneca are currently developing several investigational medicines under these collaborations, including medicines in development to treat people with cardiovascular disease, a genetically associated form of kidney disease, &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;nonalcoholic steatohepatitis, or NASH, and cancer&lt;/span&gt;. From inception through December 2020, we have received more than $380 million from our AstraZeneca 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: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;&#160;Cardiovascular, Renal and Metabolic Diseases 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 July 2015, we and AstraZeneca formed a collaboration to discover and develop antisense therapies for treating cardiovascular, renal and metabolic diseases. Under our collaboration, AstraZeneca has licensed four medicines from us:&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="za7c7349b939246b39fa9e2aa19d77e94" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; 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;ION449 (formerly IONIS-AZ4-2.5-L&lt;sub&gt;Rx&lt;/sub&gt;), an investigational medicine we designed to reduce the liver production of PCSK9 and lower the plasma level of LDL-C and thus reduce the risk of cardiovascular disease;&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z2dfdbdd62d294421a7273fe5e35037c3" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; 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;ION532, an investigational medicine we designed to reduce the production of APOL1 for the &lt;/span&gt;treatment of APOL1-associated chronic kidney disease;&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z0a6886f2c7d84dda9fde2a2f759cc878" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; 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;ION839, an investigational medicine we designed to &lt;/span&gt;inhibit the production of PNPLA3 protein, a major genetic determinant of NASH progression&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;; and&lt;/span&gt;&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z002dc6aeb8bc422296e6d56b98c4ccce" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; 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;ION455, an investigational medicine we designed as a potential treatment for NASH.&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;AstraZeneca is responsible for global development, regulatory and commercialization activities and costs for each of the medicines it has licensed and any medicines AstraZeneca licenses 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;Under the terms of the agreement, we received a $65 million upfront payment. We are eligible to receive license fees and milestone payments of up to more than $5.5 billion as medicines under this collaboration advance, including up to $1.1 billion for the achievement of development milestones, up to $2.9 billion for regulatory milestones and up to $1.5 billion for commercial milestones. In addition, we are eligible to receive tiered royalties up to the low teens on net sales from any product that AstraZeneca successfully commercializes under this collaboration agreement. We will achieve the next payment of up to $30 million under this collaboration if AstraZeneca advances a medicine under this collaboration&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;.&lt;/span&gt; From inception through December 2020, we have received over $235 million in upfront fees, license fees, milestone payments, and other payments under this collaboration, including $30 million we earned in 2020 when AstraZeneca licensed ION455 and $30 million in milestone payments we earned in 2020 when AstraZeneca advanced ION532 and ION449 in development.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&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 are recognizing revenue for our R&amp;amp;D services performance obligation as we perform 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; currently estimate we will satisfy this performance obligation in&lt;/span&gt; the third quarter of 2021. 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. From inception through December&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; 2020&lt;/span&gt;, we have included $90 million in payments in the transaction price for our R&amp;amp;D services performance obligation.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Under this collaboration, we have also generated additional payments that we concluded were not part of our R&amp;amp;D services performance obligation. We recognized each of these payments in full in the respective quarter we generated the payment because the payments were distinct and we did not have any performance obligations for the respective payment. The following are the payments we have earned:&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z0ae7023b788a477a8ee3164fd8468aa7" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; 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;In the first quarter of 2018, we earned &lt;/span&gt;two&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&#160;&lt;/span&gt;$30 million license fees when AstraZeneca licensed ION532 and ION839 because AstraZeneca had full use of the licenses without any continuing involvement from us.&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="zbd22b188d7d141118d6acbb899d46a1f" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; 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;In the third quarter of 2018, we earned a $10 million milestone payment when AstraZeneca initiated a Phase 1 study of ION449.&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z8c9358f9436c4202896a2813cb0f3f39" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; 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;In the fourth quarter of 2019, we earned a $10 million milestone payment when AstraZeneca initiated a Phase 1 study of ION839.&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z9a1e3b8058ca4604892bb902782a34a9" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; 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;In the first quarter of 2020, we earned a $10 million milestone payment when AstraZeneca advanced ION532.&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z5a522c1fe83848f8801d15aff6f95263" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; 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;In the fourth quarter of 2020, we earned a $20 million milestone payment when AstraZeneca advanced ION449.&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="zbf207a3eb3f941749b4dcfc7d039a507" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; 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;In the fourth quarter of 2020, we earned a &lt;/span&gt;$30 million license fee when AstraZeneca licensed ION455 because AstraZeneca had full use of the license without any continuing involvement from us.&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: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Oncology Collaboration&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In December 2012, we entered into a collaboration agreement with AstraZeneca to discover and develop antisense medicines to treat cancer. We and AstraZeneca also established an oncology research program. AstraZeneca has the option to license medicines resulting from the program, and if AstraZeneca exercises its option to license a medicine, it will be responsible for global development, regulatory and commercialization activities and costs for such medicine. In 2020, AstraZeneca licensed ION736, an investigational medicine in development targeting FOXP3 for the treatment of cancer.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&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 this agreement, we received $&lt;/span&gt;31&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million in upfront payments. We are eligible to receive milestone payments and license fees up to more than $&lt;/span&gt;265&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million under this collaboration, including up to $&lt;/span&gt;107&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million for the achievement of development milestones and up to $&lt;/span&gt;105&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million for the achievement of regulatory milestones. 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 2020, we have received over $&lt;/span&gt;140&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million in upfront fees, milestone payments, and other payments under this oncology collaboration, including $&lt;/span&gt;13&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million we earned when AstraZeneca licensed&lt;/span&gt; ION736 in 2020. We &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;will achieve the next payment of $&lt;/span&gt;12&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million &lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;if AstraZeneca advances ION736 in development.&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 completed all of the performance obligations we identified under this collaboration in the first quarter of 2018.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Under this collaboration, we have also generated additional payments that we concluded were not part of other performance obligations discussed above. We recognized each of these payments in full in the respective quarter we generated the payment because the payments were distinct and we did not have any performance obligations for the respective payment. The following are the payments we have earned:&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z2bdcc0a9c35d483d9c8c7f4a41bc0cfb" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; 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;In the fourth quarter of 2018, we earned a $17.5 million milestone payment and a $10 million milestone payment when AstraZeneca advanced two programs under our collaboration.&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z79487d3e861444efb73a94ea6625d8c5" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; 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;In the second quarter of 2020, we earned a $&lt;/span&gt;13&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million license fee when AstraZeneca licensed ION736&lt;/span&gt; because AstraZeneca had full use of the license without any continuing involvement from us.&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;During the years ended December 31, 2020, 2019 and 2018, we earned the following revenue from our relationship with AstraZeneca (in millions, except percentage amounts):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" id="z01afabad46534511a6a9d546d3508d28" 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;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/&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;2020&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2019&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; 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;2018&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -27pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;R&amp;amp;D revenue&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;88.0&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;28.1&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;120.7&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;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;12&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;3&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;20&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&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 sheet at &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;December 31, &lt;/span&gt;2020&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; and &lt;/span&gt;2019&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; included deferred revenue of $&lt;/span&gt;10.0&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million and $&lt;/span&gt;25.0&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million, respectively, related to our relationship with AstraZeneca.&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;Bayer&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&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 May 2015, we entered into an exclusive license agreement with Bayer to develop and commercialize IONIS-FXI&lt;sub&gt;Rx&lt;/sub&gt; for the prevention of thrombosis. We were responsible for completing a Phase 2 study of IONIS-FXI&lt;sub&gt;Rx&lt;/sub&gt; in people with end-stage renal disease on hemodialysis. Under the terms of the agreement, we received a $100 million upfront payment in the second quarter of 2015. In February 2017, we amended our agreement with Bayer to advance IONIS-FXI&lt;sub&gt;Rx&lt;/sub&gt; and to initiate development of IONIS-FXI-L&lt;sub&gt;Rx&lt;/sub&gt;, which Bayer licensed. In conjunction with the decision to advance these programs, we received a $75 million payment from Bayer. In October 2019, Bayer decided it would advance IONIS-FXI-L&lt;sub&gt;Rx&lt;/sub&gt; following positive clinical results. Bayer is now responsible for all global development, regulatory and commercialization activities and costs for the FXI 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 are eligible to receive up to $385 million in license fees, milestone payments and other payments, including up to $125 million for the achievement of development milestones and up to $110 million for the achievement of commercialization milestones. In addition, we are eligible to receive tiered royalties in the low to high 20 percent range on gross margins of both medicines combined. From inception through December 2020, we have received over $185 million from this collaboration. We will achieve the next payment of $20 million if Bayer initiates a Phase 3 study for the FXI 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;At the commencement of this collaboration, we identified three performance obligations, the license of IONIS-FXI&lt;sub&gt;Rx&lt;/sub&gt;, R&amp;amp;D services and delivery of API, all of which we completed in 2016.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&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 February 2017, when we amended our collaboration with Bayer, we identified two new performance obligations&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;, &lt;/span&gt;one&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; for the license of IONIS-FXI-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; and &lt;/span&gt;one&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; for R&amp;amp;D services&lt;/span&gt;. We determined the transaction price to be the $75 million payment. We allocated $64.9 million to &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;the license of IONIS-FXI-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; based on its estimated relative stand-alone selling price and recognized the associated revenue upon our delivery of the license in the first quarter of 2017. We allocated $&lt;/span&gt;10.1&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million to our R&amp;amp;D services performance obligation based on an estimated relative stand-alone selling price. &lt;/span&gt;We recognized revenue for our R&amp;amp;D services performance obligation as we performed services based on our effort to satisfy our performance obligation relative to our total effort expected to satisfy our performance obligation. We completed our obligation in the third quarter 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;In the fourth quarter of 2019, we earned a $10 million milestone payment when Bayer decided it would advance IONIS-FXI-L&lt;sub&gt;Rx&lt;/sub&gt;. We recognized this milestone payment in full in the fourth quarter of 2019 because we did not have any performance obligations related to this milestone payment.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;During the years ended December 31, 2020, 2019 and 2018, we earned the following revenue from our relationship with Bayer (in millions, except percentage amounts):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" id="z9c944936e6cb48bf94b3cd80005a253e" 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;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/&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;2020&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2019&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; 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;2018&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -27pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;R&amp;amp;D revenue&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;3.2&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;14.3&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;5.0&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 64%;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Percentage of total revenue&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;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;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;1&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Our consolidated balance sheet at December 31, &lt;/span&gt;2020&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; did &lt;/span&gt;no&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;t include any deferred revenue related to our relationship with Bayer. Our &lt;/span&gt;consolidated balance sheet at &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;December 31, &lt;/span&gt;2019&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; included deferred revenue of $&lt;/span&gt;2.4&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million related to our relationship with Bayer.&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;GSK&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In March 2010, we entered into an alliance with GSK using our antisense drug discovery platform to discover and develop new medicines against targets for serious and rare diseases, including infectious diseases and some conditions causing blindness. Under the terms of the agreement, we received upfront payments of $35 million. Our collaboration with GSK currently includes two medicines targeting hepatitis B virus, or HBV: IONIS-HBV&lt;sub&gt;Rx&lt;/sub&gt; and IONIS-HBV-L&lt;sub&gt;Rx&lt;/sub&gt;. We designed these medicines to reduce the production of viral proteins associated with HBV infection. In the third quarter of 2019, following positive Phase 2 results, GSK licensed our HBV program. GSK is responsible for all global development, regulatory and commercialization activities and costs for the HBV program.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Under our agreement, if GSK successfully develops these medicines and achieves pre-agreed sales targets, we could receive license fees and milestone payments of up to $262 million, including up to $47.5 million for the achievement of development milestones, up to $120 million for the achievement of regulatory milestones and up to $70 million for the achievement of commercialization milestones. In addition, we are eligible to receive tiered royalties up to the mid-teens on net sales from any product that GSK successfully commercializes under this alliance. From inception through December 2020, we have received more than $190 million in payments under this alliance with GSK. We will achieve the next payment of $15 million if GSK initiates a Phase 3 study of a medicine under this 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;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We completed our R&amp;amp;D services performance obligations under our collaboration in the first quarter of 2015. &lt;/span&gt;We identified a new performance obligation when we granted GSK the license of the HBV program and assigned related intellectual property rights in the third quarter of 2019 because the license was distinct from our other performance obligations. We recognized the $25 million license fee for the HBV program as revenue at that time because GSK had full use of the license without any continuing involvement from us. Additionally, we did not have any further performance obligations related to the license after we delivered it to GSK.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We do not have any remaining performance obligations under our collaboration with GSK; however, we can still earn additional payments and royalties as GSK advances the HBV program.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&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, 2020, 2019 and 2018, we earned the following revenue from our relationship with GSK (in millions, except percentage amounts):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" id="zd82f932b4364444296f6727d4a1a1d5e" 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;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/&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;2020&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2019&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; 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;2018&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -27pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;R&amp;amp;D revenue&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.2&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;25.4&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1.6&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 64%;" valign="bottom"&gt;&lt;div style="text-align: left; 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;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;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;/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, 2020 and 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; font-style: italic;"&gt;Janssen Biotech, 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;In December 2014, we entered into a collaboration agreement with Janssen Biotech, Inc. to discover and develop antisense medicines that can be locally administered, including oral delivery, to treat autoimmune disorders of the GI tract. Under our collaboration, Janssen is currently advancing ION253 for the treatment of immune-mediated GI disease. Janssen licensed ION253 in the fourth quarter of 2017. Prior to Janssen&#x2019;s license of ION253, we were responsible for the discovery activities to identify development candidates. Under the agreement, Janssen is responsible for global development, regulatory and commercialization activities and costs for ION253.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&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 $35 million in upfront payments. We are eligible to receive up to more than $285 million in license fees and milestone payments for these programs, including up to $65 million for the achievement of development milestones, up to $160 million for the achievement of regulatory milestones and up to $60 million for the achievement of commercialization milestones. From inception through December 2020, we have received over $80 million from this collaboration. In addition, we are eligible to receive tiered royalties up to the near teens on net sales from any medicines resulting from this collaboration. We will achieve the next payment of $5 million if Janssen continues to advance ION253 in development.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&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 Janssen. We determined the transaction price to be the $35 million upfront payments we received. We allocated the &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/span&gt;35&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million&lt;/span&gt; to our single performance obligation. As we achieved milestone payments for our R&amp;amp;D services, we included these amounts in our transaction price for our R&amp;amp;D services performance obligation. We recognized revenue for our R&amp;amp;D services performance obligation over our period of performance, which ended in the fourth quarter of 2017.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Under this collaboration, we have also generated additional payments that we concluded were not part of our R&amp;amp;D services performance obligation. We recognized each of these payments in full in the respective quarter in which we generated the payment because the payments were distinct and we did not have any performance obligations for the respective payment. In the third quarter of 2020, we earned a $&lt;/span&gt;5&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million milestone payment when Janssen initiated a Phase 1 trial for ION253&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, 2020, 2019 and 2018, we earned the following revenue from our relationship with Janssen (in millions, except percentage amounts):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" id="z214ec07483da45419ff12bf6494b6cc8" 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;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/&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;2020&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2019&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; 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;2018&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -27pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;R&amp;amp;D revenue&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;5.0&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-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;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;6.6&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 64%;" valign="bottom"&gt;&lt;div style="text-align: left; 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;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;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;1&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We did not have any deferred revenue from our relationship with Janssen at December 31, 2020 and 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; font-style: italic;"&gt;Novartis&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;In January 2017, we initiated a collaboration with Novartis to develop and commercialize pelacarsen and IONIS-APOCIII-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;.&lt;/span&gt;&lt;sub&gt;&#160;&lt;/sub&gt;We received a $75 million upfront payment in the first quarter of 2017. &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;In the first quarter of 2019, Novartis licensed pelacarsen&lt;/span&gt; and we earned a $150 million license fee. Novartis is responsible for conducting and funding future development and regulatory activities for pelacarsen, including a global Phase 3 cardiovascular outcomes study that Novartis initiated in the fourth quarter 2019.&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&#160;&lt;/span&gt;In connection with Novartis&#x2019; license of pelacarsen, we and Novartis established a more definitive framework under which the companies would negotiate the co-commercialization of pelacarsen in selected markets. Included in this framework is an option by which Novartis could solely commercialize pelacarsen in exchange for Novartis paying us increased sales milestone payments based on sales of pelacarsen.&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&#160;&lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;When Novartis decided to not exercise its option for &lt;/span&gt;IONIS-APOCIII-L&lt;sub&gt;Rx&lt;/sub&gt;, we retained rights to develop and commercialize IONIS-APOCIII-L&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;Under the collaboration, we are eligible to receive up to $675 million in milestone payments, including $25 million for the achievement of a development milestone, up to $290 million for the achievement of regulatory milestones and up to $360 million for the achievement of commercialization milestones. &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;From inception through December 2020, we have received $&lt;/span&gt;249&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million in upfront payments, milestone payments, license fees and other payments from this collaboration. &lt;/span&gt;We are also eligible to receive tiered royalties in the mid-teens to low 20 percent range on net sales of pelacarsen. &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We&lt;/span&gt;&lt;span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; will achieve the next payment of $&lt;/span&gt;25&lt;span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million if Novartis advances pelacarsen.&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In conjunction with this collaboration, we entered into a SPA with Novartis. As part of the SPA, Novartis purchased 1.6 million shares of our common stock for $100 million in the first quarter of 2017. As part of the SPA, Novartis was required to purchase $50 million of Akcea&#x2019;s common stock at Akcea&#x2019;s IPO price or our common stock at a premium if an IPO did not occur by April 2018. Under the SPA, in the second quarter of 2017, Novartis purchased $50 million of Akcea&#x2019;s common stock in a separate private placement concurrent with the completion of Akcea&#x2019;s IPO at a price per share equal to the IPO 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;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" id="z96b1240939864a0aa59d9ebe41065fe9" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; 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" id="z3d70c236552f4ba28ef26a97261216f0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; 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 IONIS-APOCIII-L&lt;sub&gt;Rx&lt;/sub&gt;;&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="ze5c0c7016a924d6cacedb4f5ac960dfd" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; 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" id="zdb1bac79654341e49628adcdaa4ae22a" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; 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 IONIS-APOCIII-L&lt;sub&gt;Rx&lt;/sub&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;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" id="z121d185a2fd2440eb0afde6cd75e4546" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; 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" id="zb9c0424c697141e98b124b59cc86ef6e" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$28.4 million for the premium paid by Novartis for its purchase of our common stock at a premium in the first quarter of 2017; and&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z9ccebd2e3ba84fa4b417d18915d23207" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; 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" id="zd02b83fa42c4476fa906790b9a6cedc0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; 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 &lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;pelacarsen;&lt;/span&gt;&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z797fd60954dd4557b52fbeff3a842394" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; 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;IONIS-APOCIII-L&lt;/span&gt;&lt;sub style="font-family: 'Times New Roman';"&gt;Rx&lt;/sub&gt;; &lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="zde031348d3aa4afdbd2863fd76fd398b" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; 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;&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" id="z8d4ab36eb2c14f349a1e5abf6e78ce98" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; 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;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;2.8&lt;/span&gt; million for the delivery of IONIS-APOCIII-L&lt;sub&gt;Rx&lt;/sub&gt; 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 recognized revenue related to each of the performance obligations as follows:&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z07ee17717ec44cdfadce3eff5cb75de7" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; 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 completed our R&amp;amp;D services performance obligation for pelacarsen&lt;sub&gt;&#160;&lt;/sub&gt;in second quarter of 2019. As such, we recognized all revenue we allocated to the pelacarsen&lt;sub&gt;&#160;&lt;/sub&gt;R&amp;amp;D services as of the end of the second quarter of 2019;&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="ze87ab810b8c24867a4976ca1df80ead9" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; 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 completed our R&amp;amp;D services performance obligation for IONIS-APOCIII-L&lt;sub&gt;Rx&lt;/sub&gt; in the fourth quarter of 2019 because Novartis elected to terminate the strategic collaboration for IONIS-APOCIII-L&lt;sub&gt;Rx&lt;/sub&gt; during the period. As a result, we were not required to provide any further R&amp;amp;D services, as such, we recognized all revenue allocated to the IONIS-APOCIII-L&lt;sub&gt;Rx&lt;/sub&gt; R&amp;amp;D services as of the end of the fourth quarter of 2019;&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z0733e5bad35c4e1399d772ddddac80e6" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; 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 recognized the amount attributed to pelacarsen API when we delivered it to Novartis in 2017; and&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="zc5fa7220e2ed4db0afb1d000146ea46c" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; 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 recognized the amount attributed to IONIS-APOCIII-L&lt;sub&gt;Rx&lt;/sub&gt; API when we delivered it to Novartis in the second quarter of 2018.&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 recognized revenue related to the R&amp;amp;D services for pelacarsen and IONIS-APOCIII-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; performance obligations as we performed services &lt;/span&gt;based on our effort to satisfy our performance obligations relative to our total effort expected to satisfy our performance obligations&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;.&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;During the years ended December 31, 2020 and 2019, we earned the following revenue from our relationship with Novartis (in millions, except percentage amounts):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" id="zbc240042123541949eac40f85586e85a" 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;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/&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;2020&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2019&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; 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;2018&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -27pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;R&amp;amp;D revenue&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1.0&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;187.4&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;50.6&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 64%;" valign="bottom"&gt;&lt;div style="text-align: left; 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;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;17&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times 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;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;/tr&gt;
&lt;/table&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We did not have any deferred revenue from our relationship with Novartis at December 31, 2020 and 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: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Pfizer&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&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 October 2019, we entered into a license agreement with Pfizer for vupanorsen, an investigational medicine in development to treat people with certain cardiovascular diseases. We completed a Phase 2 study of vupanorsen in patients&lt;/span&gt; with elevated levels of triglycerides, or hypertriglyceridemia, type 2 diabetes and &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;NAFLD. Pfizer is responsible for all global development, regulatory and commercialization activities and costs for vupanorsen, subject to our right to co-commercialize in the U.S. and certain additional markets.&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;Under the terms of the agreement, we received a $&lt;/span&gt;250&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million upfront payment. We are also eligible to receive development, regulatory and sales milestone payments of up to $&lt;/span&gt;1.3&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; billion&lt;/span&gt;, including up to $205 million for the achievement of development milestones, up to $250 million for the achievement of regulatory milestones and up to $850 million for the achievement of commercialization milestones. &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;From inception through December 2020, we have received over $&lt;/span&gt;330&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million, including a $&lt;/span&gt;75&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million milestone payment we earned in the fourth quarter of 2020 when Pfizer began the Phase 2b study of vupanorsen. &lt;/span&gt;We are&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; also eligible to earn tiered royalties in the mid-teens to low &lt;/span&gt;20 percent&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; range on annual worldwide net sales. Prior to regulatory filing for marketing approval, we have the right, at our option to participate in certain commercialization activities with Pfizer in the U.S. and certain additional markets on pre-defined terms and based on meeting pre-defined criteria. 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 Pfizer advances vupanorsen.&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 the license agreement, we identified three separate performance obligations:&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="zd5bad646b7e448a3a9fe0f3ca3c6c245" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; 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;License of vupanorsen;&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z0f346714db2e4d08bcd013533066c0cc" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; 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 vupanorsen; and&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="ze9f95e2f073b4cbf8e0854f2741778f8" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; 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 vupanorsen.&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 the transaction price to be $250 million, the upfront payment we received.&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; We &lt;/span&gt;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" id="z41311be7633d461192f4fe74ca293c01" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; 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;$245.6 million for the license of vupanorsen;&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z4e228f251e304158a2d73dced6a689f4" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; 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;2.2&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million for the R&amp;amp;D services for &lt;/span&gt;vupanorsen&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;; and&lt;/span&gt;&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z09d754cd2883400894b04f43113ed981" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; 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;2.2&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million for the delivery of &lt;/span&gt;vupanorsen&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; API.&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;We are recognizing revenue related to each of our performance obligations as follows:&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z5049f3a6226d4187bf650e164ea1c247" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; 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 recognized $245.6 million for the license of vupanorsen in the fourth quarter of 2019 because we determined the license we granted to Pfizer was distinct from our other performance obligations and Pfizer had full use of the license without any continuing involvement from us.&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z371608c9e0fe48d3a2f97c25050c0b35" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; 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 &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;recognized revenue related to the R&amp;amp;D services for &lt;/span&gt;vupanorsen&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; as we performed services &lt;/span&gt;based on our effort to satisfy our performance obligation relative to our total effort to satisfy our performance obligation&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;. We completed our R&amp;amp;D services in &lt;/span&gt;mid-2020&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;.&lt;/span&gt;&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="zcf939c7c945446388558c20dd6e65f46" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; 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&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; recognized the amount attributed to the API supply for &lt;/span&gt;vupanorsen&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; when we delivered it to Pfizer in the fourth quarter of 2019.&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;In the fourth quarter of 2020, we earned a $75 million milestone payment when Pfizer began the Phase 2b study of vupanorsen. We recognized this milestone payment in full in the fourth quarter of 2020 because we did not have any performance obligations related to this milestone payment.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;During the years ended December 31, 2020 and 2019, we earned the following revenue from our relationship with Pfizer (in millions, except percentage amounts):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" id="z6cd9b1a78b1f4646b6991f4b40434cd7" 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;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/&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;2020&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2019&lt;/div&gt;&lt;/td&gt;
    &lt;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: -27pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;R&amp;amp;D revenue&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;82.1&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;248.7&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;tr&gt;
    &lt;td style="vertical-align: bottom; width: 76%;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Percentage of total revenue&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;11&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;22&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&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;We did &lt;/span&gt;no&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;t have any deferred revenue from our relationship with Pfizer at December 31, &lt;/span&gt;2020&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;. Our &lt;/span&gt;consolidated balance sheet at &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;December 31, 2019 included deferred revenue of $&lt;/span&gt;1.3&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million related to our relationship with Pfizer.&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;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;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 up to $26 million in payments. From inception through December 2020, we have received $22 million from PTC. We are eligible to receive royalties from PTC in the mid-20 percent range on net sales in Latin America for each medicine. PTC&#x2019;s obligation to pay us royalties begins on the earlier of 12 months after the first commercial sale of a product in Brazil or the date that PTC recognizes revenue of at least $10 million in Latin America.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In the third quarter of 2018 at the commencement of this collaboration, we identified two performance obligations, which were the licenses we granted to PTC to commercialize TEGSEDI and WAYLIVRA in Latin America and certain Caribbean countries. We recognized $12 million in license fee revenue at that time because PTC had full use of both licenses without any continuing involvement from us. We do not have any remaining performance obligations under our collaboration with PTC. We can still earn additional payments and royalties as PTC commercializes TEGSEDI and WAYLIVRA.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&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 milestone payments that we concluded were not part of the performance obligations discussed above. We recognized each of these milestone payments in full in the respective quarter in which we achieved the milestone payment because the payments were distinct and we did not have any performance obligations for the respective payment. The following are the payments we have earned:&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z4abce04efa244e55b617be785e66be12" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; 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;In the second quarter of 2019, we earned a $6 million payment when WAYLIVRA was approved by the EMA.&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="za7c3c78f718a4ad8a301c4be154c8a67" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; 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;In the fourth quarter of 2019, we earned $4 million when TEGSEDI was approved in Brazil.&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;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; &lt;/span&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;During the years ended December 31, 2020, 2019 and 2018, we earned the following revenue from our relationship with PTC (in millions, except percentage amounts):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" id="z00af651f87dd4ff3a8aa829ed62a0b47" 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;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/&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;2020&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2019&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; 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;2018&lt;/div&gt;&lt;/td&gt;
    &lt;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;Licensing and other royalty revenue (commercial revenue)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1.6&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;10.2&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;12.0&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 64%;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Percentage of total revenue&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;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;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;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;Our consolidated balance sheet at December 31, 2020 and 2019 did not include any deferred revenue related to our relationship with 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: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Roche&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="text-align: left; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Huntington&#x2019;s Disease&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In April 2013, we formed an alliance with Hoffman-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 in Phase 3 development. We developed tominersen through completion of our Phase 1/2 clinical study in people with early stage HD. In the fourth quarter of 2017, upon completion of the Phase 1/2 study, Roche exercised its option to license tominersen. Roche is responsible for all global development, regulatory and commercialization activities and costs for tominersen.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Under the terms of the agreement, we received an upfront payment of $30 million in April 2013 and an additional $3 million payment in 2017. We are eligible to receive up to $365 million in a license fee and milestone payments including up to $70 million for the achievement of development milestones, up to $170 million for the achievement of regulatory milestones and up to $80 million for the achievement of commercialization milestones. 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 any net sales of any product resulting from this alliance. From inception through December 2020, we have received $150 million in upfront fees, milestone payments and license fees under this collaboration. We will achieve the next payment of $15 million if 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: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;At the commencement of this collaboration, we identified one performance obligation, which was to perform R&amp;amp;D services for Roche. We determined the transaction price to be the $30 million upfront payment we received and allocated it to our single performance obligation. As we achieved milestone payments for our R&amp;amp;D services, we included these amounts in our transaction price for our R&amp;amp;D services performance obligation. We recognized revenue for our R&amp;amp;D services performance obligation over our period of performance, which ended in the third quarter of 2017.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Under this collaboration, we have also generated additional payments that we concluded were not part of our R&amp;amp;D services performance obligation. We recognized each of these payments in full in the respective quarter in which we generated the payment because the payments were distinct and we did not have any performance obligations for the respective payment. The following are the payments we have earned:&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="zf451f16441ea44558aa69cebef8e1675" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; 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;In the fourth quarter of 2017, we earned a $45 million license fee when Roche licensed tominersen because Roche had full use of the license without any continuing involvement from us.&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z00ac98db4efa4864b5d2fa1574c1fc7f" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; 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;In the first quarter of 2019, we earned $35 million in milestone payments when Roche dosed the first patient in the Phase 3 study of tominersen in the first quarter of 2019.&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 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: justify; 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;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;In October 2018, we entered into a collaboration agreement with Roche to&lt;/span&gt;&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;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; for the treatment of complement-mediated diseases. We are currently conducting Phase 2 studies in &lt;/span&gt;two&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; disease indications for &lt;/span&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;Rx&lt;/sub&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;, &lt;/span&gt;one&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; for the treatment of patients with GA, the advanced stage of dry AMD, and a &lt;/span&gt;&lt;span style="-sec-ix-hidden:Fact_04500eaf787641bfbd86183ba9891b89"&gt;second&lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; for the treatment of patients with IgA nephropathy. &lt;/span&gt;Roche&lt;span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; has the option to license 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; at the completion of these studies. Upon licensing, &lt;/span&gt;Roche &lt;span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;will be responsible for global development, regulatory and commercialization activities and 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;&lt;span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Under the terms of this agreement, we received a &lt;/span&gt;$75 million&lt;span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; upfront payment in the fourth quarter of 2018. We are eligible to receive up to &lt;/span&gt;$684 million&lt;span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; in development, regulatory and sales milestone payments and license fees. In addition, we are also eligible to receive tiered royalties from the high teens to &lt;/span&gt;20 percent&lt;span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; on net sales. We will achieve the next payment of $&lt;/span&gt;20&lt;span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million if we advance &lt;/span&gt;the Phase 2 study in patients with dry AMD&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;At the commencement of this collaboration, we identified one performance obligation, which was to perform R&amp;amp;D services for Roche. We determined the transaction price to be the $75 million upfront payment we received and allocated it to our single performance obligation. We are recognizing revenue for our R&amp;amp;D services performance obligation as we perform services based on our effort to satisfy our performance obligation relative to our total effort expected to satisfy our performance obligation. During the fourth quarter of 2020, we &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;updated our estimate of the total effort we expected to expend to satisfy our performance obligation under this collaboration.&lt;/span&gt;&#160;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;In the fourth quarter of 2020, we recorded a cumulative catch up adjustment of $&lt;/span&gt;9.2&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million to decrease revenue because we updated our total cost estimate to complete the Phase 2 study of &lt;/span&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 the &lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;treatment of patients with GA. &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 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, 2020, 2019 and 2018, we earned the following revenue from our relationship with Roche (in millions, except percentage amounts):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" id="za78565dce5c647feb8b04dec8baff53c" 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;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/&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;2020&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2019&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; 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;2018&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -27pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;R&amp;amp;D revenue&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;5.9&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;57.0&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;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;8.3&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/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;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;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;1&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Our &lt;/span&gt;consolidated balance sheet at &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;December 31, &lt;/span&gt;2020&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; and &lt;/span&gt;2019&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; included deferred revenue of $&lt;/span&gt;47.2&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million and $&lt;/span&gt;52.3&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="display:none;"&gt;&lt;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;Other 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;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 exclusively licensed to Alnylam our patent estate relating to antisense motifs and mechanisms and oligonucleotide chemistry for double-stranded RNAi therapeutics in exchange for 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 rights to 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 medicines 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;In the fourth quarter 2020, we completed an arbitration process with Alnylam. The arbitration panel awarded us $41.2 million for payments owed to us by Alnylam related to Alnylam&#x2019;s agreement with Sanofi Genzyme. We recognized the $41.2 million payment from Alnylam as revenue in the fourth quarter of 2020 because we did not have any performance obligations for the respective payment.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" id="ze601d61823704755a02ce987dfe37676" 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;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/&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;2020&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2019&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; 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;2018&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -27pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;R&amp;amp;D revenue&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;47.9&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;24.1&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
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    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
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  &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, 2020 and 2019 did not include any deferred revenue related to our relationship with Alnylam.&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, 2020, 2019 and 2018, we earned the following revenue from our relationship with Biogen (in millions, except percentage amounts):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" id="zd7d425e573df43b78d3759c789ce4860" 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;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/&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;2020&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2019&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; 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;2018&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -27pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;SPINRAZA royalties (commercial revenue)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;286.6&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;293.0&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;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;237.9&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 64%; padding-bottom: 2px;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;R&amp;amp;D revenue&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;122.0&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;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;180.6&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;137.1&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total revenue from our relationship with Biogen&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;408.6&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;473.6&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;375.0&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 64%;" valign="bottom"&gt;&lt;div style="text-align: left; 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;56&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;42&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times 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;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;&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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&lt;div style="display:none;"&gt;&lt;br/&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, 2020, 2019 and 2018, we earned the following revenue from our relationship with AstraZeneca (in millions, except percentage amounts):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" id="z01afabad46534511a6a9d546d3508d28" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&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="10" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Year Ended December 31,&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
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    &lt;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;2020&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2019&lt;/div&gt;&lt;/td&gt;
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    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2018&lt;/div&gt;&lt;/td&gt;
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  &lt;/tr&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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;88.0&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;28.1&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;120.7&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;tr&gt;
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    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
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&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;During the years ended December 31, 2020, 2019 and 2018, we earned the following revenue from our relationship with Bayer (in millions, except percentage amounts):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&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;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
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    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
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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;
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    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
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    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
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&lt;div style="display:none;"&gt;&lt;br/&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, 2020, 2019 and 2018, we earned the following revenue from our relationship with GSK (in millions, except percentage amounts):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

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  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="10" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Year Ended December 31,&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
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    &lt;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;2020&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2019&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;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
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    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
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    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1.6&lt;/div&gt;&lt;/td&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;0&lt;/div&gt;&lt;/td&gt;
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    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2&lt;/div&gt;&lt;/td&gt;
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    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0&lt;/div&gt;&lt;/td&gt;
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&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;During the years ended December 31, 2020, 2019 and 2018, we earned the following revenue from our relationship with Janssen (in millions, except percentage amounts):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&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;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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="display:none;"&gt;&lt;br/&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, 2020 and 2019, we earned the following revenue from our relationship with Novartis (in millions, except percentage amounts):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

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  &lt;tr&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="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;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2020&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2019&lt;/div&gt;&lt;/td&gt;
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    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2018&lt;/div&gt;&lt;/td&gt;
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    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1.0&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;187.4&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;50.6&lt;/div&gt;&lt;/td&gt;
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  &lt;/tr&gt;
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    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0&lt;/div&gt;&lt;/td&gt;
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    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;17&lt;/div&gt;&lt;/td&gt;
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&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;During the years ended December 31, 2020 and 2019, we earned the following revenue from our relationship with Pfizer (in millions, except percentage amounts):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" id="z6cd9b1a78b1f4646b6991f4b40434cd7" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&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;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
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    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
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    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;248.7&lt;/div&gt;&lt;/td&gt;
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  &lt;/tr&gt;
  &lt;tr&gt;
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    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;11&lt;/div&gt;&lt;/td&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;22&lt;/div&gt;&lt;/td&gt;
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  &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, 2020, 2019 and 2018, we earned the following revenue from our relationship with PTC (in millions, except percentage amounts):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&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;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2020&lt;/div&gt;&lt;/td&gt;
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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;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
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    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
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    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
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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;0&lt;/div&gt;&lt;/td&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;1&lt;/div&gt;&lt;/td&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;2&lt;/div&gt;&lt;/td&gt;
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&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;During the years ended December 31, 2020, 2019 and 2018, we earned the following revenue from our relationship with Roche (in millions, except percentage amounts):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

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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;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
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    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
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    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
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    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
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    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-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&lt;/div&gt;&lt;/td&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;1&lt;/div&gt;&lt;/td&gt;
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&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In the fourth quarter 2020, we completed an arbitration process with Alnylam. The arbitration panel awarded us $41.2 million for payments owed to us by Alnylam related to Alnylam&#x2019;s agreement with Sanofi Genzyme. We recognized the $41.2 million payment from Alnylam as revenue in the fourth quarter of 2020 because we did not have any performance obligations for the respective payment.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

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  &lt;tr&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;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
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    &lt;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;2020&lt;/div&gt;&lt;/td&gt;
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    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2019&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; 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;2018&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;R&amp;amp;D revenue&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;47.9&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;24.1&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2.0&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;
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    &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;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&lt;/div&gt;&lt;/td&gt;
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    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
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&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;7. Akcea Acquisition&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;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;Purchase Price and Direct Transaction Costs Accounting for the Akcea Acquisition&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In October 2020, we acquired the shares of Akcea&#x2019;s common stock we did not own, increasing our ownership from 76 percent to 100 percent. Under the purchase agreement, we purchased 24.8 million shares at $18.15 per share, resulting in a total purchase price of $450.6 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;To reflect our 100 percent ownership, we accounted for the increase in our ownership by eliminating the noncontrolling interest adjustment in stockholders&#x2019; equity in accordance with the Consolidation accounting guidance (ASC Topic 810). We recognized the difference between the purchase price and the adjustment to noncontrolling interest in stockholders&#x2019; equity as additional-paid-in capital. Refer to our &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Statement of Stockholders&#x2019; Equity&lt;/span&gt; for detailed amounts.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&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 accounted for the transaction costs related to the Akcea Acquisition as a direct charge to stockholders&#x2019; equity. We incurred $40.6 million of direct transaction costs from the Akcea Acquisition, primarily comprised of banking and legal fees.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;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;Equity Award Payouts related to the Akcea Acquisition&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&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 October 2020, as part of the Akcea Acquisition, Ionis cancelled all of Akcea&#x2019;s equity awards. In exchange for the cancelled awards, if eligible under the terms of the Acquisition, we paid holder&#x2019;s a cash payment. We paid $&lt;/span&gt;18.15&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; for each outstanding RSU. For each outstanding option with an exercise price less than $&lt;/span&gt;18.15&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;, we paid $&lt;/span&gt;18.15&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; less the exercise price. As a result, we paid out $&lt;/span&gt;53.4&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million in the fourth quarter of 2020 related to Akcea&#x2019;s cancelled equity awards. We accounted for these payments as part of the transaction costs recorded to stockholders&#x2019; equity in the fourth quarter of 2020. &lt;/span&gt;Because we did not replace the Akcea awards, we recognized all unrecognized non-cash stock-based compensation ($59.3 million) under Akcea&#x2019;s Plan in our statement of operations in the post-acquisition period in the fourth quarter of 2020.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;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;Severance and Retention Costs related to the Akcea Acquisition&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; margin-top: 2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;As a result of the Akcea Acquisition, we expect to incur severance expenses of up to $9.3 million and retention expenses of up to $19.2 million. During the fourth quarter of 2020, we recorded $15.3 million of severance and retention related costs in operating expenses. We will recognize the remaining severance and retention costs through October 2021.&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; margin-top: 2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The following table summarizes the costs by category related to the Akcea Acquisition (in millions):&lt;/div&gt;

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

&lt;table cellpadding="0" cellspacing="0" id="z1803e5712c1b4b6791766ce6bf566d51" 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;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/&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;Three Months Ended&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, 2020&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 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;R&amp;amp;D 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;3.9&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%; padding-bottom: 2px;" valign="bottom"&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;SG&amp;amp;A 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;11.4&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/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&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;15.3&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; margin-top: 2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The following table summarizes the severance and retention reserve included in accrued compensation for the period indicated related to Akcea Acquisition (in millions):&lt;/div&gt;

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

&lt;table cellpadding="0" cellspacing="0" id="z320d5d0099aa41cba26e4938ee44b076" 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;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/&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;Three Months Ended&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, 2020&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 88%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Severance &amp;amp; retention reserve beginning balance&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;&#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: top; width: 88%;" valign="bottom"&gt;&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Severance &amp;amp; retention expensed during period&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;15.3&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 88%; 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;Amounts paid during the period&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(0.6&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 88%; padding-bottom: 4px;" valign="bottom"&gt;&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Severance &amp;amp; retention reserve ending balance&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;14.7&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; margin-top: 2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The following table summarizes the costs by category related to the Akcea Acquisition (in millions):&lt;/div&gt;

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

&lt;table cellpadding="0" cellspacing="0" id="z1803e5712c1b4b6791766ce6bf566d51" 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;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/&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;Three Months Ended&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, 2020&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 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;R&amp;amp;D 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;3.9&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%; padding-bottom: 2px;" valign="bottom"&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;SG&amp;amp;A 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;11.4&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/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&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;15.3&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; margin-top: 2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The following table summarizes the severance and retention reserve included in accrued compensation for the period indicated related to Akcea Acquisition (in millions):&lt;/div&gt;

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

&lt;table cellpadding="0" cellspacing="0" id="z320d5d0099aa41cba26e4938ee44b076" 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;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/&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;Three Months Ended&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, 2020&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 88%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Severance &amp;amp; retention reserve beginning balance&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;&#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: top; width: 88%;" valign="bottom"&gt;&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Severance &amp;amp; retention expensed during period&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;15.3&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 88%; 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;Amounts paid during the period&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(0.6&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 88%; padding-bottom: 4px;" valign="bottom"&gt;&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Severance &amp;amp; retention reserve ending balance&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;14.7&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:ConsolidationLessThanWhollyOwnedSubsidiaryParentOwnershipInterestEffectsOfChangesNetTextBlock>
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      id="Fact_632b4ea945604eb682b56b7a5cc7f9af"
      unitRef="U001">3900000</us-gaap:RestructuringCharges>
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      contextRef="c20201001to20201231_IncomeStatementLocationAxis_SellingGeneralAndAdministrativeExpensesMember_RestructuringCostAndReserveAxis_AkceaAcquisitionEmployeeSeveranceAndRetentionMember"
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      unitRef="U001">11400000</us-gaap:RestructuringCharges>
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      unitRef="U001">15300000</us-gaap:RestructuringCharges>
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&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;8. Severance and Retention Costs related to our Restructured European Operations&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;In the fourth quarter of 2020, &lt;/span&gt;we entered into a distribution agreement with Sobi to commercialize TEGSEDI and WAYLIVRA in Europe. Under the distribution agreement, Sobi took over all material distribution operations at the end of January 2021. &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We remain the marketing authorization holder for TEGSEDI and WAYLIVRA in Europe. We will continue to maintain limited European operations including regulatory, manufacturing, and the management of relationships with key opinion leaders. We will also continue to lead the TEGSEDI and WAYLIVRA global commercial strategy.&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 a result of this change, we expect to incur up to $14.8 million of severance and retention expenses. During the fourth quarter of 2020, we recorded $12.5 million of severance and retention related costs in operating expenses related to this agreement. We will recognize the remaining expenses through October 2021, of which we will recognize the majority of the remaining expenses in the first quarter of 2021.&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&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 costs by category related to our restructured European operations (in millions):&lt;/div&gt;

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

&lt;table cellpadding="0" cellspacing="0" id="zfc11f35900ae4dd5aad134392785c1c9" 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;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/&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;Three Months Ended&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, 2020&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 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;R&amp;amp;D 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;4.2&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 88%; padding-bottom: 2px;" valign="bottom"&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;SG&amp;amp;A 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;8.3&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%; 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&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;12.5&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;The following table summarizes the severance and retention reserve included in accrued compensation for the periods indicated related to our restructured European operations (in millions):&lt;/div&gt;

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

&lt;table cellpadding="0" cellspacing="0" id="z4ac59c87d78f4db2a3b3ac5f4b801726" 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;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/&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;Three Months Ended&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, 2020&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 88%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Severance &amp;amp; retention reserve beginning balance&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;&#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: top; width: 88%;" valign="bottom"&gt;&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Severance &amp;amp; retention expensed during period&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;12.5&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;tr&gt;
    &lt;td style="vertical-align: top; width: 88%; 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;Amounts paid during the period&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(0.1&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 88%; padding-bottom: 4px;" valign="bottom"&gt;&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Severance &amp;amp; retention reserve ending balance&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;12.4&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:RestructuringAndRelatedActivitiesDisclosureTextBlock>
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      decimals="-5"
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      unitRef="U001">14800000</us-gaap:RestructuringAndRelatedCostExpectedCost1>
    <us-gaap:RestructuringCharges
      contextRef="c20201001to20201231_RestructuringCostAndReserveAxis_UpdatedEuropeanDistributionModelEmployeeSeveranceAndRetentionMember"
      decimals="-5"
      id="Fact_ac151d77af0549aa963b0bc394117861"
      unitRef="U001">12500000</us-gaap:RestructuringCharges>
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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 costs by category related to our restructured European operations (in millions):&lt;/div&gt;

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

&lt;table cellpadding="0" cellspacing="0" id="zfc11f35900ae4dd5aad134392785c1c9" 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;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/&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;Three Months Ended&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, 2020&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 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;R&amp;amp;D 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;4.2&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 88%; padding-bottom: 2px;" valign="bottom"&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;SG&amp;amp;A 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;8.3&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%; 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&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;12.5&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;The following table summarizes the severance and retention reserve included in accrued compensation for the periods indicated related to our restructured European operations (in millions):&lt;/div&gt;

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

&lt;table cellpadding="0" cellspacing="0" id="z4ac59c87d78f4db2a3b3ac5f4b801726" 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;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/&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;Three Months Ended&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, 2020&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 88%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Severance &amp;amp; retention reserve beginning balance&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;&#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: top; width: 88%;" valign="bottom"&gt;&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Severance &amp;amp; retention expensed during period&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;12.5&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;tr&gt;
    &lt;td style="vertical-align: top; width: 88%; 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;Amounts paid during the period&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(0.1&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 88%; padding-bottom: 4px;" valign="bottom"&gt;&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Severance &amp;amp; retention reserve ending balance&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;12.4&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:ScheduleOfRestructuringAndRelatedCostsTextBlock>
    <us-gaap:RestructuringCharges
      contextRef="c20201001to20201231_IncomeStatementLocationAxis_ResearchAndDevelopmentExpensesMember_RestructuringCostAndReserveAxis_UpdatedEuropeanDistributionModelEmployeeSeveranceAndRetentionMember"
      decimals="-5"
      id="Fact_4e2370f605984a7aa1aa424b6750b018"
      unitRef="U001">4200000</us-gaap:RestructuringCharges>
    <us-gaap:RestructuringCharges
      contextRef="c20201001to20201231_IncomeStatementLocationAxis_SellingGeneralAndAdministrativeExpensesMember_RestructuringCostAndReserveAxis_UpdatedEuropeanDistributionModelEmployeeSeveranceAndRetentionMember"
      decimals="-5"
      id="Fact_daae0140842f4814ac2e22656697ecab"
      unitRef="U001">8300000</us-gaap:RestructuringCharges>
    <us-gaap:RestructuringCharges
      contextRef="c20201001to20201231_RestructuringCostAndReserveAxis_UpdatedEuropeanDistributionModelEmployeeSeveranceAndRetentionMember"
      decimals="-5"
      id="Fact_6015c168dba040d5ab6a9c0c2eae3f46"
      unitRef="U001">12500000</us-gaap:RestructuringCharges>
    <us-gaap:RestructuringReserve
      contextRef="c20200930_RestructuringCostAndReserveAxis_UpdatedEuropeanDistributionModelEmployeeSeveranceAndRetentionMember"
      decimals="-6"
      id="Fact_d10ad7f8d44642e99183b49ca854d30b"
      unitRef="U001">0</us-gaap:RestructuringReserve>
    <us-gaap:RestructuringCharges
      contextRef="c20201001to20201231_RestructuringCostAndReserveAxis_UpdatedEuropeanDistributionModelEmployeeSeveranceAndRetentionMember"
      decimals="-5"
      id="Fact_523f6a352a20442397b200bb597b61b1"
      unitRef="U001">12500000</us-gaap:RestructuringCharges>
    <us-gaap:PaymentsForRestructuring
      contextRef="c20201001to20201231_RestructuringCostAndReserveAxis_UpdatedEuropeanDistributionModelEmployeeSeveranceAndRetentionMember"
      decimals="-5"
      id="Fact_a44203769d1b4ce790019f99f595bdfa"
      unitRef="U001">100000</us-gaap:PaymentsForRestructuring>
    <us-gaap:RestructuringReserve
      contextRef="c20201231_BalanceSheetLocationAxis_EmployeeRelatedLiabilitiesCurrentMember_RestructuringCostAndReserveAxis_UpdatedEuropeanDistributionModelEmployeeSeveranceAndRetentionMember"
      decimals="-5"
      id="Fact_b1d0d25b082e45e1be9c08edc1275b31"
      unitRef="U001">12400000</us-gaap:RestructuringReserve>
    <us-gaap:SegmentReportingDisclosureTextBlock
      contextRef="c20200101to20201231"
      id="Text_2b6a002acca646b0906b3570ab8ac869">
&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;9. Segment Information and Concentration of Business 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;Through 2020, we had two reportable segments, our Ionis Core segment and Akcea Therapeutics. &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We have provided segment financial information and results for our Ionis Core segment and our Akcea Therapeutics segment based on the segregation of revenues and expenses that our chief decision maker reviewed to assess operating performance and to make operating decisions through 2020.&lt;/span&gt; Segment income (loss) from operations includes revenue less operating expenses attributable to each segment.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&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 Ionis Core segment, we are exploiting our antisense technology to generate a broad pipeline of first-in-class and/or best-in-class medicines for us and our partners. Our Ionis Core segment generates revenue from a multifaceted partnering strategy.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&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;Akcea was&lt;/span&gt; focused on developing and commercializing medicines to treat patients with serious and rare diseases&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;. Akcea generated revenue from TEGSEDI and WAYLIVRA product sales and from its collaborations.&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 tables show our segment revenue and income (loss) from operations for &lt;/span&gt;2020, 2019 and 2018&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; (in thousands), respectively.&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" id="zef53d7fefabb427795be91924081cd7f" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; border-bottom: #000000 2px solid; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2020&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Ionis Core&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; 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;Akcea Therapeutics&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; 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;Elimination of&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Intercompany Activity&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; 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;Total&lt;/div&gt;&lt;/td&gt;
    &lt;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; white-space: nowrap;" 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; 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; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; 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; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; 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; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; 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; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; margin-left: 7.2pt; 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; 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; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; 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; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; 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; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; 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; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 52%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; margin-left: 25.2pt; 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; 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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;286,583&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;&#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; 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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;286,583&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; 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: 52%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; margin-left: 25.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Product sales, net&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;&#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%; 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;69,999&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: 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;&#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%; 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;69,999&lt;/div&gt;&lt;/td&gt;
    &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: 52%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; margin-left: 25.2pt; 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; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;11,334&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(3,217&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;8,117&lt;/div&gt;&lt;/td&gt;
    &lt;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: top; width: 52%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; margin-left: 43.2pt; 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%; 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;297,917&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;69,999&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;(3,217&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;364,699&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: top; width: 52%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; margin-left: 7.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;R&amp;amp;D revenue under collaborative agreements&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;325,024&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;82,321&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(42,780&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;364,565&lt;/div&gt;&lt;/td&gt;
    &lt;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: top; width: 52%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; margin-left: 25.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total segment revenue&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;622,941&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;152,320&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(45,997&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;729,264&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;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 52%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total operating expenses&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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;563,647&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;389,575&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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(51,876&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;901,346&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 52%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Income (loss) from operations&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;59,294&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(237,255&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;5,879&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(172,082&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&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" id="zd5bde97ab66c4903be53b04e577e42d6" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; border-bottom: #000000 2px solid; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2019&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Ionis Core&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; 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;Akcea Therapeutics&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; 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;Elimination of&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Intercompany Activity&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; 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;Total&lt;/div&gt;&lt;/td&gt;
    &lt;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; white-space: nowrap;" 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; 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; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; 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; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; 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; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; 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; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; margin-left: 7.2pt; 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; 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; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; 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; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; 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; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; 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; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 52%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; margin-left: 25.2pt; 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; 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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;292,992&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;&#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; 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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;292,992&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; 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: 52%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; margin-left: 25.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Product sales, net&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;&#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%; 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;42,253&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: 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;&#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%; 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;42,253&lt;/div&gt;&lt;/td&gt;
    &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: 52%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; margin-left: 25.2pt; 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; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;12,616&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;10,172&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(5,583&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;17,205&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 52%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; margin-left: 43.2pt; 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%; 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;305,608&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;52,425&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;(5,583&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;352,450&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 52%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; margin-left: 7.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;R&amp;amp;D revenue under collaborative agreements&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;553,038&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;436,118&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(219,007&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;770,149&lt;/div&gt;&lt;/td&gt;
    &lt;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: top; width: 52%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; margin-left: 25.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total segment revenue&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;858,646&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;488,543&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(224,590&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,122,599&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;tr&gt;
    &lt;td style="vertical-align: top; width: 52%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total operating expenses&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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;523,207&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;450,469&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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(216,960&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;756,716&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 52%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Income (loss) from operations&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;335,439&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;38,074&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(7,630&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;365,883&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" id="zfeba46abdf4c46b192c4196f9b159018" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; border-bottom: #000000 2px solid; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2018&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Ionis Core&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; 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;Akcea Therapeutics&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; 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;Elimination of&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Intercompany Activity&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; 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;Total&lt;/div&gt;&lt;/td&gt;
    &lt;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; white-space: nowrap;" 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; 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; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; 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; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; 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; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; 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; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; margin-left: 7.2pt; 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; 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; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; 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; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; 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; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; 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; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 52%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; margin-left: 25.2pt; 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; 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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;237,930&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;&#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; 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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;237,930&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; 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: 52%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; margin-left: 25.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Product sales, net&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;&#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%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2,237&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: 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;&#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%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2,237&lt;/div&gt;&lt;/td&gt;
    &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: 52%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; margin-left: 25.2pt; 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; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2,755&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;12,000&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;14,755&lt;/div&gt;&lt;/td&gt;
    &lt;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: top; width: 52%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; margin-left: 43.2pt; 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%; 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;240,685&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;14,237&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;&#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; 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;254,922&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 52%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; margin-left: 7.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;R&amp;amp;D revenue under collaborative agreements&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;401,259&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;50,630&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(107,137&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;344,752&lt;/div&gt;&lt;/td&gt;
    &lt;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: top; width: 52%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; margin-left: 25.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total segment revenue&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;641,944&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;64,867&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(107,137&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;599,674&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;tr&gt;
    &lt;td style="vertical-align: top; width: 52%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total operating expenses&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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;380,212&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;295,683&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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(14,849&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;661,046&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 52%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Income (loss) from operations&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;261,732&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(230,816&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(92,288&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(61,372&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&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&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 shows our total assets by segment at December 31, 2020 and 2019 (in thousands), respectively.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" id="z700a3f8134a24e26a84152eb605d3867" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; border-bottom: #000000 2px solid; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Total Assets&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Ionis Core&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; 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;Akcea Therapeutics&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; 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;Elimination of&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Intercompany Activity&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; 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;Total&lt;/div&gt;&lt;/td&gt;
    &lt;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: 52%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;December 31, 2020&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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2,792,222&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;435,824&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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(838,291&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;2,389,755&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 52%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;December 31, 2019&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;3,478,081&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;599,250&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(844,219&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;3,233,112&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;/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;Contracts receivables at December 31, 2020 was comprised of approximately 99.5percent from two significant partners. Contracts receivables at December 31, 2019 was comprised of approximately 75 percent from one significant partner.&lt;/div&gt;
</us-gaap:SegmentReportingDisclosureTextBlock>
    <us-gaap:NumberOfReportableSegments
      contextRef="c20200101to20201231"
      decimals="INF"
      id="Fact_7b6216c3ebc44b518de52c3d575b97de"
      unitRef="U009">2</us-gaap:NumberOfReportableSegments>
    <us-gaap:ScheduleOfSegmentReportingInformationBySegmentTextBlock
      contextRef="c20200101to20201231"
      id="Text_cdea546702a94035a18d47f0db0f4848">
&lt;div style="display:none;"&gt;&lt;br/&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 tables show our segment revenue and income (loss) from operations for &lt;/span&gt;2020, 2019 and 2018&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; (in thousands), respectively.&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" id="zef53d7fefabb427795be91924081cd7f" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; border-bottom: #000000 2px solid; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2020&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Ionis Core&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; 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;Akcea Therapeutics&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; 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;Elimination of&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Intercompany Activity&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; 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;Total&lt;/div&gt;&lt;/td&gt;
    &lt;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; white-space: nowrap;" 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; 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; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; 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; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; 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; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; 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; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; margin-left: 7.2pt; 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; 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; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; 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; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; 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; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; 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; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 52%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; margin-left: 25.2pt; 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; 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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;286,583&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;&#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; 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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;286,583&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; 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: 52%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; margin-left: 25.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Product sales, net&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;&#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%; 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;69,999&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: 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;&#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%; 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;69,999&lt;/div&gt;&lt;/td&gt;
    &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: 52%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; margin-left: 25.2pt; 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; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;11,334&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(3,217&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;8,117&lt;/div&gt;&lt;/td&gt;
    &lt;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: top; width: 52%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; margin-left: 43.2pt; 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%; 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;297,917&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;69,999&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;(3,217&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;364,699&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: top; width: 52%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; margin-left: 7.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;R&amp;amp;D revenue under collaborative agreements&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;325,024&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;82,321&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(42,780&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;364,565&lt;/div&gt;&lt;/td&gt;
    &lt;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: top; width: 52%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; margin-left: 25.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total segment revenue&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;622,941&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;152,320&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(45,997&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;729,264&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;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 52%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total operating expenses&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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;563,647&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;389,575&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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(51,876&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;901,346&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 52%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Income (loss) from operations&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;59,294&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(237,255&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;5,879&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(172,082&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&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" id="zd5bde97ab66c4903be53b04e577e42d6" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; border-bottom: #000000 2px solid; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2019&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Ionis Core&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; 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;Akcea Therapeutics&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; 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;Elimination of&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Intercompany Activity&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; 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;Total&lt;/div&gt;&lt;/td&gt;
    &lt;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; white-space: nowrap;" 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; 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; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; 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; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; 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; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; 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; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; margin-left: 7.2pt; 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; 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; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; 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; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; 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; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; 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; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 52%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; margin-left: 25.2pt; 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; 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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;292,992&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;&#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; 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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;292,992&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; 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: 52%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; margin-left: 25.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Product sales, net&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;&#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%; 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;42,253&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: 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;&#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%; 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;42,253&lt;/div&gt;&lt;/td&gt;
    &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: 52%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; margin-left: 25.2pt; 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; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;12,616&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;10,172&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(5,583&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;17,205&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 52%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; margin-left: 43.2pt; 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%; 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;305,608&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;52,425&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;(5,583&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;352,450&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 52%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; margin-left: 7.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;R&amp;amp;D revenue under collaborative agreements&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;553,038&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;436,118&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(219,007&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;770,149&lt;/div&gt;&lt;/td&gt;
    &lt;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: top; width: 52%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; margin-left: 25.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total segment revenue&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;858,646&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;488,543&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(224,590&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,122,599&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;tr&gt;
    &lt;td style="vertical-align: top; width: 52%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total operating expenses&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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;523,207&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;450,469&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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(216,960&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;756,716&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 52%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Income (loss) from operations&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;335,439&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;38,074&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(7,630&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;365,883&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" id="zfeba46abdf4c46b192c4196f9b159018" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; border-bottom: #000000 2px solid; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2018&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Ionis Core&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; 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;Akcea Therapeutics&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; 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;Elimination of&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Intercompany Activity&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; 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;Total&lt;/div&gt;&lt;/td&gt;
    &lt;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; white-space: nowrap;" 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; 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; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; 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; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; 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; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; 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; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; margin-left: 7.2pt; 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; 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; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; 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; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; 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; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; 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; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 52%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; margin-left: 25.2pt; 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; 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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;237,930&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;&#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; 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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;237,930&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; 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: 52%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; margin-left: 25.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Product sales, net&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;&#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%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2,237&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: 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;&#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%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2,237&lt;/div&gt;&lt;/td&gt;
    &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: 52%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; margin-left: 25.2pt; 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; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2,755&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;12,000&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;14,755&lt;/div&gt;&lt;/td&gt;
    &lt;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: top; width: 52%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; margin-left: 43.2pt; 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%; 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;240,685&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;14,237&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;&#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; 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;254,922&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 52%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; margin-left: 7.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;R&amp;amp;D revenue under collaborative agreements&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;401,259&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;50,630&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(107,137&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;344,752&lt;/div&gt;&lt;/td&gt;
    &lt;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: top; width: 52%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; margin-left: 25.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total segment revenue&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;641,944&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;64,867&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(107,137&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;599,674&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;tr&gt;
    &lt;td style="vertical-align: top; width: 52%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total operating expenses&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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;380,212&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;295,683&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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(14,849&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;661,046&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 52%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Income (loss) from operations&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;261,732&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(230,816&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(92,288&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(61,372&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&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&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 shows our total assets by segment at December 31, 2020 and 2019 (in thousands), respectively.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" id="z700a3f8134a24e26a84152eb605d3867" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; border-bottom: #000000 2px solid; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Total Assets&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Ionis Core&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; 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;Akcea Therapeutics&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; 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;Elimination of&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Intercompany Activity&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; 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;Total&lt;/div&gt;&lt;/td&gt;
    &lt;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: 52%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;December 31, 2020&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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2,792,222&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;435,824&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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(838,291&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;2,389,755&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 52%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;December 31, 2019&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;3,478,081&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;599,250&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(844,219&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;3,233,112&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;/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;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 $19,500 and $26,000 in 2020 for employees under 50 years old and employees 50 years old or over, respectively. We made approximately $5.7 million, $6.4 million and $5.7 million in matching contributions for the years ended December 31, 2020, 2019 and 2018, respectively.&lt;/div&gt;
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      unitRef="U001">19500</us-gaap:DefinedContributionPlanMaximumAnnualContributionsPerEmployeeAmount>
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    <us-gaap:DefinedContributionPlanCostRecognized
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    <us-gaap:LegalMattersAndContingenciesTextBlock
      contextRef="c20200101to20201231"
      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 the potential loss from any legal proceeding is considered probable and the amount can be reasonably estimated, we accrue a liability for the estimated loss. Significant judgment is required to determine the probability of a loss and whether the amount of the loss is reasonably estimable. The outcome of any proceeding is not determinable in advance. As a result, the assessment of a potential liability and the amount of accruals recorded are based only on the information available to us at the time. As additional information becomes available, we reassess the potential liability related to the legal proceeding, and may revise our estimates.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;On July 16, 2020, a purported stockholder of Akcea filed an action in the Delaware Court of Chancery captioned John Makris, et al. v. Stanley T. Crooke, et al., C.A. No. 2020-0587, or the &#x201c;Delaware Action.&#x201d; The plaintiff in the Delaware Action asserts claims against (i) current and former members of Akcea&#x2019;s board of directors; and (ii) Ionis, or collectively, the &#x201c;Defendants&#x201d;. The plaintiff asserts derivative claims on behalf of Akcea, which is a nominal defendant in the Delaware Action, as well as putatively direct claims on behalf of a purported class of Akcea&#x2019;s stockholders. The plaintiff in the Delaware action asserts that the Defendants breached their fiduciary duties in connection with the licensing transaction that we and Akcea entered into regarding TEGSEDI and IONIS-TTR-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;. The plaintiff also asserts an unjust enrichment claim against Ionis. The plaintiff&#x2019;s claims are similar to those asserted in a prior action in the Delaware Court of Chancery captioned City of Cambridge Retirement System v. Crooke, et al., C.A. No. 2019-0905, which was dismissed with prejudice to the named plaintiff only on April 8, 2020. We believe that the claims asserted in the Delaware Action are without merit and anticipate filing a motion to dismiss the claims.&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;In light of the August 31, 2020 public announcement of the Akcea Acquisition, the parties to the Delaware Action entered into a stipulation whereby the Defendants need to respond to the complaint filed on July 16, 2020, and the plaintiff will file an amended complaint. The amended complaint has not yet been filed.&lt;/span&gt;&lt;/div&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;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 2020 and 2019 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" id="zb2695825d71444f0828c50eac6305221" 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;2020&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2019&lt;/div&gt;&lt;/td&gt;
    &lt;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&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;290,281&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;493,680&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #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&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;312,945&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;233,028&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Income (loss) from operations&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(22,664&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;260,652&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 76%;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Net income (loss)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(341,426&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;203,957&lt;/div&gt;&lt;/td&gt;
    &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;Net income (loss) attributable to Ionis Pharmaceuticals, Inc. common stockholders&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(340,271&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;184,415&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #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;Basic net income (loss) per share (1) (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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(2.44&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;1.31&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;&#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;Diluted net income (loss) per share (1) (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;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(2.44&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1.28&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-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: 10pt;"&gt;________________&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z95fc0fe83dcc44d3beffd99343c41418" 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; vertical-align: top; align: right; 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: left;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We &lt;/span&gt;compute net income (loss) per share independently for each quarter during &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;the year.&lt;/span&gt;&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z7f159b28bab545f4b7ef06cc58aafa2d" 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; vertical-align: top; align: right; 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;As discussed in Note 1, &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Organization and Significant Accounting Policies, &lt;/span&gt;we compute basic net income (loss) per share by dividing the total net income (loss) attributable to our common stockholders by our weighted-average number of common shares outstanding during the period. Our basic net income (loss) per share calculation for each of the fourth quarters in 2020 and 2019 considered our net income (loss) for Ionis on a stand-alone basis plus our share of Akcea&#x2019;s net loss for the period. To calculate the portion of Akcea&#x2019;s net loss attributable to our ownership, we multiplied Akcea&#x2019;s loss per share by the weighted average shares we owned in Akcea during the period. As a result of this calculation, our total net income (loss) available to Ionis common stockholders for the calculation of net income (loss) per share is different than net income (loss) attributable to Ionis Pharmaceuticals, Inc. common stockholders in the consolidated statements of operations.&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="text-align: justify; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Our basic net income (loss) per share the quarter referenced was calculated as follows (in thousands, except per share amounts):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" id="z575ab3fcea8448b08361487272ec926a" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; border-bottom: #000000 2px solid; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Three Months Ended December 31 , 2020&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Weighted&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Average Shares&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Owned in Akcea&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Akcea&lt;/span&gt;&#x2019;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;s&lt;/span&gt;&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Net Loss&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Per Share&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Basic Net Loss&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Per Share&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Calculation&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Akcea&#x2019;s net loss in the pre-acquisition period attributable to our ownership&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;77,095&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(0.05&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;(3,603&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Akcea&#x2019;s net loss in the post-acquisition period attributable to our ownership&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(85,987&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Akcea&#x2019;s total net loss attributable to our ownership&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(89,590&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Ionis&#x2019; stand-alone net loss&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(250,682&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Net loss available to Ionis common stockholders&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(340,272&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Weighted average shares outstanding&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;139,956&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Basic net loss per share&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(2.44&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&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" id="z4d63d8880724435496c59a8fec3d2f7e" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; border-bottom: #000000 2px solid; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Three Months Ended December 31 , 2019&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Weighted&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Average Shares&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Owned in Akcea&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Akcea&lt;/span&gt;&#x2019;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;s&lt;/span&gt;&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Net Income&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Per Share&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Basic Net Income&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Per Share&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Calculation&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Common shares&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;71,342&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.87&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;62,243&lt;/div&gt;&lt;/td&gt;
    &lt;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: top; width: 64%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Akcea&#x2019;s net income attributable to our ownership&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;&#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%; 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;&#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%; 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;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&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;62,243&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Ionis&#x2019; stand-alone net income&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;121,552&lt;/div&gt;&lt;/td&gt;
    &lt;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: top; width: 64%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Net income available to Ionis common stockholders&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 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; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;183,795&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Weighted average shares outstanding&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;140,583&lt;/div&gt;&lt;/td&gt;
    &lt;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: top; width: 64%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Basic net income per share&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1.31&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z24e5fa74899b4127901c49f6468fa415" 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; vertical-align: top; align: right; 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;We had net income available to Ionis common stockholders for the fourth quarter of 2019. As a result, we computed diluted net income per share using the weighted-average number of common shares and dilutive common equivalent shares outstanding during the period as follows (in thousands except per share amounts):&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" id="zfe4ce006369c42c0ae6332b5d889d237" 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, 2019&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Income&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;(Numerator)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Shares&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;(Denominator)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Per-Share&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Amount&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Net income available to Ionis common stockholders&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;183,795&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;140,583&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;1.31&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Effect of dilutive securities:&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 21pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Shares issuable upon exercise of stock options&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,467&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 21pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Shares issuable upon restricted stock award issuance&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;848&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 21pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Shares issuable related to our ESPP&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;18&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 21pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Shares issuable related to our 0.125 percent convertible notes&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;644&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: 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;860&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 21pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Shares issuable related to our 1 percent convertible notes&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;12,046&lt;/div&gt;&lt;/td&gt;
    &lt;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;9,527&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #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;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 4px;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Income available to Ionis common stockholders, plus assumed conversions&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" 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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;196,485&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;153,303&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;1.28&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:QuarterlyFinancialInformationTextBlock>
    <us-gaap:ScheduleOfQuarterlyFinancialInformationTableTextBlock
      contextRef="c20200101to20201231"
      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 2020 and 2019 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" id="zb2695825d71444f0828c50eac6305221" 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;2020&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2019&lt;/div&gt;&lt;/td&gt;
    &lt;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&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;290,281&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;493,680&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #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&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;312,945&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;233,028&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Income (loss) from operations&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(22,664&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;260,652&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 76%;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Net income (loss)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(341,426&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;203,957&lt;/div&gt;&lt;/td&gt;
    &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;Net income (loss) attributable to Ionis Pharmaceuticals, Inc. common stockholders&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(340,271&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;184,415&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #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;Basic net income (loss) per share (1) (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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(2.44&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;1.31&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;&#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;Diluted net income (loss) per share (1) (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;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(2.44&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1.28&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-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: 10pt;"&gt;________________&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z95fc0fe83dcc44d3beffd99343c41418" 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; vertical-align: top; align: right; 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: left;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We &lt;/span&gt;compute net income (loss) per share independently for each quarter during &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;the year.&lt;/span&gt;&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z7f159b28bab545f4b7ef06cc58aafa2d" 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; vertical-align: top; align: right; 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;As discussed in Note 1, &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Organization and Significant Accounting Policies, &lt;/span&gt;we compute basic net income (loss) per share by dividing the total net income (loss) attributable to our common stockholders by our weighted-average number of common shares outstanding during the period. Our basic net income (loss) per share calculation for each of the fourth quarters in 2020 and 2019 considered our net income (loss) for Ionis on a stand-alone basis plus our share of Akcea&#x2019;s net loss for the period. To calculate the portion of Akcea&#x2019;s net loss attributable to our ownership, we multiplied Akcea&#x2019;s loss per share by the weighted average shares we owned in Akcea during the period. As a result of this calculation, our total net income (loss) available to Ionis common stockholders for the calculation of net income (loss) per share is different than net income (loss) attributable to Ionis Pharmaceuticals, Inc. common stockholders in the consolidated statements of operations.&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="text-align: justify; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Our basic net income (loss) per share the quarter referenced was calculated as follows (in thousands, except per share amounts):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" id="z575ab3fcea8448b08361487272ec926a" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; border-bottom: #000000 2px solid; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Three Months Ended December 31 , 2020&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Weighted&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Average Shares&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Owned in Akcea&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Akcea&lt;/span&gt;&#x2019;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;s&lt;/span&gt;&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Net Loss&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Per Share&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Basic Net Loss&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Per Share&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Calculation&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Akcea&#x2019;s net loss in the pre-acquisition period attributable to our ownership&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;77,095&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(0.05&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;(3,603&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Akcea&#x2019;s net loss in the post-acquisition period attributable to our ownership&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(85,987&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Akcea&#x2019;s total net loss attributable to our ownership&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(89,590&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Ionis&#x2019; stand-alone net loss&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(250,682&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Net loss available to Ionis common stockholders&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(340,272&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Weighted average shares outstanding&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;139,956&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Basic net loss per share&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(2.44&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&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" id="z4d63d8880724435496c59a8fec3d2f7e" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; border-bottom: #000000 2px solid; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Three Months Ended December 31 , 2019&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Weighted&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Average Shares&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Owned in Akcea&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Akcea&lt;/span&gt;&#x2019;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;s&lt;/span&gt;&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Net Income&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Per Share&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Basic Net Income&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Per Share&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Calculation&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Common shares&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;71,342&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.87&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;62,243&lt;/div&gt;&lt;/td&gt;
    &lt;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: top; width: 64%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Akcea&#x2019;s net income attributable to our ownership&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;&#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%; 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;&#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%; 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;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&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;62,243&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Ionis&#x2019; stand-alone net income&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;121,552&lt;/div&gt;&lt;/td&gt;
    &lt;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: top; width: 64%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Net income available to Ionis common stockholders&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 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; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;183,795&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Weighted average shares outstanding&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;140,583&lt;/div&gt;&lt;/td&gt;
    &lt;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: top; width: 64%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Basic net income per share&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1.31&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z24e5fa74899b4127901c49f6468fa415" 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; vertical-align: top; align: right; 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;We had net income available to Ionis common stockholders for the fourth quarter of 2019. As a result, we computed diluted net income per share using the weighted-average number of common shares and dilutive common equivalent shares outstanding during the period as follows (in thousands except per share amounts):&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" id="zfe4ce006369c42c0ae6332b5d889d237" 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, 2019&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Income&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;(Numerator)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Shares&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;(Denominator)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Per-Share&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Amount&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Net income available to Ionis common stockholders&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;183,795&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;140,583&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;1.31&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Effect of dilutive securities:&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 21pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Shares issuable upon exercise of stock options&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,467&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 21pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Shares issuable upon restricted stock award issuance&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;848&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 21pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Shares issuable related to our ESPP&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;18&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 21pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Shares issuable related to our 0.125 percent convertible notes&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;644&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: 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;860&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 21pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Shares issuable related to our 1 percent convertible notes&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;12,046&lt;/div&gt;&lt;/td&gt;
    &lt;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;9,527&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #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;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 4px;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Income available to Ionis common stockholders, plus assumed conversions&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" 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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;196,485&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;153,303&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;1.28&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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        <link:footnote id="Foot_77eb85d4142a44a68a7c6b25a7169d1c" xlink:label="Foot_77eb85d4142a44a68a7c6b25a7169d1c" xlink:role="http://www.xbrl.org/2003/role/footnote" xlink:type="resource" xml:lang="en-US">$10.0 million included in cash and cash equivalents on our consolidated balance sheet, with the difference included in short-term investments on our consolidated balance sheet.</link:footnote>
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        <link:footnote id="Foot_9a970986ba874d05b3ae45569fb070a7" xlink:label="Foot_9a970986ba874d05b3ae45569fb070a7" xlink:role="http://www.xbrl.org/2003/role/footnote" xlink:type="resource" xml:lang="en-US">We classified the carrying value of our 1% Notes as a current liability on our consolidated balance sheet at December 31, 2020 because it matures in November 2021.</link:footnote>
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        <link:footnote id="Foot_94c9e35c930540ad8f4b6bdd98cbf740" xlink:label="Foot_94c9e35c930540ad8f4b6bdd98cbf740" xlink:role="http://www.xbrl.org/2003/role/footnote" xlink:type="resource" xml:lang="en-US">For our 1% Notes, our effective interest rate represents our effective interest rate after our December 2019 debt exchange.</link:footnote>
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        <link:footnote id="Foot_92f3ab0ee45a44b9baf44a6e4c6792b4" xlink:label="Foot_92f3ab0ee45a44b9baf44a6e4c6792b4" xlink:role="http://www.xbrl.org/2003/role/footnote" xlink:type="resource" xml:lang="en-US">Our equity securities included in deposits and other assets consisted of our investments in privately held companies. We recognize our private company equity securities at 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 on our consolidated balance sheet.</link:footnote>
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        <link:footnote id="Foot_c498c367d1f949d4a789172bf48c4121" xlink:label="Foot_c498c367d1f949d4a789172bf48c4121" xlink:role="http://www.xbrl.org/2003/role/footnote" xlink:type="resource" xml:lang="en-US">Included in other current assets on our consolidated balance sheet.</link:footnote>
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        <link:footnote id="Foot_e2e8d94790c647a9a64e7b8a949e611c" xlink:label="Foot_e2e8d94790c647a9a64e7b8a949e611c" xlink:role="http://www.xbrl.org/2003/role/footnote" xlink:type="resource" xml:lang="en-US">Current portion of $2.0 million was included in <xhtml:span style="-sec-ix-hidden:Fact_530181678e9244af8b37885d3ba85980">current portion of long-term obligations</xhtml:span> on our consolidated balance sheet, with the difference included in <xhtml:span style="-sec-ix-hidden:Fact_9c37cb3853f74a4f821bbe4ed37a06ba">long-term obligations</xhtml:span>.</link:footnote>
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<head>
<title></title>
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<span style="display: none;">v3.20.4</span><table class="report" border="0" cellspacing="2" id="idm140142740709864">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Document and Entity Information - USD ($)<br></strong></div></th>
<th class="th" colspan="1">12 Months Ended</th>
<th class="th" colspan="1"></th>
<th class="th" colspan="1"></th>
</tr>
<tr>
<th class="th"><div>Dec. 31, 2020</div></th>
<th class="th"><div>Feb. 18, 2021</div></th>
<th class="th"><div>Jun. 30, 2020</div></th>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_dei_CoverAbstract', window );"><strong>Cover [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_dei_EntityRegistrantName', window );">Entity Registrant Name</a></td>
<td class="text">Ionis Pharmaceuticals, Inc<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_dei_EntityCentralIndexKey', window );">Entity Central Index Key</a></td>
<td class="text">0000874015<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_dei_CurrentFiscalYearEndDate', window );">Current Fiscal Year End Date</a></td>
<td class="text">--12-31<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_dei_DocumentType', window );">Document Type</a></td>
<td class="text">10-K<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_dei_AmendmentFlag', window );">Amendment Flag</a></td>
<td class="text">false<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
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<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_dei_DocumentAnnualReport', window );">Document Annual Report</a></td>
<td class="text">true<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_dei_DocumentPeriodEndDate', window );">Document Period End Date</a></td>
<td class="text">Dec. 31,  2020<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_dei_DocumentFiscalYearFocus', window );">Document Fiscal Year Focus</a></td>
<td class="text">2020<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="top.Show.showAR( this, 'defref_dei_DocumentFiscalPeriodFocus', window );">Document Fiscal Period Focus</a></td>
<td class="text">FY<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
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<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_dei_DocumentTransitionReport', window );">Document Transition Report</a></td>
<td class="text">false<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 class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_dei_EntityFileNumber', window );">Entity File Number</a></td>
<td class="text">000-19125<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_dei_EntityIncorporationStateCountryCode', window );">Entity Incorporation, State or Country Code</a></td>
<td class="text">DE<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_dei_EntityTaxIdentificationNumber', window );">Entity Tax Identification Number</a></td>
<td class="text">33-0336973<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
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<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_dei_EntityAddressAddressLine1', window );">Entity Address, Address Line One</a></td>
<td class="text">2855 Gazelle Court<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
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<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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>
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<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="top.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="top.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="top.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="top.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="top.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="top.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="top.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="top.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>
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<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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>
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<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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>
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<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="top.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="top.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="top.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="top.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">$ 6,748,320,336<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_dei_EntityCommonStockSharesOutstanding', window );">Entity Common Stock, Shares Outstanding</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">140,862,211<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
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<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_AmendmentFlag">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ 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>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
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<td><strong> Data Type:</strong></td>
<td>xbrli:booleanItemType</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>
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<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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Area code of city</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ 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>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
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<td><strong> Data Type:</strong></td>
<td>xbrli:normalizedStringItemType</td>
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<td><strong> Balance Type:</strong></td>
<td>na</td>
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<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
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</div></td></tr>
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<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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Cover page.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ 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>
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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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<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_dei_CurrentFiscalYearEndDate">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ 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>
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<td><strong> Data Type:</strong></td>
<td>xbrli:gMonthDayItemType</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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</table></div>
</div></td></tr>
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<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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.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, 20-F, 40-F<br> -Number 240<br> -Section 15<br> -Subsection d-1<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ 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>
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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:booleanItemType</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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</div></td></tr>
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<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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ 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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>This is focus fiscal year of the document report in CCYY 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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ 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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The end date of the period reflected on the cover page if a periodic report. For all other reports and registration statements containing historical data, it is the date up through which that historical data is presented.  If there is no historical data in the report, use the filing date. The format of the date is CCYY-MM-DD.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ 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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.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="top.Show.toggleNext( this );">+ 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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ 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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ 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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Name of the City or Town</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ 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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Code for the postal or zip code</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ 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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Name of the state or province.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ 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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.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 12B<br> -Number 240<br> -Section 12<br> -Subsection b-2<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ 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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ 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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ 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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Indicate if registrant meets the emerging growth company criteria.</p></div>
<a href="javascript:void(0);" onclick="top.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 12B<br> -Number 240<br> -Section 12<br> -Subsection b-2<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ 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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ 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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.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 12B<br> -Number 240<br> -Section 12<br> -Subsection b-2<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ 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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ 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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.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="top.Show.toggleNext( this );">+ 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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ 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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.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 12B<br> -Number 240<br> -Section 12<br> -Subsection b-2<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ 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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.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 12B<br> -Number 240<br> -Section 12<br> -Subsection b-2<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ 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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.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 12B<br> -Number 240<br> -Section 12<br> -Subsection b-2<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ 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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.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 12B<br> -Number 240<br> -Section 12<br> -Subsection b-2<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ 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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ 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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ 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_LocalPhoneNumber">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Local phone number for entity.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ 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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Title of a 12(b) registered security.</p></div>
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ 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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.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="top.Show.toggleNext( this );">+ 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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_TradingSymbol</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dei:tradingSymbolItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
</div>
</body>
</html>
</TEXT>
</DOCUMENT>
<DOCUMENT>
<TYPE>XML
<SEQUENCE>38
<FILENAME>R2.htm
<DESCRIPTION>IDEA: XBRL DOCUMENT
<TEXT>
<html>
<head>
<title></title>
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<span style="display: none;">v3.20.4</span><table class="report" border="0" cellspacing="2" id="idm140142741048280">
<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, 2020</div></th>
<th class="th"><div>Dec. 31, 2019</div></th>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="top.Show.showAR( this, 'defref_us-gaap_CashAndCashEquivalentsAtCarryingValue', window );">Cash and cash equivalents</a></td>
<td class="nump">$ 397,664<span></span>
</td>
<td class="nump">$ 683,287<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesDebtSecuritiesCurrent', window );">Short-term investments</a></td>
<td class="nump">1,494,711<span></span>
</td>
<td class="nump">1,816,257<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ContractWithCustomerAssetNetCurrent', window );">Contracts receivable</a></td>
<td class="nump">76,204<span></span>
</td>
<td class="nump">63,034<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_InventoryNet', window );">Inventories</a></td>
<td class="nump">21,965<span></span>
</td>
<td class="nump">18,180<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_OtherAssetsCurrent', window );">Other current assets</a></td>
<td class="nump">140,163<span></span>
</td>
<td class="nump">139,839<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AssetsCurrent', window );">Total current assets</a></td>
<td class="nump">2,130,707<span></span>
</td>
<td class="nump">2,720,597<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentNet', window );">Property, plant and equipment, net</a></td>
<td class="nump">181,077<span></span>
</td>
<td class="nump">153,651<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_FiniteLivedIntangibleAssetsNet', window );">Patents, net</a></td>
<td class="nump">27,937<span></span>
</td>
<td class="nump">25,674<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_DeferredIncomeTaxAssetsNet', window );">Long-term deferred tax assets</a></td>
<td class="nump">0<span></span>
</td>
<td class="nump">305,557<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_OtherAssetsNoncurrent', window );">Deposits and other assets</a></td>
<td class="nump">50,034<span></span>
</td>
<td class="nump">27,633<span></span>
</td>
</tr>
<tr class="rou">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_Assets', window );">Total assets</a></td>
<td class="nump">2,389,755<span></span>
</td>
<td class="nump">3,233,112<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="top.Show.showAR( this, 'defref_us-gaap_AccountsPayableCurrent', window );">Accounts payable</a></td>
<td class="nump">17,199<span></span>
</td>
<td class="nump">16,067<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_EmployeeRelatedLiabilitiesCurrent', window );">Accrued compensation</a></td>
<td class="nump">65,728<span></span>
</td>
<td class="nump">37,357<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AccruedLiabilitiesCurrent', window );">Accrued liabilities</a></td>
<td class="nump">90,161<span></span>
</td>
<td class="nump">66,769<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AccruedIncomeTaxesCurrent', window );">Income taxes payable</a></td>
<td class="nump">1,324<span></span>
</td>
<td class="nump">32,514<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ConvertibleDebtCurrent', window );">1 percent convertible senior notes</a></td>
<td class="nump">293,161<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="top.Show.showAR( this, 'defref_ions_LongTermObligationsCurrent', window );">Current portion of long-term obligations</a></td>
<td class="nump">7,301<span></span>
</td>
<td class="nump">2,026<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ContractWithCustomerLiabilityCurrent', window );">Current portion of deferred contract revenue</a></td>
<td class="nump">108,376<span></span>
</td>
<td class="nump">118,272<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_LiabilitiesCurrent', window );">Total current liabilities</a></td>
<td class="nump">583,250<span></span>
</td>
<td class="nump">273,005<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ContractWithCustomerLiabilityNoncurrent', window );">Long-term deferred contract revenue</a></td>
<td class="nump">424,046<span></span>
</td>
<td class="nump">490,060<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_LongTermObligationsNoncurrent', window );">Long-term obligations, less current portion</a></td>
<td class="nump">23,409<span></span>
</td>
<td class="nump">15,543<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_LongTermLoansFromBank', window );">Long-term mortgage debt</a></td>
<td class="nump">59,984<span></span>
</td>
<td class="nump">59,913<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_Liabilities', window );">Total liabilities</a></td>
<td class="nump">1,546,408<span></span>
</td>
<td class="nump">1,548,565<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="top.Show.showAR( this, 'defref_us-gaap_CommonStockValue', window );">Common stock, $0.001 par value; 300,000,000 shares authorized, 140,365,594 and 140,339,615 shares issued and outstanding at December 31, 2020 and December 31, 2019, respectively</a></td>
<td class="nump">140<span></span>
</td>
<td class="nump">140<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AdditionalPaidInCapitalCommonStock', window );">Additional paid-in capital</a></td>
<td class="nump">2,113,646<span></span>
</td>
<td class="nump">2,203,778<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AccumulatedOtherComprehensiveIncomeLossNetOfTax', window );">Accumulated other comprehensive loss</a></td>
<td class="num">(21,071)<span></span>
</td>
<td class="num">(25,290)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RetainedEarningsAccumulatedDeficit', window );">Accumulated deficit</a></td>
<td class="num">(1,249,368)<span></span>
</td>
<td class="num">(707,534)<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_StockholdersEquity', window );">Total Ionis stockholders' equity</a></td>
<td class="nump">843,347<span></span>
</td>
<td class="nump">1,471,094<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_MinorityInterest', window );">Noncontrolling interest in Akcea Therapeutics, Inc.</a></td>
<td class="nump">0<span></span>
</td>
<td class="nump">213,453<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest', window );">Total stockholders' equity</a></td>
<td class="nump">843,347<span></span>
</td>
<td class="nump">1,684,547<span></span>
</td>
</tr>
<tr class="rou">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_LiabilitiesAndStockholdersEquity', window );">Total liabilities and stockholders' equity</a></td>
<td class="nump">2,389,755<span></span>
</td>
<td class="nump">3,233,112<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="top.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="top.Show.showAR( this, 'defref_us-gaap_ConvertibleDebtNoncurrent', window );">Convertible senior notes</a></td>
<td class="nump">455,719<span></span>
</td>
<td class="nump">434,711<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="top.Show.showAR( this, 'defref_us-gaap_ConvertibleDebtCurrent', window );">1 percent convertible senior notes</a></td>
<td class="nump">293,200<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ConvertibleDebtNoncurrent', window );">Convertible senior notes</a></td>
<td class="nump">$ 0<span></span>
</td>
<td class="nump">$ 275,333<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of long-term debt, excluding convertible debt, and lease obligations, classified as current, and other current liabilities.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of long-term debt and lease obligation, classified as noncurrent.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</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_AccountsPayableCurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02.19(a))<br> -URI http://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 944<br> -SubTopic 210<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-03(a)(15)(b)(1))<br> -URI http://asc.fasb.org/extlink&amp;oid=120400017&amp;loc=d3e572229-122910<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 942<br> -SubTopic 210<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-03(15)(1))<br> -URI http://asc.fasb.org/extlink&amp;oid=120398452&amp;loc=d3e534808-122878<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(20))<br> -URI http://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02.20)<br> -URI http://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Accumulated change in equity from transactions and other events and circumstances from non-owner sources, net of tax effect, at period end. Excludes Net Income (Loss), and accumulated changes in equity from transactions resulting from investments by owners and distributions to owners. Includes foreign currency translation items, certain pension adjustments, unrealized gains and losses on certain investments in debt and equity securities, other than temporary impairment (OTTI) losses related to factors other than credit losses on available-for-sale and held-to-maturity debt securities that an entity does not intend to sell and it is not more likely than not that the entity will be required to sell before recovery of the amortized cost basis, as well as changes in the fair value of derivatives related to the effective portion of a designated cash flow hedge.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(30)(a)(4))<br> -URI http://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section 45<br> -Paragraph 11<br> -URI http://asc.fasb.org/extlink&amp;oid=121641772&amp;loc=d3e637-108580<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 944<br> -SubTopic 210<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-03(a)(23)(a)(3))<br> -URI http://asc.fasb.org/extlink&amp;oid=120400017&amp;loc=d3e572229-122910<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section 45<br> -Paragraph 14A<br> -URI http://asc.fasb.org/extlink&amp;oid=121641772&amp;loc=SL7669686-108580<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 944<br> -SubTopic 40<br> -Section 65<br> -Paragraph 2<br> -Subparagraph (h)(2)<br> -URI http://asc.fasb.org/extlink&amp;oid=121370832&amp;loc=SL117420844-207641<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 944<br> -SubTopic 40<br> -Section 65<br> -Paragraph 2<br> -Subparagraph (g)(2)(ii)<br> -URI http://asc.fasb.org/extlink&amp;oid=121370832&amp;loc=SL117420844-207641<br><br>Reference 7: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section 45<br> -Paragraph 14<br> -URI http://asc.fasb.org/extlink&amp;oid=121641772&amp;loc=d3e681-108580<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(30)(a)(1))<br> -URI http://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>
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<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
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<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 942<br> -SubTopic 210<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-03(11))<br> -URI http://asc.fasb.org/extlink&amp;oid=120398452&amp;loc=d3e534808-122878<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 235<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.4-08(g)(1)(ii))<br> -URI http://asc.fasb.org/extlink&amp;oid=120395691&amp;loc=d3e23780-122690<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 825<br> -SubTopic 10<br> -Section 50<br> -Paragraph 28<br> -Subparagraph (f)<br> -URI http://asc.fasb.org/extlink&amp;oid=75031198&amp;loc=d3e14064-108612<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 810<br> -SubTopic 10<br> -Section 50<br> -Paragraph 3<br> -Subparagraph (bb)<br> -URI http://asc.fasb.org/extlink&amp;oid=121559654&amp;loc=d3e5710-111685<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 810<br> -SubTopic 10<br> -Section 45<br> -Paragraph 25<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=116870748&amp;loc=SL6758485-165988<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (d)<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e8933-108599<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 22<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e8736-108599<br><br>Reference 8: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 944<br> -SubTopic 210<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-03(a)(12))<br> -URI http://asc.fasb.org/extlink&amp;oid=120400017&amp;loc=d3e572229-122910<br><br>Reference 9: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 323<br> -SubTopic 10<br> -Section 50<br> -Paragraph 3<br> -Subparagraph (c)<br> -URI http://asc.fasb.org/extlink&amp;oid=114001798&amp;loc=d3e33918-111571<br><br>Reference 10: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 30<br> -Subparagraph (c)<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e8906-108599<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Sum of the carrying amounts as of the balance sheet date of all assets that are expected to be realized in cash, sold, or consumed within one year (or the normal operating cycle, if longer). Assets are probable future economic benefits obtained or controlled by an entity as a result of past transactions or events.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section 45<br> -Paragraph 3<br> -URI http://asc.fasb.org/extlink&amp;oid=121566466&amp;loc=d3e6801-107765<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 825<br> -SubTopic 10<br> -Section 50<br> -Paragraph 28<br> -Subparagraph (f)<br> -URI http://asc.fasb.org/extlink&amp;oid=75031198&amp;loc=d3e14064-108612<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 810<br> -SubTopic 10<br> -Section 45<br> -Paragraph 25<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=116870748&amp;loc=SL6758485-165988<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 323<br> -SubTopic 10<br> -Section 50<br> -Paragraph 3<br> -Subparagraph (c)<br> -URI http://asc.fasb.org/extlink&amp;oid=114001798&amp;loc=d3e33918-111571<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 810<br> -SubTopic 10<br> -Section 50<br> -Paragraph 3<br> -Subparagraph (bb)<br> -URI http://asc.fasb.org/extlink&amp;oid=121559654&amp;loc=d3e5710-111685<br><br>Reference 6: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02.9)<br> -URI http://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 235<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.4-08(g)(1)(ii))<br> -URI http://asc.fasb.org/extlink&amp;oid=120395691&amp;loc=d3e23780-122690<br><br>Reference 8: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section 45<br> -Paragraph 1<br> -URI http://asc.fasb.org/extlink&amp;oid=121566466&amp;loc=d3e6676-107765<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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_AvailableForSaleSecuritiesDebtSecuritiesCurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 326<br> -SubTopic 30<br> -Section 45<br> -Paragraph 1<br> -URI http://asc.fasb.org/extlink&amp;oid=121558606&amp;loc=SL82898722-210454<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 320<br> -SubTopic 10<br> -Section 45<br> -Paragraph 2<br> -URI http://asc.fasb.org/extlink&amp;oid=121553693&amp;loc=d3e26626-111562<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AvailableForSaleSecuritiesDebtSecuritiesCurrent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_CashAndCashEquivalentsAtCarryingValue">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 4<br> -URI http://asc.fasb.org/extlink&amp;oid=121586364&amp;loc=d3e3044-108585<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section 45<br> -Paragraph 1<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=121566466&amp;loc=d3e6676-107765<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02.1)<br> -URI http://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(29))<br> -URI http://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 45<br> -Paragraph 1<br> -URI http://asc.fasb.org/extlink&amp;oid=121556615&amp;loc=SL49130531-203044<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 45<br> -Paragraph 3<br> -URI http://asc.fasb.org/extlink&amp;oid=121556615&amp;loc=SL49130533-203044<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 50<br> -Paragraph 8<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=121604090&amp;loc=SL49130549-203045<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 45<br> -Paragraph 1<br> -URI http://asc.fasb.org/extlink&amp;oid=121556615&amp;loc=SL49130531-203044<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 45<br> -Paragraph 2<br> -URI http://asc.fasb.org/extlink&amp;oid=121556615&amp;loc=SL49130532-203044<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 50<br> -Paragraph 8<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=121604090&amp;loc=SL49130549-203045<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 45<br> -Paragraph 2<br> -URI http://asc.fasb.org/extlink&amp;oid=121556615&amp;loc=SL49130532-203044<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 45<br> -Paragraph 1<br> -URI http://asc.fasb.org/extlink&amp;oid=121556615&amp;loc=SL49130531-203044<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 50<br> -Paragraph 8<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=121604090&amp;loc=SL49130549-203045<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(19))<br> -URI http://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02.22)<br> -URI http://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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_DeferredIncomeTaxAssetsNet">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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, with jurisdictional netting.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 45<br> -Paragraph 6<br> -URI http://asc.fasb.org/extlink&amp;oid=120406818&amp;loc=d3e31931-109318<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 45<br> -Paragraph 4<br> -URI http://asc.fasb.org/extlink&amp;oid=120406818&amp;loc=d3e31917-109318<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DeferredIncomeTaxAssetsNet</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>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_EmployeeRelatedLiabilitiesCurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02.20)<br> -URI http://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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_FiniteLivedIntangibleAssetsNet">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount after amortization of assets, excluding financial assets and goodwill, lacking physical substance with a finite life.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 926<br> -SubTopic 20<br> -Section 50<br> -Paragraph 5<br> -URI http://asc.fasb.org/extlink&amp;oid=120154696&amp;loc=d3e54445-107959<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 350<br> -SubTopic 30<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (a)(1)<br> -URI http://asc.fasb.org/extlink&amp;oid=66006027&amp;loc=d3e16323-109275<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_FiniteLivedIntangibleAssetsNet</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_InventoryNet">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section 45<br> -Paragraph 1<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=121566466&amp;loc=d3e6676-107765<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02.6(a))<br> -URI http://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 810<br> -SubTopic 10<br> -Section 45<br> -Paragraph 25<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=116870748&amp;loc=SL6758485-165988<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 825<br> -SubTopic 10<br> -Section 50<br> -Paragraph 28<br> -Subparagraph (f)<br> -URI http://asc.fasb.org/extlink&amp;oid=75031198&amp;loc=d3e14064-108612<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 810<br> -SubTopic 10<br> -Section 50<br> -Paragraph 3<br> -Subparagraph (bb)<br> -URI http://asc.fasb.org/extlink&amp;oid=121559654&amp;loc=d3e5710-111685<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02.19-26)<br> -URI http://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 810<br> -SubTopic 10<br> -Section 50<br> -Paragraph 3<br> -Subparagraph (c)<br> -URI http://asc.fasb.org/extlink&amp;oid=121559654&amp;loc=d3e5710-111685<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 323<br> -SubTopic 10<br> -Section 50<br> -Paragraph 3<br> -Subparagraph (c)<br> -URI http://asc.fasb.org/extlink&amp;oid=114001798&amp;loc=d3e33918-111571<br><br>Reference 7: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 30<br> -Subparagraph (d)<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e8906-108599<br><br>Reference 8: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 235<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.4-08(g)(1)(ii))<br> -URI http://asc.fasb.org/extlink&amp;oid=120395691&amp;loc=d3e23780-122690<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of liabilities and equity items, including the portion of equity attributable to noncontrolling interests, if any.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 323<br> -SubTopic 10<br> -Section 50<br> -Paragraph 3<br> -Subparagraph (c)<br> -URI http://asc.fasb.org/extlink&amp;oid=114001798&amp;loc=d3e33918-111571<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 942<br> -SubTopic 210<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-03(23))<br> -URI http://asc.fasb.org/extlink&amp;oid=120398452&amp;loc=d3e534808-122878<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 944<br> -SubTopic 210<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-03(a)(25))<br> -URI http://asc.fasb.org/extlink&amp;oid=120400017&amp;loc=d3e572229-122910<br><br>Reference 4: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 235<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.4-08(g)(1)(ii))<br> -URI http://asc.fasb.org/extlink&amp;oid=120395691&amp;loc=d3e23780-122690<br><br>Reference 5: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(32))<br> -URI http://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br><br>Reference 6: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 825<br> -SubTopic 10<br> -Section 50<br> -Paragraph 28<br> -Subparagraph (f)<br> -URI http://asc.fasb.org/extlink&amp;oid=75031198&amp;loc=d3e14064-108612<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_LiabilitiesAndStockholdersEquity</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_LiabilitiesCurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Total obligations incurred as part of normal operations that are expected to be paid during the following twelve months or within one business cycle, if longer.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 810<br> -SubTopic 10<br> -Section 50<br> -Paragraph 3<br> -Subparagraph (bb)<br> -URI http://asc.fasb.org/extlink&amp;oid=121559654&amp;loc=d3e5710-111685<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 825<br> -SubTopic 10<br> -Section 50<br> -Paragraph 28<br> -Subparagraph (f)<br> -URI http://asc.fasb.org/extlink&amp;oid=75031198&amp;loc=d3e14064-108612<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 810<br> -SubTopic 10<br> -Section 45<br> -Paragraph 25<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=116870748&amp;loc=SL6758485-165988<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 235<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.4-08(g)(1)(ii))<br> -URI http://asc.fasb.org/extlink&amp;oid=120395691&amp;loc=d3e23780-122690<br><br>Reference 5: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02.21)<br> -URI http://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 810<br> -SubTopic 10<br> -Section 50<br> -Paragraph 3<br> -Subparagraph (c)<br> -URI http://asc.fasb.org/extlink&amp;oid=121559654&amp;loc=d3e5710-111685<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 323<br> -SubTopic 10<br> -Section 50<br> -Paragraph 3<br> -Subparagraph (c)<br> -URI http://asc.fasb.org/extlink&amp;oid=114001798&amp;loc=d3e33918-111571<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_LiabilitiesCurrent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_LiabilitiesCurrentAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_LiabilitiesCurrentAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_LongTermLoansFromBank">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(22))<br> -URI http://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 942<br> -SubTopic 210<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-03(16))<br> -URI http://asc.fasb.org/extlink&amp;oid=120398452&amp;loc=d3e534808-122878<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 944<br> -SubTopic 210<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-03(a)(16)(a)(2))<br> -URI http://asc.fasb.org/extlink&amp;oid=120400017&amp;loc=d3e572229-122910<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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_MinorityInterest">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Total of all stockholders' equity (deficit) items, net of receivables from officers, directors, owners, and affiliates of the entity which is directly or indirectly attributable to that ownership interest in subsidiary equity which is not attributable to the parent (that is, noncontrolling interest, previously referred to as minority interest).</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 944<br> -SubTopic 210<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-03(a)(24))<br> -URI http://asc.fasb.org/extlink&amp;oid=120400017&amp;loc=d3e572229-122910<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 825<br> -SubTopic 10<br> -Section 50<br> -Paragraph 28<br> -Subparagraph (f)<br> -URI http://asc.fasb.org/extlink&amp;oid=75031198&amp;loc=d3e14064-108612<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02.31)<br> -URI http://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 323<br> -SubTopic 10<br> -Section 50<br> -Paragraph 3<br> -Subparagraph (c)<br> -URI http://asc.fasb.org/extlink&amp;oid=114001798&amp;loc=d3e33918-111571<br><br>Reference 5: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 942<br> -SubTopic 210<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-03(22))<br> -URI http://asc.fasb.org/extlink&amp;oid=120398452&amp;loc=d3e534808-122878<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 235<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.4-08(g)(1)(ii))<br> -URI http://asc.fasb.org/extlink&amp;oid=120395691&amp;loc=d3e23780-122690<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_MinorityInterest</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>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_OtherAssetsCurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of current assets classified as other.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02.8)<br> -URI http://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of noncurrent assets classified as other.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02.17)<br> -URI http://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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_PropertyPlantAndEquipmentNet">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(14))<br> -URI http://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 360<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -URI http://asc.fasb.org/extlink&amp;oid=6391035&amp;loc=d3e2868-110229<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 944<br> -SubTopic 210<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-03(a)(8))<br> -URI http://asc.fasb.org/extlink&amp;oid=120400017&amp;loc=d3e572229-122910<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(13))<br> -URI http://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The cumulative amount of the reporting entity's undistributed earnings or deficit.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(30)(a)(3))<br> -URI http://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 65<br> -Paragraph 15<br> -Subparagraph (g)(2)<br> -URI http://asc.fasb.org/extlink&amp;oid=121322162&amp;loc=SL121327923-165333<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 944<br> -SubTopic 210<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-03(a)(23)(a)(4))<br> -URI http://asc.fasb.org/extlink&amp;oid=120400017&amp;loc=d3e572229-122910<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 944<br> -SubTopic 40<br> -Section 65<br> -Paragraph 2<br> -Subparagraph (h)(2)<br> -URI http://asc.fasb.org/extlink&amp;oid=121370832&amp;loc=SL117420844-207641<br><br>Reference 5: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 505<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.3-04)<br> -URI http://asc.fasb.org/extlink&amp;oid=120397183&amp;loc=d3e187085-122770<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 944<br> -SubTopic 40<br> -Section 65<br> -Paragraph 2<br> -Subparagraph (g)(2)(i)<br> -URI http://asc.fasb.org/extlink&amp;oid=121370832&amp;loc=SL117420844-207641<br></p></div>
<a href="javascript:void(0);" onclick="top.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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Total of all stockholders' equity (deficit) items, net of receivables from officers, directors, owners, and affiliates of the entity which are attributable to the parent. The amount of the economic entity's stockholders' equity attributable to the parent excludes the amount of stockholders' equity which is allocable to that ownership interest in subsidiary equity which is not attributable to the parent (noncontrolling interest, minority interest). This excludes temporary equity and is sometimes called permanent equity.</p></div>
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<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_StockholdersEquityAbstract</td>
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<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of stockholders' equity (deficit), net of receivables from officers, directors, owners, and affiliates of the entity, attributable to both the parent and noncontrolling interests. Amount excludes temporary equity. Alternate caption for the concept is permanent equity.</p></div>
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<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest</td>
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<span style="display: none;">v3.20.4</span><table class="report" border="0" cellspacing="2" id="idm140142726891768">
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<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, 2020</div></th>
<th class="th"><div>Dec. 31, 2019</div></th>
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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="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_LiabilitiesAndStockholdersEquityAbstract', window );"><strong>LIABILITIES AND STOCKHOLDERS' EQUITY</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_DebtInstrumentInterestRateStatedPercentage', window );">Interest rate on convertible senior notes</a></td>
<td class="nump">0.125%<span></span>
</td>
<td class="nump">0.125%<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_LiabilitiesAndStockholdersEquityAbstract', window );"><strong>LIABILITIES AND STOCKHOLDERS' EQUITY</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_DebtInstrumentInterestRateStatedPercentage', window );">Interest rate on convertible senior notes</a></td>
<td class="nump">1.00%<span></span>
</td>
<td class="nump">1.00%<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_CommonStockParOrStatedValuePerShare">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(29))<br> -URI http://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_CommonStockParOrStatedValuePerShare</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>num: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_CommonStockSharesAuthorized">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(29))<br> -URI http://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(29))<br> -URI http://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_CommonStockSharesIssued</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:sharesItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_CommonStockSharesOutstanding">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 505<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -URI http://asc.fasb.org/extlink&amp;oid=109259400&amp;loc=d3e21463-112644<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(29))<br> -URI http://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>
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<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:sharesItemType</td>
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<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
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<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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02.22(a)(1))<br> -URI http://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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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<td>num:percentItemType</td>
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<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
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<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_LiabilitiesAndStockholdersEquityAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_LiabilitiesAndStockholdersEquityAbstract</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<td><strong> Period Type:</strong></td>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_StockholdersEquityAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_StockholdersEquityAbstract</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<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_DebtInstrumentAxis=ions_ConvertibleSeniorNotes0125PercentMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes0125PercentMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
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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_us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes1PercentMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes1PercentMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
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<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
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<td><strong> Balance Type:</strong></td>
<td></td>
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<tr>
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<span style="display: none;">v3.20.4</span><table class="report" border="0" cellspacing="2" id="idm140142741351944">
<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, 2020</div></th>
<th class="th"><div>Dec. 31, 2019</div></th>
<th class="th"><div>Dec. 31, 2018</div></th>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenuesAbstract', window );"><strong>Revenue:</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">$ 729,264<span></span>
</td>
<td class="nump">$ 1,122,599<span></span>
</td>
<td class="nump">$ 599,674<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="top.Show.showAR( this, 'defref_us-gaap_CostOfGoodsAndServicesSold', window );">Cost of products sold</a></td>
<td class="nump">11,947<span></span>
</td>
<td class="nump">4,384<span></span>
</td>
<td class="nump">1,820<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_ResearchDevelopmentAndPatentExpense', window );">Research, development and patent</a></td>
<td class="nump">535,077<span></span>
</td>
<td class="nump">465,688<span></span>
</td>
<td class="nump">414,604<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_SellingGeneralAndAdministrativeExpense', window );">Selling, general and administrative</a></td>
<td class="nump">354,322<span></span>
</td>
<td class="nump">286,644<span></span>
</td>
<td class="nump">244,622<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_CostsAndExpenses', window );">Total operating expenses</a></td>
<td class="nump">901,346<span></span>
</td>
<td class="nump">756,716<span></span>
</td>
<td class="nump">661,046<span></span>
</td>
</tr>
<tr class="rou">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_OperatingIncomeLoss', window );">Income (loss) from operations</a></td>
<td class="num">(172,082)<span></span>
</td>
<td class="nump">365,883<span></span>
</td>
<td class="num">(61,372)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="top.Show.showAR( this, 'defref_us-gaap_InvestmentIncomeNet', window );">Investment income</a></td>
<td class="nump">30,562<span></span>
</td>
<td class="nump">52,013<span></span>
</td>
<td class="nump">30,397<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_InterestExpense', window );">Interest expense</a></td>
<td class="num">(44,990)<span></span>
</td>
<td class="num">(48,768)<span></span>
</td>
<td class="num">(44,789)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_GainLossOnInvestments', window );">Gain (loss) on investments</a></td>
<td class="nump">16,540<span></span>
</td>
<td class="nump">192<span></span>
</td>
<td class="num">(210)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_GainsLossesOnExtinguishmentOfDebt', window );">Loss on early retirement of debt</a></td>
<td class="nump">0<span></span>
</td>
<td class="num">(21,865)<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="top.Show.showAR( this, 'defref_us-gaap_OtherNonoperatingIncomeExpense', window );">Other expenses</a></td>
<td class="num">(62)<span></span>
</td>
<td class="num">(686)<span></span>
</td>
<td class="num">(182)<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesMinorityInterestAndIncomeLossFromEquityMethodInvestments', window );">Income (loss) before income tax benefit (expense)</a></td>
<td class="num">(170,032)<span></span>
</td>
<td class="nump">346,769<span></span>
</td>
<td class="num">(76,156)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_IncomeTaxExpenseBenefit', window );">Income tax benefit (expense)</a></td>
<td class="num">(316,734)<span></span>
</td>
<td class="num">(43,507)<span></span>
</td>
<td class="nump">291,141<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ProfitLoss', window );">Net income (loss)</a></td>
<td class="num">(486,766)<span></span>
</td>
<td class="nump">303,262<span></span>
</td>
<td class="nump">214,985<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_NetIncomeLossAttributableToNoncontrollingInterest', window );">Net (income) loss attributable to noncontrolling interest in Akcea Therapeutics, Inc.</a></td>
<td class="nump">35,480<span></span>
</td>
<td class="num">(9,116)<span></span>
</td>
<td class="nump">58,756<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_NetIncomeLoss', window );">Net income (loss) attributable to Ionis Pharmaceuticals, Inc. common stockholders</a></td>
<td class="num">$ (451,286)<span></span>
</td>
<td class="nump">$ 294,146<span></span>
</td>
<td class="nump">$ 273,741<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_EarningsPerShareBasic', window );">Basic net income (loss) per share (in dollars per share)</a></td>
<td class="num">$ (3.23)<span></span>
</td>
<td class="nump">$ 2.12<span></span>
</td>
<td class="nump">$ 2.09<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_WeightedAverageNumberOfSharesOutstandingBasic', window );">Shares used in computing basic net income (loss) per share (in shares)</a></td>
<td class="nump">139,612<span></span>
</td>
<td class="nump">139,998<span></span>
</td>
<td class="nump">132,320<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_EarningsPerShareDiluted', window );">Diluted net income (loss) per share (in dollars per share)</a></td>
<td class="num">$ (3.23)<span></span>
</td>
<td class="nump">$ 2.08<span></span>
</td>
<td class="nump">$ 2.07<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding', window );">Shares used in computing diluted net income (loss) per share (in shares)</a></td>
<td class="nump">139,612<span></span>
</td>
<td class="nump">142,872<span></span>
</td>
<td class="nump">134,056<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="top.Show.showAR( this, 'defref_us-gaap_RevenuesAbstract', window );"><strong>Revenue:</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">$ 364,699<span></span>
</td>
<td class="nump">$ 352,450<span></span>
</td>
<td class="nump">$ 254,922<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="top.Show.showAR( this, 'defref_us-gaap_RevenuesAbstract', window );"><strong>Revenue:</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">286,583<span></span>
</td>
<td class="nump">292,992<span></span>
</td>
<td class="nump">237,930<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_srt_ProductOrServiceAxis=us-gaap_ProductMember', window );">Product Sales, Net [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenuesAbstract', window );"><strong>Revenue:</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">69,999<span></span>
</td>
<td class="nump">42,253<span></span>
</td>
<td class="nump">2,237<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_srt_ProductOrServiceAxis=ions_LicensingAndOtherRoyaltiesMember', window );">Licensing and Other Royalty Revenue [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenuesAbstract', window );"><strong>Revenue:</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">8,117<span></span>
</td>
<td class="nump">17,205<span></span>
</td>
<td class="nump">14,755<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_srt_ProductOrServiceAxis=ions_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember', window );">Research and Development Revenue Under Collaborative 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>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenuesAbstract', window );"><strong>Revenue:</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">$ 364,565<span></span>
</td>
<td class="nump">$ 770,149<span></span>
</td>
<td class="nump">$ 344,752<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_ResearchDevelopmentAndPatentExpense">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 924<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 11.L)<br> -URI http://asc.fasb.org/extlink&amp;oid=6472922&amp;loc=d3e499488-122856<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.5-03.2(a),(d))<br> -URI http://asc.fasb.org/extlink&amp;oid=120395209&amp;loc=SL114868664-224227<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.5-03)<br> -URI http://asc.fasb.org/extlink&amp;oid=120395209&amp;loc=SL114868664-224227<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 250<br> -SubTopic 10<br> -Section 50<br> -Paragraph 3<br> -URI http://asc.fasb.org/extlink&amp;oid=109234566&amp;loc=d3e22583-107794<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 250<br> -SubTopic 10<br> -Section 50<br> -Paragraph 11<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=109234566&amp;loc=d3e22694-107794<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 45<br> -Paragraph 10<br> -URI http://asc.fasb.org/extlink&amp;oid=121326447&amp;loc=d3e1448-109256<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 250<br> -SubTopic 10<br> -Section 50<br> -Paragraph 4<br> -URI http://asc.fasb.org/extlink&amp;oid=109234566&amp;loc=d3e22595-107794<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 250<br> -SubTopic 10<br> -Section 50<br> -Paragraph 11<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=109234566&amp;loc=d3e22694-107794<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 45<br> -Paragraph 7<br> -URI http://asc.fasb.org/extlink&amp;oid=121326447&amp;loc=d3e1337-109256<br><br>Reference 7: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 55<br> -Paragraph 52<br> -URI http://asc.fasb.org/extlink&amp;oid=120380238&amp;loc=d3e4984-109258<br><br>Reference 8: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 944<br> -SubTopic 220<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-04(23))<br> -URI http://asc.fasb.org/extlink&amp;oid=120400993&amp;loc=SL114874131-224263<br><br>Reference 9: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 55<br> -Paragraph 15<br> -URI http://asc.fasb.org/extlink&amp;oid=120380238&amp;loc=d3e3842-109258<br><br>Reference 10: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 250<br> -SubTopic 10<br> -Section 50<br> -Paragraph 7<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=109234566&amp;loc=d3e22644-107794<br><br>Reference 11: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=6371337&amp;loc=d3e3550-109257<br><br>Reference 12: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.5-03(25))<br> -URI http://asc.fasb.org/extlink&amp;oid=120395209&amp;loc=SL114868664-224227<br><br>Reference 13: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 45<br> -Paragraph 2<br> -URI http://asc.fasb.org/extlink&amp;oid=121326447&amp;loc=d3e1252-109256<br><br>Reference 14: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 45<br> -Paragraph 60B<br> -Subparagraph (d)<br> -URI http://asc.fasb.org/extlink&amp;oid=121326447&amp;loc=SL5780133-109256<br><br>Reference 15: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 942<br> -SubTopic 220<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-04(27))<br> -URI http://asc.fasb.org/extlink&amp;oid=120399700&amp;loc=SL114874048-224260<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>num: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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ Details</a><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>num: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_GainLossOnInvestments">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of realized and unrealized gain (loss) on investment.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 320<br> -SubTopic 10<br> -Section 50<br> -Paragraph 10<br> -Subparagraph (c)<br> -URI http://asc.fasb.org/extlink&amp;oid=121645371&amp;loc=d3e27405-111563<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.5-03.7(c),9(a))<br> -URI http://asc.fasb.org/extlink&amp;oid=120395209&amp;loc=SL114868664-224227<br><br>Reference 3: http://www.xbrl.org/2003/role/recommendedDisclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=121586364&amp;loc=d3e3602-108585<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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_GainsLossesOnExtinguishmentOfDebt">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 50<br> -Section 40<br> -Paragraph 4<br> -URI http://asc.fasb.org/extlink&amp;oid=117329964&amp;loc=d3e12355-112629<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 50<br> -Section 40<br> -Paragraph 2<br> -URI http://asc.fasb.org/extlink&amp;oid=117329964&amp;loc=d3e12317-112629<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=121586364&amp;loc=d3e3602-108585<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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_IncomeLossFromContinuingOperationsBeforeIncomeTaxesMinorityInterestAndIncomeLossFromEquityMethodInvestments">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of income (loss) from continuing operations before deduction of income tax expense (benefit) and income (loss) attributable to noncontrolling interest, and addition of income (loss) from equity method investments.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (f)<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e8933-108599<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (c)<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e8933-108599<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 30<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e8906-108599<br><br>Reference 4: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 31<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e8924-108599<br><br>Reference 5: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 235<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.4-08.(h)(1)(i))<br> -URI http://asc.fasb.org/extlink&amp;oid=120395691&amp;loc=d3e23780-122690<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 22<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e8736-108599<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesMinorityInterestAndIncomeLossFromEquityMethodInvestments</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB TOPIC 6.I.7)<br> -URI http://asc.fasb.org/extlink&amp;oid=116825942&amp;loc=d3e330036-122817<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 10<br> -URI http://asc.fasb.org/extlink&amp;oid=84230637&amp;loc=d3e32672-109319<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 22<br> -Subparagraph (h)<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e8736-108599<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 235<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.4-08(h))<br> -URI http://asc.fasb.org/extlink&amp;oid=120395691&amp;loc=d3e23780-122690<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 250<br> -SubTopic 10<br> -Section 50<br> -Paragraph 9<br> -URI http://asc.fasb.org/extlink&amp;oid=109234566&amp;loc=d3e22663-107794<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 20<br> -Section 45<br> -Paragraph 2<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=120385591&amp;loc=d3e38679-109324<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 944<br> -SubTopic 220<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-04(9))<br> -URI http://asc.fasb.org/extlink&amp;oid=120400993&amp;loc=SL114874131-224263<br><br>Reference 8: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 250<br> -SubTopic 10<br> -Section 50<br> -Paragraph 8<br> -URI http://asc.fasb.org/extlink&amp;oid=109234566&amp;loc=d3e22658-107794<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 835<br> -SubTopic 20<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=6450988&amp;loc=d3e26243-108391<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 835<br> -SubTopic 30<br> -Section 45<br> -Paragraph 3<br> -URI http://asc.fasb.org/extlink&amp;oid=119993939&amp;loc=d3e28555-108399<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 22<br> -Subparagraph (d)<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e8736-108599<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (210.5-03(11))<br> -URI http://asc.fasb.org/extlink&amp;oid=120395209&amp;loc=SL114868664-224227<br><br>Reference 5: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 942<br> -SubTopic 220<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-04.9)<br> -URI http://asc.fasb.org/extlink&amp;oid=120399700&amp;loc=SL114874048-224260<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.5-03.7(a),(b))<br> -URI http://asc.fasb.org/extlink&amp;oid=120395209&amp;loc=SL114868664-224227<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.5-03.8)<br> -URI http://asc.fasb.org/extlink&amp;oid=120395209&amp;loc=SL114868664-224227<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>
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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>
</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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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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-SubTopic 10<br> -Section 50<br> -Paragraph 30<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e8906-108599<br><br>Reference 18: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 250<br> -SubTopic 10<br> -Section 50<br> -Paragraph 3<br> -URI http://asc.fasb.org/extlink&amp;oid=109234566&amp;loc=d3e22583-107794<br><br>Reference 19: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 235<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.4-08(g)(1)(ii))<br> -URI http://asc.fasb.org/extlink&amp;oid=120395691&amp;loc=d3e23780-122690<br><br>Reference 20: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 45<br> -Paragraph 60B<br> -Subparagraph (a)<br> -URI 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<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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_NetIncomeLossAttributableToNoncontrollingInterest">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of Net Income (Loss) attributable to noncontrolling interest.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section 45<br> -Paragraph 1B<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=121641772&amp;loc=SL7669625-108580<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 810<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1A<br> -Subparagraph (a)(2)<br> -URI http://asc.fasb.org/extlink&amp;oid=109239629&amp;loc=SL4573702-111684<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 250<br> -SubTopic 10<br> -Section 50<br> -Paragraph 8<br> -URI http://asc.fasb.org/extlink&amp;oid=109234566&amp;loc=d3e22658-107794<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section 45<br> -Paragraph 1A<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=121641772&amp;loc=SL7669619-108580<br><br>Reference 5: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 810<br> -SubTopic 10<br> -Section 55<br> -Paragraph 4J<br> -URI http://asc.fasb.org/extlink&amp;oid=120409616&amp;loc=SL4591551-111686<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 250<br> -SubTopic 10<br> -Section 50<br> -Paragraph 9<br> -URI http://asc.fasb.org/extlink&amp;oid=109234566&amp;loc=d3e22663-107794<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_NetIncomeLossAttributableToNoncontrollingInterest</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>
</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_OperatingIncomeLoss">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 31<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e8924-108599<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 30<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e8906-108599<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (c)<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e8933-108599<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (f)<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e8933-108599<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 22<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e8736-108599<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.5-03.9)<br> -URI http://asc.fasb.org/extlink&amp;oid=120395209&amp;loc=SL114868664-224227<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ProfitLoss">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The consolidated profit or loss for the period, net of income taxes, including the portion attributable to the noncontrolling interest.</p></div>
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-Name Accounting Standards Codification<br> -Topic 810<br> -SubTopic 10<br> -Section 45<br> -Paragraph 19<br> -URI http://asc.fasb.org/extlink&amp;oid=108774443&amp;loc=SL4569616-111683<br><br>Reference 18: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 323<br> -SubTopic 10<br> -Section 50<br> -Paragraph 3<br> -Subparagraph (c)<br> -URI http://asc.fasb.org/extlink&amp;oid=114001798&amp;loc=d3e33918-111571<br><br>Reference 19: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (f)<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e8933-108599<br><br>Reference 20: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 810<br> -SubTopic 10<br> -Section 55<br> -Paragraph 4K<br> -URI http://asc.fasb.org/extlink&amp;oid=120409616&amp;loc=SL4591552-111686<br><br>Reference 21: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 250<br> -SubTopic 10<br> -Section 50<br> -Paragraph 8<br> -URI http://asc.fasb.org/extlink&amp;oid=109234566&amp;loc=d3e22658-107794<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ProfitLoss</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 30<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e8906-108599<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 40<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e9031-108599<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 41<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e9038-108599<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e8933-108599<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e8933-108599<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=121604090&amp;loc=SL49130543-203045<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 22<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e8736-108599<br><br>Reference 8: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 22<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e8736-108599<br><br>Reference 9: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 42<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e9054-108599<br><br>Reference 10: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 50<br> -Paragraph 5<br> -URI http://asc.fasb.org/extlink&amp;oid=121604090&amp;loc=SL49130545-203045<br><br>Reference 11: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 924<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 11.L)<br> -URI http://asc.fasb.org/extlink&amp;oid=6472922&amp;loc=d3e499488-122856<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_RevenuesAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_RevenuesAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_SellingGeneralAndAdministrativeExpense">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.5-03.4)<br> -URI http://asc.fasb.org/extlink&amp;oid=120395209&amp;loc=SL114868664-224227<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=6371337&amp;loc=d3e3550-109257<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 45<br> -Paragraph 16<br> -URI http://asc.fasb.org/extlink&amp;oid=121326447&amp;loc=d3e1505-109256<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_WeightedAverageNumberOfSharesOutstandingBasic">
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<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=6371337&amp;loc=d3e3550-109257<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 45<br> -Paragraph 10<br> -URI http://asc.fasb.org/extlink&amp;oid=121326447&amp;loc=d3e1448-109256<br></p></div>
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<tr>
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<span style="display: none;">v3.20.4</span><table class="report" border="0" cellspacing="2" id="idm140142739890200">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>CONSOLIDATED STATEMENTS OF COMPREHENSIVE INCOME (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, 2020</div></th>
<th class="th"><div>Dec. 31, 2019</div></th>
<th class="th"><div>Dec. 31, 2018</div></th>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_StatementOfIncomeAndComprehensiveIncomeAbstract', window );"><strong>CONSOLIDATED STATEMENTS OF COMPREHENSIVE INCOME (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>
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<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ProfitLoss', window );">Net income (loss)</a></td>
<td class="num">$ (486,766)<span></span>
</td>
<td class="nump">$ 303,262<span></span>
</td>
<td class="nump">$ 214,985<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_OtherComprehensiveIncomeUnrealizedHoldingGainLossOnSecuritiesArisingDuringPeriodNetOfTax', window );">Unrealized gains (losses) on investments, net of tax</a></td>
<td class="nump">3,729<span></span>
</td>
<td class="nump">6,633<span></span>
</td>
<td class="num">(280)<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="top.Show.showAR( this, 'defref_us-gaap_OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax', window );">Currency translation adjustment</a></td>
<td class="nump">617<span></span>
</td>
<td class="nump">93<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="top.Show.showAR( this, 'defref_ions_OtherComprehensiveIncomeLossAdjustmentsFromPurchaseOfNoncontrollingInterestOfSubsidiary', window );">Adjustments to other comprehensive loss from purchase of noncontrolling interest of Akcea Therapeutics, Inc.</a></td>
<td class="num">(127)<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="top.Show.showAR( this, 'defref_us-gaap_ComprehensiveIncomeNetOfTaxIncludingPortionAttributableToNoncontrollingInterest', window );">Comprehensive income (loss)</a></td>
<td class="num">(482,547)<span></span>
</td>
<td class="nump">309,988<span></span>
</td>
<td class="nump">214,728<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="top.Show.showAR( this, 'defref_us-gaap_ComprehensiveIncomeNetOfTaxAttributableToNoncontrollingInterest', window );">Comprehensive income (loss) attributable to noncontrolling interest in Akcea Therapeutics, Inc.</a></td>
<td class="num">(35,480)<span></span>
</td>
<td class="nump">9,118<span></span>
</td>
<td class="num">(58,781)<span></span>
</td>
</tr>
<tr class="rou">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ComprehensiveIncomeNetOfTax', window );">Comprehensive income (loss) attributable to Ionis Pharmaceuticals, Inc. common stockholders</a></td>
<td class="num">$ (447,067)<span></span>
</td>
<td class="nump">$ 300,870<span></span>
</td>
<td class="nump">$ 273,509<span></span>
</td>
</tr>
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<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Adjustments to other comprehensive income (loss) from purchase of noncontrolling interest of subsidiary.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_OtherComprehensiveIncomeLossAdjustmentsFromPurchaseOfNoncontrollingInterestOfSubsidiary</td>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ComprehensiveIncomeNetOfTax">
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<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 944<br> -SubTopic 220<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-04(22))<br> -URI http://asc.fasb.org/extlink&amp;oid=120400993&amp;loc=SL114874131-224263<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.5-03(24))<br> -URI http://asc.fasb.org/extlink&amp;oid=120395209&amp;loc=SL114868664-224227<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section 45<br> -Paragraph 5<br> -URI http://asc.fasb.org/extlink&amp;oid=121641772&amp;loc=d3e557-108580<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 942<br> -SubTopic 220<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-04(26))<br> -URI http://asc.fasb.org/extlink&amp;oid=120399700&amp;loc=SL114874048-224260<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section 45<br> -Paragraph 1B<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=121641772&amp;loc=SL7669625-108580<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section 45<br> -Paragraph 1A<br> -Subparagraph (c)<br> -URI http://asc.fasb.org/extlink&amp;oid=121641772&amp;loc=SL7669619-108580<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>
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<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<td><strong> Balance Type:</strong></td>
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<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount after tax of increase (decrease) in equity from transactions and other events and circumstances from net income (loss) and other comprehensive income (loss), attributable to noncontrolling interests. Excludes changes in equity resulting from investments by owners and distributions to owners.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section 45<br> -Paragraph 1B<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=121641772&amp;loc=SL7669625-108580<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 944<br> -SubTopic 220<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-04(21))<br> -URI http://asc.fasb.org/extlink&amp;oid=120400993&amp;loc=SL114874131-224263<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 942<br> -SubTopic 220<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-04(25))<br> -URI http://asc.fasb.org/extlink&amp;oid=120399700&amp;loc=SL114874048-224260<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 810<br> -SubTopic 10<br> -Section 55<br> -Paragraph 4K<br> -URI http://asc.fasb.org/extlink&amp;oid=120409616&amp;loc=SL4591552-111686<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section 45<br> -Paragraph 1A<br> -Subparagraph (c)<br> -URI http://asc.fasb.org/extlink&amp;oid=121641772&amp;loc=SL7669619-108580<br><br>Reference 6: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 810<br> -SubTopic 10<br> -Section 45<br> -Paragraph 21<br> -URI http://asc.fasb.org/extlink&amp;oid=108774443&amp;loc=SL4613674-111683<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.5-03(23))<br> -URI http://asc.fasb.org/extlink&amp;oid=120395209&amp;loc=SL114868664-224227<br><br>Reference 8: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 810<br> -SubTopic 10<br> -Section 45<br> -Paragraph 20<br> -URI http://asc.fasb.org/extlink&amp;oid=108774443&amp;loc=SL4569643-111683<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ComprehensiveIncomeNetOfTaxAttributableToNoncontrollingInterest</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<td><strong> Balance Type:</strong></td>
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<td><strong> Period Type:</strong></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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount after tax of increase (decrease) in equity from transactions and other events and circumstances from net income and other comprehensive income. Excludes changes in equity resulting from investments by owners and distributions to owners.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 810<br> -SubTopic 10<br> -Section 55<br> -Paragraph 4K<br> -URI http://asc.fasb.org/extlink&amp;oid=120409616&amp;loc=SL4591552-111686<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section 45<br> -Paragraph 1A<br> -Subparagraph (c)<br> -URI http://asc.fasb.org/extlink&amp;oid=121641772&amp;loc=SL7669619-108580<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 944<br> -SubTopic 220<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-04(20))<br> -URI http://asc.fasb.org/extlink&amp;oid=120400993&amp;loc=SL114874131-224263<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 810<br> -SubTopic 10<br> -Section 45<br> -Paragraph 19<br> -URI http://asc.fasb.org/extlink&amp;oid=108774443&amp;loc=SL4569616-111683<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section 45<br> -Paragraph 1B<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=121641772&amp;loc=SL7669625-108580<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.5-03(22))<br> -URI http://asc.fasb.org/extlink&amp;oid=120395209&amp;loc=SL114868664-224227<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 942<br> -SubTopic 220<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-04(24))<br> -URI http://asc.fasb.org/extlink&amp;oid=120399700&amp;loc=SL114874048-224260<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ComprehensiveIncomeNetOfTaxIncludingPortionAttributableToNoncontrollingInterest</td>
</tr>
<tr>
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<tr>
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<td>xbrli:monetaryItemType</td>
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<tr>
<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_OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 830<br> -SubTopic 20<br> -Section 35<br> -Paragraph 3<br> -URI http://asc.fasb.org/extlink&amp;oid=121605123&amp;loc=d3e30304-110892<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 830<br> -SubTopic 10<br> -Section 45<br> -Paragraph 9<br> -URI http://asc.fasb.org/extlink&amp;oid=120253306&amp;loc=d3e28129-110885<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 830<br> -SubTopic 30<br> -Section 45<br> -Paragraph 12<br> -URI http://asc.fasb.org/extlink&amp;oid=118261656&amp;loc=d3e32022-110900<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section 45<br> -Paragraph 10A<br> -Subparagraph (a-c)<br> -URI http://asc.fasb.org/extlink&amp;oid=121641772&amp;loc=SL7669646-108580<br><br>Reference 5: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section 45<br> -Paragraph 11<br> -URI http://asc.fasb.org/extlink&amp;oid=121641772&amp;loc=d3e637-108580<br></p></div>
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">- Definition</a><div><p>Amount, after tax and before adjustment, of unrealized holding gain (loss) on investment in debt security measured at fair value with change in fair value recognized in other comprehensive income (available-for-sale). Excludes unrealized gain (loss) on investment in debt security measured at amortized cost (held-to-maturity) from transfer to available-for-sale.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section 45<br> -Paragraph 10A<br> -Subparagraph (e)<br> -URI http://asc.fasb.org/extlink&amp;oid=121641772&amp;loc=SL7669646-108580<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section 45<br> -Paragraph 11<br> -URI http://asc.fasb.org/extlink&amp;oid=121641772&amp;loc=d3e637-108580<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_OtherComprehensiveIncomeUnrealizedHoldingGainLossOnSecuritiesArisingDuringPeriodNetOfTax</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
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<td><strong> Data Type:</strong></td>
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<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The consolidated profit or loss for the period, net of income taxes, including the portion attributable to the noncontrolling interest.</p></div>
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<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
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<span style="display: none;">v3.20.4</span><table class="report" border="0" cellspacing="2" id="idm140142740060456">
<tr>
<th class="tl" colspan="1" rowspan="1"><div style="width: 200px;"><strong>CONSOLIDATED STATEMENTS OF STOCKHOLDERS' EQUITY - USD ($)<br> shares in Thousands, $ in Thousands</strong></div></th>
<th class="th"><div>Common Stock [Member]</div></th>
<th class="th"><div>Additional Paid In Capital [Member]</div></th>
<th class="th"><div>Accumulated Other Comprehensive Loss [Member]</div></th>
<th class="th"><div>Accumulated Deficit [Member]</div></th>
<th class="th"><div>Total Ionis Stockholders' Equity [Member]</div></th>
<th class="th"><div>Noncontrolling Interest in Akcea Therapeutics, Inc. [Member]</div></th>
<th class="th"><div>Total</div></th>
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<tr class="rc">
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<td class="nump">$ 125<span></span>
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<td class="nump">$ 1,553,681<span></span>
</td>
<td class="num">$ (31,759)<span></span>
</td>
<td class="num">$ (1,241,034)<span></span>
</td>
<td class="nump">$ 281,013<span></span>
</td>
<td class="nump">$ 84,267<span></span>
</td>
<td class="nump">$ 365,280<span></span>
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<tr class="rc">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_SharesIssued', window );">Balance (in shares) at Dec. 31, 2017</a></td>
<td class="nump">124,976<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>
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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>
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<td class="text">&#160;<span></span>
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<td class="nump">$ 0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">273,741<span></span>
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<td class="nump">273,741<span></span>
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<td class="nump">0<span></span>
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<td class="nump">273,741<span></span>
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<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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">(280)<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(280)<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(280)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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">23<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">23<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">23<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_StockIssuedDuringPeriodValueNewIssues', window );">Biogen stock purchase</a></td>
<td class="nump">$ 11<span></span>
</td>
<td class="nump">447,954<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">447,965<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">447,965<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_StockIssuedDuringPeriodSharesNewIssues', window );">Biogen Stock purchase (in shares)</a></td>
<td class="nump">11,502<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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">27,898<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">27,900<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">27,900<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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">1,451<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue', window );">Stock-based compensation expense</a></td>
<td class="nump">$ 0<span></span>
</td>
<td class="nump">131,312<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">131,312<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">131,312<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_MinorityInterestPeriodIncreaseDecrease', window );">Noncontrolling interest in Akcea Therapeutics, Inc.</a></td>
<td class="nump">0<span></span>
</td>
<td class="num">(113,595)<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(113,595)<span></span>
</td>
<td class="nump">54,814<span></span>
</td>
<td class="num">(58,781)<span></span>
</td>
</tr>
<tr class="rc">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest', window );">Balance at Dec. 31, 2018</a></td>
<td class="nump">$ 138<span></span>
</td>
<td class="nump">2,047,250<span></span>
</td>
<td class="num">(32,016)<span></span>
</td>
<td class="num">(967,293)<span></span>
</td>
<td class="nump">1,048,079<span></span>
</td>
<td class="nump">139,081<span></span>
</td>
<td class="nump">1,187,160<span></span>
</td>
</tr>
<tr class="rc">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_SharesIssued', window );">Balance (in shares) at Dec. 31, 2018</a></td>
<td class="nump">137,929<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward', window );"><strong>Increase (Decrease) in Stockholders' Equity [Roll Forward]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_NetIncomeLoss', window );">Net income (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="nump">294,146<span></span>
</td>
<td class="nump">294,146<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">294,146<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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">6,633<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">6,633<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">6,633<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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">93<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">93<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">93<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_StockIssuedDuringPeriodValueShareBasedCompensationGross', window );">Issuance of common stock in connection with employee stock plans</a></td>
<td class="nump">$ 3<span></span>
</td>
<td class="nump">119,654<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">119,657<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">119,657<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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">3,100<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>
<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="top.Show.showAR( this, 'defref_ions_AdjustmentsToAdditionalPaidInCapitalEquityComponentOfConvertibleDebtRedemption', window );">1 percent convertible senior notes retirement, equity portion, net of tax</a></td>
<td class="nump">$ 0<span></span>
</td>
<td class="num">(77,331)<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(77,331)<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(77,331)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AdjustmentsToAdditionalPaidInCapitalEquityComponentOfConvertibleDebt', window );">0.125 percent convertible senior notes, equity portion, net of issuance costs and tax</a></td>
<td class="nump">0<span></span>
</td>
<td class="nump">81,877<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">81,877<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">81,877<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AdjustmentsToAdditionalPaidInCapitalWarrantIssued', window );">Issuance of warrants</a></td>
<td class="nump">0<span></span>
</td>
<td class="nump">56,110<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">56,110<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">56,110<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AdjustmentsToAdditionalPaidInCapitalOther', window );">Purchase of note hedges, net of tax</a></td>
<td class="nump">0<span></span>
</td>
<td class="num">(85,860)<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(85,860)<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(85,860)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_StockRepurchasedAndRetiredDuringPeriodValue', window );">Repurchases and retirements of common stock</a></td>
<td class="num">$ (1)<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(34,387)<span></span>
</td>
<td class="num">(34,388)<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(34,388)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_StockRepurchasedAndRetiredDuringPeriodShares', window );">Repurchases and retirements of common stock (in shares)</a></td>
<td class="num">(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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue', window );">Stock-based compensation expense</a></td>
<td class="nump">$ 0<span></span>
</td>
<td class="nump">146,574<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">146,574<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">146,574<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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">(19,242)<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(19,242)<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(19,242)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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">(154)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_MinorityInterestPeriodIncreaseDecrease', window );">Noncontrolling interest in Akcea Therapeutics, Inc.</a></td>
<td class="nump">$ 0<span></span>
</td>
<td class="num">(65,254)<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(65,254)<span></span>
</td>
<td class="nump">74,372<span></span>
</td>
<td class="nump">9,118<span></span>
</td>
</tr>
<tr class="rc">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest', window );">Balance at Dec. 31, 2019</a></td>
<td class="nump">$ 140<span></span>
</td>
<td class="nump">2,203,778<span></span>
</td>
<td class="num">(25,290)<span></span>
</td>
<td class="num">(707,534)<span></span>
</td>
<td class="nump">1,471,094<span></span>
</td>
<td class="nump">213,453<span></span>
</td>
<td class="nump">1,684,547<span></span>
</td>
</tr>
<tr class="rc">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_SharesIssued', window );">Balance (in shares) at Dec. 31, 2019</a></td>
<td class="nump">140,340<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward', window );"><strong>Increase (Decrease) in Stockholders' Equity [Roll Forward]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_NetIncomeLoss', window );">Net income (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">(451,286)<span></span>
</td>
<td class="num">(451,286)<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(451,286)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent', window );">Change in unrealized gains (losses), net of tax</a></td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">3,729<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">3,729<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">3,729<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax', window );">Foreign currency translation</a></td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">617<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">617<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">617<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_StockIssuedDuringPeriodValueShareBasedCompensationGross', window );">Issuance of common stock in connection with employee stock plans</a></td>
<td class="nump">$ 1<span></span>
</td>
<td class="nump">52,033<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">52,034<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">52,034<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensation', window );">Issuance of common stock in connection with employee stock plans (in shares)</a></td>
<td class="nump">1,721<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_MinorityInterestDecreaseFromRedemptions', window );">Purchase of noncontrolling interest of Akcea Therapeutics, Inc., including cash payments for cancellation of Akcea Therapeutics, Inc. equity awards</a></td>
<td class="nump">$ 0<span></span>
</td>
<td class="num">(324,022)<span></span>
</td>
<td class="nump">301<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(323,721)<span></span>
</td>
<td class="num">(220,965)<span></span>
</td>
<td class="num">(544,686)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_StockRepurchasedAndRetiredDuringPeriodValue', window );">Repurchases and retirements of common stock</a></td>
<td class="num">$ (1)<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(90,548)<span></span>
</td>
<td class="num">(90,549)<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(90,549)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_StockRepurchasedAndRetiredDuringPeriodShares', window );">Repurchases and retirements of common stock (in shares)</a></td>
<td class="num">(1,478)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue', window );">Stock-based compensation expense</a></td>
<td class="nump">$ 0<span></span>
</td>
<td class="nump">230,117<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">230,117<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">230,117<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation', window );">Payments of tax withholdings related to vesting of employee stock awards and exercise of employee stock options</a></td>
<td class="nump">$ 0<span></span>
</td>
<td class="num">(13,410)<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(13,410)<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(13,410)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_SharesPaidForTaxWithholdingForShareBasedCompensation', window );">Payments of tax withholdings related to vesting of employee stock awards and exercise of employee stock options (in shares)</a></td>
<td class="num">(217)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_AdjustmentsToAdditionalPaidInCapitalDeferredTaxLiabilityAdjustment', window );">Deferred tax liability adjustment due to purchase of noncontrolling interest of Akcea Therapeutics, Inc.</a></td>
<td class="nump">$ 0<span></span>
</td>
<td class="nump">7,714<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">7,714<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">7,714<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_MinorityInterestPeriodIncreaseDecrease', window );">Noncontrolling interest in Akcea Therapeutics, Inc.</a></td>
<td class="nump">0<span></span>
</td>
<td class="num">(42,564)<span></span>
</td>
<td class="num">(428)<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(42,992)<span></span>
</td>
<td class="nump">7,512<span></span>
</td>
<td class="num">(35,480)<span></span>
</td>
</tr>
<tr class="rc">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest', window );">Balance at Dec. 31, 2020</a></td>
<td class="nump">$ 140<span></span>
</td>
<td class="nump">$ 2,113,646<span></span>
</td>
<td class="num">$ (21,071)<span></span>
</td>
<td class="num">$ (1,249,368)<span></span>
</td>
<td class="nump">$ 843,347<span></span>
</td>
<td class="nump">$ 0<span></span>
</td>
<td class="nump">$ 843,347<span></span>
</td>
</tr>
<tr class="rc">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_SharesIssued', window );">Balance (in shares) at Dec. 31, 2020</a></td>
<td class="nump">140,366<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_AdjustmentsToAdditionalPaidInCapitalDeferredTaxLiabilityAdjustment">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of increase (decrease) in additional paid in capital (APIC) due to deferred tax liability adjustment associated with the purchase of noncontrolling interest of Akcea Therapeutics, Inc.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_AdjustmentsToAdditionalPaidInCapitalDeferredTaxLiabilityAdjustment</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_AdjustmentsToAdditionalPaidInCapitalEquityComponentOfConvertibleDebtRedemption">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Adjustment to additional paid in capital resulting from the redemption of convertible debt instruments as two separate components - a debt component and an equity component.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_AdjustmentsToAdditionalPaidInCapitalEquityComponentOfConvertibleDebtRedemption</td>
</tr>
<tr>
<td style="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_AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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_AdjustmentsToAdditionalPaidInCapitalEquityComponentOfConvertibleDebt">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Adjustment to additional paid in capital resulting from the recognition of convertible debt instruments as two separate components - a debt component and an equity component. This bifurcation may result in a basis difference associated with the liability component that represents a temporary difference for purposes of applying accounting for income taxes. The initial recognition of deferred taxes for the tax effect of that temporary difference is as an adjustment to additional paid in capital.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 20<br> -Section 25<br> -Paragraph 22<br> -URI http://asc.fasb.org/extlink&amp;oid=51819886&amp;loc=SL6014347-161799<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AdjustmentsToAdditionalPaidInCapitalEquityComponentOfConvertibleDebt</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>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_AdjustmentsToAdditionalPaidInCapitalOther">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 20<br> -Section 55<br> -Paragraph 12<br> -URI http://asc.fasb.org/extlink&amp;oid=120383193&amp;loc=d3e11149-113907<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=120381028&amp;loc=d3e5047-113901<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 20<br> -Section 55<br> -Paragraph 13<br> -URI http://asc.fasb.org/extlink&amp;oid=120383193&amp;loc=d3e11178-113907<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 35<br> -Paragraph 2<br> -URI http://asc.fasb.org/extlink&amp;oid=121326096&amp;loc=d3e4534-113899<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 20<br> -Section 25<br> -Paragraph 2<br> -URI http://asc.fasb.org/extlink&amp;oid=109126253&amp;loc=d3e4724-112606<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 505<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -URI http://asc.fasb.org/extlink&amp;oid=109259400&amp;loc=d3e21463-112644<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 505<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.3-04)<br> -URI http://asc.fasb.org/extlink&amp;oid=120397183&amp;loc=d3e187085-122770<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_IncreaseDecreaseInStockholdersEquityRollForward</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_MinorityInterestDecreaseFromRedemptions">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Decrease in noncontrolling interest (for example, but not limited to, redeeming or purchasing the interests of noncontrolling shareholders, issuance of shares (interests) by the non-wholly owned subsidiary to the parent entity for other than cash, and a buyback of shares (interest) by the non-wholly owned subsidiary from the noncontrolling interests).</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 810<br> -SubTopic 10<br> -Section 45<br> -Paragraph 23<br> -URI http://asc.fasb.org/extlink&amp;oid=108774443&amp;loc=SL4569655-111683<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 810<br> -SubTopic 10<br> -Section 45<br> -Paragraph 24<br> -URI http://asc.fasb.org/extlink&amp;oid=108774443&amp;loc=SL4616395-111683<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 505<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.3-04)<br> -URI http://asc.fasb.org/extlink&amp;oid=120397183&amp;loc=d3e187085-122770<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_MinorityInterestDecreaseFromRedemptions</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_MinorityInterestPeriodIncreaseDecrease">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Net Increase or Decrease in balance of noncontrolling interest in the subsidiary during the reporting period.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 810<br> -SubTopic 10<br> -Section 45<br> -Paragraph 16<br> -URI http://asc.fasb.org/extlink&amp;oid=108774443&amp;loc=SL4568740-111683<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_MinorityInterestPeriodIncreaseDecrease</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_NetIncomeLoss">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount after tax and reclassification adjustments, of appreciation (loss) in value of unsold available-for-sale securities, attributable to parent entity. Excludes amounts related to other than temporary impairment (OTTI) loss.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 810<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1A<br> -Subparagraph (c)(3)<br> -URI http://asc.fasb.org/extlink&amp;oid=109239629&amp;loc=SL4573702-111684<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 810<br> -SubTopic 10<br> -Section 45<br> -Paragraph 19<br> -URI http://asc.fasb.org/extlink&amp;oid=108774443&amp;loc=SL4569616-111683<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 810<br> -SubTopic 10<br> -Section 45<br> -Paragraph 20<br> -URI http://asc.fasb.org/extlink&amp;oid=108774443&amp;loc=SL4569643-111683<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 830<br> -SubTopic 20<br> -Section 35<br> -Paragraph 3<br> -URI http://asc.fasb.org/extlink&amp;oid=121605123&amp;loc=d3e30304-110892<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 830<br> -SubTopic 10<br> -Section 45<br> -Paragraph 9<br> -URI http://asc.fasb.org/extlink&amp;oid=120253306&amp;loc=d3e28129-110885<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 830<br> -SubTopic 30<br> -Section 45<br> -Paragraph 12<br> -URI http://asc.fasb.org/extlink&amp;oid=118261656&amp;loc=d3e32022-110900<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section 45<br> -Paragraph 10A<br> -Subparagraph (a-c)<br> -URI http://asc.fasb.org/extlink&amp;oid=121641772&amp;loc=SL7669646-108580<br><br>Reference 5: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section 45<br> -Paragraph 11<br> -URI http://asc.fasb.org/extlink&amp;oid=121641772&amp;loc=d3e637-108580<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_SharesIssued">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 505<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -URI http://asc.fasb.org/extlink&amp;oid=109259400&amp;loc=d3e21463-112644<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_SharesIssued</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:sharesItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_SharesPaidForTaxWithholdingForShareBasedCompensation">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_SharesPaidForTaxWithholdingForShareBasedCompensation</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:sharesItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_StockIssuedDuringPeriodSharesNewIssues">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Number of new stock issued during the period.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(29))<br> -URI http://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 505<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -URI http://asc.fasb.org/extlink&amp;oid=109259400&amp;loc=d3e21463-112644<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 505<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.3-04)<br> -URI http://asc.fasb.org/extlink&amp;oid=120397183&amp;loc=d3e187085-122770<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(28))<br> -URI http://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_StockIssuedDuringPeriodSharesNewIssues</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:sharesItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensation">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 505<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -URI http://asc.fasb.org/extlink&amp;oid=109259400&amp;loc=d3e21463-112644<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 505<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.3-04)<br> -URI http://asc.fasb.org/extlink&amp;oid=120397183&amp;loc=d3e187085-122770<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(28))<br> -URI http://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(29))<br> -URI http://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>
</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_StockIssuedDuringPeriodValueNewIssues">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Equity impact of the value of new stock issued during the period. Includes shares issued in an initial public offering or a secondary public offering.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 505<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.3-04)<br> -URI http://asc.fasb.org/extlink&amp;oid=120397183&amp;loc=d3e187085-122770<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 505<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -URI http://asc.fasb.org/extlink&amp;oid=109259400&amp;loc=d3e21463-112644<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(29))<br> -URI http://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(28))<br> -URI http://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_StockIssuedDuringPeriodValueNewIssues</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>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_StockIssuedDuringPeriodValueShareBasedCompensationGross">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<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_StockRepurchasedAndRetiredDuringPeriodShares">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Number of shares that have been repurchased and retired during the period.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(28))<br> -URI http://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 505<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.3-04)<br> -URI http://asc.fasb.org/extlink&amp;oid=120397183&amp;loc=d3e187085-122770<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(29))<br> -URI http://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 505<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -URI http://asc.fasb.org/extlink&amp;oid=109259400&amp;loc=d3e21463-112644<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_StockRepurchasedAndRetiredDuringPeriodShares</td>
</tr>
<tr>
<td style="padding-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_StockRepurchasedAndRetiredDuringPeriodValue">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Equity impact of the value of stock that has been repurchased and retired during the period. The excess of the purchase price over par value can be charged against retained earnings (once the excess is fully allocated to additional paid in capital).</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(28))<br> -URI http://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(29))<br> -URI http://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 505<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -URI http://asc.fasb.org/extlink&amp;oid=109259400&amp;loc=d3e21463-112644<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 505<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.3-04)<br> -URI http://asc.fasb.org/extlink&amp;oid=120397183&amp;loc=d3e187085-122770<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_StockRepurchasedAndRetiredDuringPeriodValue</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>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_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of stockholders' equity (deficit), net of receivables from officers, directors, owners, and affiliates of the entity, attributable to both the parent and noncontrolling interests. Amount excludes temporary equity. Alternate caption for the concept is permanent equity.</p></div>
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http://asc.fasb.org/extlink&amp;oid=6450520&amp;loc=d3e32583-110901<br><br>Reference 21: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 65<br> -Paragraph 15<br> -Subparagraph (e)<br> -URI http://asc.fasb.org/extlink&amp;oid=121322162&amp;loc=SL121327923-165333<br><br>Reference 22: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 65<br> -Paragraph 8<br> -Subparagraph (d)(2)<br><br>Reference 23: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 65<br> -Paragraph 8<br> -Subparagraph (d)(3)<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest</td>
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<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>
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<head>
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<span style="display: none;">v3.20.4</span><table class="report" border="0" cellspacing="2" id="idm140142728115016">
<tr>
<th class="tl" colspan="1" rowspan="1"><div style="width: 200px;"><strong>CONSOLIDATED STATEMENTS OF STOCKHOLDERS' EQUITY (Parenthetical)<br></strong></div></th>
<th class="th"><div>Dec. 31, 2020</div></th>
<th class="th"><div>Dec. 31, 2019</div></th>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_DebtInstrumentInterestRateStatedPercentage', window );">Interest rate on convertible senior notes</a></td>
<td class="nump">1.00%<span></span>
</td>
<td class="nump">1.00%<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_DebtInstrumentInterestRateStatedPercentage', window );">Interest rate on convertible senior notes</a></td>
<td class="nump">0.125%<span></span>
</td>
<td class="nump">0.125%<span></span>
</td>
</tr>
</table>
<div style="display: none;">
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<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02.22(a)(1))<br> -URI http://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DebtInstrumentInterestRateStatedPercentage</td>
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<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<td><strong> Balance Type:</strong></td>
<td>na</td>
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<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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
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<td><strong> Balance Type:</strong></td>
<td>na</td>
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<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
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</table></div>
</div></td></tr>
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<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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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<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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<td><strong> Period Type:</strong></td>
<td></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_DebtInstrumentAxis=ions_ConvertibleSeniorNotes0125PercentMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes0125PercentMember</td>
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<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
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<td><strong> Data Type:</strong></td>
<td>na</td>
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<td><strong> Balance Type:</strong></td>
<td></td>
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<td><strong> Period Type:</strong></td>
<td></td>
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<TEXT>
<html>
<head>
<title></title>
<link rel="stylesheet" type="text/css" href="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;">v3.20.4</span><table class="report" border="0" cellspacing="2" id="idm140142814232056">
<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, 2020</div></th>
<th class="th"><div>Dec. 31, 2019</div></th>
<th class="th"><div>Dec. 31, 2018</div></th>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ProfitLoss', window );">Net income (loss)</a></td>
<td class="num">$ (486,766)<span></span>
</td>
<td class="nump">$ 303,262<span></span>
</td>
<td class="nump">$ 214,985<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AdjustmentsToReconcileNetIncomeLossToCashProvidedByUsedInOperatingActivitiesAbstract', window );"><strong>Adjustments to reconcile net income (loss) to net cash provided by 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="top.Show.showAR( this, 'defref_us-gaap_Depreciation', window );">Depreciation</a></td>
<td class="nump">13,365<span></span>
</td>
<td class="nump">12,540<span></span>
</td>
<td class="nump">10,706<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_OperatingLeaseRightOfUseAssetAmortizationExpense', window );">Amortization of right-of-use operating lease assets</a></td>
<td class="nump">1,731<span></span>
</td>
<td class="nump">1,542<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="top.Show.showAR( this, 'defref_us-gaap_AmortizationOfIntangibleAssets', window );">Amortization of patents</a></td>
<td class="nump">2,064<span></span>
</td>
<td class="nump">1,912<span></span>
</td>
<td class="nump">1,822<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AccretionAmortizationOfDiscountsAndPremiumsInvestments', window );">Amortization of premium (discount) on investments, net</a></td>
<td class="nump">11,521<span></span>
</td>
<td class="num">(7,485)<span></span>
</td>
<td class="num">(1,013)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AmortizationOfFinancingCosts', window );">Amortization of debt issuance costs</a></td>
<td class="nump">2,578<span></span>
</td>
<td class="nump">1,942<span></span>
</td>
<td class="nump">1,810<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AmortizationOfDebtDiscountPremium', window );">Amortization of convertible senior notes discount</a></td>
<td class="nump">36,157<span></span>
</td>
<td class="nump">37,338<span></span>
</td>
<td class="nump">33,363<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ShareBasedCompensation', window );">Stock-based compensation expense</a></td>
<td class="nump">230,117<span></span>
</td>
<td class="nump">146,574<span></span>
</td>
<td class="nump">131,312<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_GainsLossesOnExtinguishmentOfDebt', window );">Loss on early retirement of debt</a></td>
<td class="nump">0<span></span>
</td>
<td class="nump">21,865<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="top.Show.showAR( this, 'defref_us-gaap_GainLossOnInvestments', window );">(Gain) loss on investments</a></td>
<td class="num">(16,540)<span></span>
</td>
<td class="num">(192)<span></span>
</td>
<td class="nump">210<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_DeferredIncomeTaxesAndTaxCredits', window );">Deferred income taxes, including changes in valuation allowance</a></td>
<td class="nump">313,272<span></span>
</td>
<td class="num">(7,096)<span></span>
</td>
<td class="num">(290,516)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ImpairmentOfIntangibleAssetsFinitelived', window );">Non-cash losses related to patents</a></td>
<td class="nump">1,948<span></span>
</td>
<td class="nump">2,226<span></span>
</td>
<td class="nump">802<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="top.Show.showAR( this, 'defref_us-gaap_IncreaseDecreaseInContractWithCustomerAsset', window );">Contracts receivable</a></td>
<td class="num">(13,170)<span></span>
</td>
<td class="num">(47,674)<span></span>
</td>
<td class="nump">47,595<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_IncreaseDecreaseInInventories', window );">Inventories</a></td>
<td class="num">(1,261)<span></span>
</td>
<td class="num">(5,411)<span></span>
</td>
<td class="nump">1,400<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_IncreaseDecreaseInOtherOperatingAssets', window );">Other current and long-term assets</a></td>
<td class="num">(9,975)<span></span>
</td>
<td class="num">(44,659)<span></span>
</td>
<td class="num">(29,348)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_IncreaseDecreaseInIncomeTaxesReceivable', window );">Long-term income tax receivable</a></td>
<td class="nump">0<span></span>
</td>
<td class="nump">8,418<span></span>
</td>
<td class="num">(223)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_IncreaseDecreaseInAccountsPayable', window );">Accounts payable</a></td>
<td class="num">(2,755)<span></span>
</td>
<td class="num">(16,343)<span></span>
</td>
<td class="num">(655)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_IncreaseDecreaseInIncomeTaxesPayableNetOfIncomeTaxesReceivable', window );">Income taxes</a></td>
<td class="num">(31,279)<span></span>
</td>
<td class="nump">31,656<span></span>
</td>
<td class="num">(710)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_IncreaseDecreaseInOtherEmployeeRelatedLiabilities', window );">Accrued compensation</a></td>
<td class="nump">28,371<span></span>
</td>
<td class="nump">8,089<span></span>
</td>
<td class="nump">4,117<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_IncreaseDecreaseInAccruedLiabilitiesAndDeferredLiabilities', window );">Accrued liabilities and deferred rent</a></td>
<td class="nump">32,424<span></span>
</td>
<td class="nump">16,406<span></span>
</td>
<td class="num">(17,005)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_IncreaseDecreaseInContractWithCustomerLiability', window );">Deferred contract revenue</a></td>
<td class="num">(75,910)<span></span>
</td>
<td class="num">(119,283)<span></span>
</td>
<td class="nump">494,254<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_NetCashProvidedByUsedInOperatingActivities', window );">Net cash provided by operating activities</a></td>
<td class="nump">35,892<span></span>
</td>
<td class="nump">345,627<span></span>
</td>
<td class="nump">602,906<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_PaymentsToAcquireAvailableForSaleSecuritiesDebt', window );">Purchases of short-term investments</a></td>
<td class="num">(1,570,410)<span></span>
</td>
<td class="num">(1,946,726)<span></span>
</td>
<td class="num">(1,794,735)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ProceedsFromSaleAndMaturityOfAvailableForSaleSecurities', window );">Proceeds from the sale of short-term investments</a></td>
<td class="nump">1,885,935<span></span>
</td>
<td class="nump">1,951,734<span></span>
</td>
<td class="nump">882,824<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_PaymentsToAcquirePropertyPlantAndEquipment', window );">Purchases of property, plant and equipment</a></td>
<td class="num">(35,120)<span></span>
</td>
<td class="num">(30,905)<span></span>
</td>
<td class="num">(13,608)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_PaymentsToAcquireOtherProductiveAssets', window );">Acquisition of licenses and other assets, net</a></td>
<td class="num">(5,928)<span></span>
</td>
<td class="num">(5,377)<span></span>
</td>
<td class="num">(4,044)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_PaymentsToAcquireOtherInvestments', window );">Purchase of strategic investments</a></td>
<td class="nump">0<span></span>
</td>
<td class="num">(10,000)<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="top.Show.showAR( this, 'defref_us-gaap_NetCashProvidedByUsedInInvestingActivities', window );">Net cash provided by (used in) investing activities</a></td>
<td class="nump">274,477<span></span>
</td>
<td class="num">(41,274)<span></span>
</td>
<td class="num">(929,563)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="top.Show.showAR( this, 'defref_us-gaap_ProceedsFromIssuanceOfSharesUnderIncentiveAndShareBasedCompensationPlansIncludingStockOptions', window );">Proceeds from equity, net</a></td>
<td class="nump">52,036<span></span>
</td>
<td class="nump">119,657<span></span>
</td>
<td class="nump">27,900<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="num">(13,411)<span></span>
</td>
<td class="num">(19,242)<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="top.Show.showAR( this, 'defref_us-gaap_ProceedsFromConvertibleDebt', window );">Proceeds from the issuance of 0.125 percent convertible senior notes</a></td>
<td class="nump">0<span></span>
</td>
<td class="nump">109,500<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="top.Show.showAR( this, 'defref_us-gaap_PaymentsOfDebtIssuanceCosts', window );">0.125 percent convertible senior notes issuance costs</a></td>
<td class="nump">0<span></span>
</td>
<td class="num">(10,428)<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="top.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">56,110<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="top.Show.showAR( this, 'defref_us-gaap_PaymentsForHedgeFinancingActivities', window );">Purchase of note hedges</a></td>
<td class="nump">0<span></span>
</td>
<td class="num">(108,684)<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="top.Show.showAR( this, 'defref_us-gaap_PaymentsForRepurchaseOfCommonStock', window );">Repurchases and retirements of common stock</a></td>
<td class="num">(90,548)<span></span>
</td>
<td class="num">(34,392)<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="top.Show.showAR( this, 'defref_us-gaap_PaymentsToMinorityShareholders', window );">Purchase of noncontrolling interest of Akcea Therapeutics, Inc., including cash payments for cancellation of Akcea Therapeutics, Inc. equity awards</a></td>
<td class="num">(544,686)<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="top.Show.showAR( this, 'defref_us-gaap_RepaymentsOfLongTermLinesOfCredit', window );">Principal payments on line of credit</a></td>
<td class="nump">0<span></span>
</td>
<td class="num">(12,500)<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="top.Show.showAR( this, 'defref_us-gaap_ProceedsFromIssuanceOfCommonStock', window );">Proceeds from the issuance of common stock to Biogen</a></td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">447,965<span></span>
</td>
</tr>
<tr class="rou">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_NetCashProvidedByUsedInFinancingActivities', window );">Net cash (used in) provided by financing activities</a></td>
<td class="num">(596,609)<span></span>
</td>
<td class="nump">100,021<span></span>
</td>
<td class="nump">475,865<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_EffectOfExchangeRateOnCashAndCashEquivalents', window );">Effects of exchange rates on cash</a></td>
<td class="nump">617<span></span>
</td>
<td class="nump">93<span></span>
</td>
<td class="num">(18)<span></span>
</td>
</tr>
<tr class="rou">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect', window );">Net (decrease) increase in cash and cash equivalents</a></td>
<td class="num">(285,623)<span></span>
</td>
<td class="nump">404,467<span></span>
</td>
<td class="nump">149,190<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents', window );">Cash and cash equivalents at beginning of year</a></td>
<td class="nump">683,287<span></span>
</td>
<td class="nump">278,820<span></span>
</td>
<td class="nump">129,630<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents', window );">Cash and cash equivalents at end of year</a></td>
<td class="nump">397,664<span></span>
</td>
<td class="nump">683,287<span></span>
</td>
<td class="nump">278,820<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_InterestPaidNet', window );">Interest paid</a></td>
<td class="nump">6,247<span></span>
</td>
<td class="nump">9,870<span></span>
</td>
<td class="nump">9,592<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_IncomeTaxesPaidNet', window );">Income taxes paid</a></td>
<td class="nump">25,855<span></span>
</td>
<td class="nump">9,041<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="top.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="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RightOfUseAssetObtainedInExchangeForOperatingLeaseLiability', window );">Right-of-use assets obtained in exchange for lease liabilities</a></td>
<td class="nump">2,149<span></span>
</td>
<td class="nump">14,178<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="top.Show.showAR( this, 'defref_ions_NonCashCapitalAndPatentExpenditures', window );">Amounts accrued for capital and patent expenditures</a></td>
<td class="nump">4,059<span></span>
</td>
<td class="nump">3,126<span></span>
</td>
<td class="nump">4,428<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_CapitalExpendituresIncurredButNotYetPaid', window );">Purchases of property, plant and equipment included in long-term obligations</a></td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">3,350<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_NotesIssued1', window );">0.125 percent convertible senior notes principal issued related to our December 2019 debt exchange/issuance</a></td>
<td class="nump">0<span></span>
</td>
<td class="nump">439,326<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="top.Show.showAR( this, 'defref_us-gaap_NotesReduction', window );">1 percent convertible senior notes principal extinguished related to our December 2019 debt exchange</a></td>
<td class="nump">$ 0<span></span>
</td>
<td class="nump">$ 375,590<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_IncreaseDecreaseInAccruedLiabilitiesAndDeferredLiabilities">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The increase (decrease) during the reporting period in the aggregate amount of expenses incurred but not yet paid and the change during the period in carrying value for all deferred liabilities due within one year or operating cycle.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_IncreaseDecreaseInAccruedLiabilitiesAndDeferredLiabilities</td>
</tr>
<tr>
<td style="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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</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_us-gaap_AccretionAmortizationOfDiscountsAndPremiumsInvestments">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 28<br> -URI http://asc.fasb.org/extlink&amp;oid=121586364&amp;loc=d3e3602-108585<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of noncash expense included in interest expense to amortize debt discount and premium associated with the related debt instruments. Excludes amortization of financing costs. Alternate captions include noncash interest expense.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 835<br> -SubTopic 30<br> -Section 45<br> -Paragraph 1A<br> -URI http://asc.fasb.org/extlink&amp;oid=119993939&amp;loc=d3e28541-108399<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=121586364&amp;loc=d3e3602-108585<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.5-03.8)<br> -URI http://asc.fasb.org/extlink&amp;oid=120395209&amp;loc=SL114868664-224227<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AmortizationOfDebtDiscountPremium</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<tr>
<td><strong> Period Type:</strong></td>
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</tr>
</table></div>
</div></td></tr>
</table>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of amortization expense attributable to debt issuance costs.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=121586364&amp;loc=d3e3602-108585<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.5-03(8))<br> -URI http://asc.fasb.org/extlink&amp;oid=120395209&amp;loc=SL114868664-224227<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 835<br> -SubTopic 30<br> -Section 45<br> -Paragraph 3<br> -URI http://asc.fasb.org/extlink&amp;oid=119993939&amp;loc=d3e28555-108399<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>
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<td><strong> Data Type:</strong></td>
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<td><strong> Balance Type:</strong></td>
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</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=121586364&amp;loc=d3e3602-108585<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 350<br> -SubTopic 30<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (a)(2)<br> -URI http://asc.fasb.org/extlink&amp;oid=66006027&amp;loc=d3e16323-109275<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 350<br> -SubTopic 30<br> -Section 45<br> -Paragraph 2<br> -URI http://asc.fasb.org/extlink&amp;oid=6388964&amp;loc=d3e16225-109274<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>
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<tr>
<td><strong> Period Type:</strong></td>
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</tr>
</table></div>
</div></td></tr>
</table>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Future cash outflow to pay for purchases of fixed assets that have occurred.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 50<br> -Paragraph 5<br> -URI http://asc.fasb.org/extlink&amp;oid=121583591&amp;loc=d3e4332-108586<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 50<br> -Paragraph 4<br> -URI http://asc.fasb.org/extlink&amp;oid=121583591&amp;loc=d3e4313-108586<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 50<br> -Paragraph 3<br> -URI http://asc.fasb.org/extlink&amp;oid=121583591&amp;loc=d3e4304-108586<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_CapitalExpendituresIncurredButNotYetPaid</td>
</tr>
<tr>
<td style="padding-right: 4px;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_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 24<br> -URI http://asc.fasb.org/extlink&amp;oid=121586364&amp;loc=d3e3521-108585<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 4<br> -URI http://asc.fasb.org/extlink&amp;oid=121586364&amp;loc=d3e3044-108585<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 50<br> -Paragraph 8<br> -URI http://asc.fasb.org/extlink&amp;oid=121583591&amp;loc=SL98516268-108586<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 830<br> -SubTopic 230<br> -Section 45<br> -Paragraph 1<br> -URI http://asc.fasb.org/extlink&amp;oid=98513438&amp;loc=d3e33268-110906<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 24<br> -URI http://asc.fasb.org/extlink&amp;oid=121586364&amp;loc=d3e3521-108585<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>
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<td><strong> Data Type:</strong></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>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>
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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>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DeferredIncomeTaxesAndTaxCredits">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of deferred income tax expense (benefit) and income tax credits.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 28<br> -URI http://asc.fasb.org/extlink&amp;oid=121586364&amp;loc=d3e3602-108585<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DeferredIncomeTaxesAndTaxCredits</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 360<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=6391035&amp;loc=d3e2868-110229<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=121586364&amp;loc=d3e3602-108585<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>
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</tr>
<tr>
<td><strong> Data Type:</strong></td>
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</tr>
<tr>
<td><strong> Balance Type:</strong></td>
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</tr>
<tr>
<td><strong> Period Type:</strong></td>
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</tr>
</table></div>
</div></td></tr>
</table>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of increase (decrease) from the effect of exchange rate changes on cash and cash equivalent balances held in foreign currencies.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 830<br> -SubTopic 230<br> -Section 45<br> -Paragraph 1<br> -URI http://asc.fasb.org/extlink&amp;oid=98513438&amp;loc=d3e33268-110906<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_EffectOfExchangeRateOnCashAndCashEquivalents</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>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_GainLossOnInvestments">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of realized and unrealized gain (loss) on investment.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 320<br> -SubTopic 10<br> -Section 50<br> -Paragraph 10<br> -Subparagraph (c)<br> -URI http://asc.fasb.org/extlink&amp;oid=121645371&amp;loc=d3e27405-111563<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.5-03.7(c),9(a))<br> -URI http://asc.fasb.org/extlink&amp;oid=120395209&amp;loc=SL114868664-224227<br><br>Reference 3: http://www.xbrl.org/2003/role/recommendedDisclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=121586364&amp;loc=d3e3602-108585<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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_GainsLossesOnExtinguishmentOfDebt">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 50<br> -Section 40<br> -Paragraph 4<br> -URI http://asc.fasb.org/extlink&amp;oid=117329964&amp;loc=d3e12355-112629<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 50<br> -Section 40<br> -Paragraph 2<br> -URI http://asc.fasb.org/extlink&amp;oid=117329964&amp;loc=d3e12317-112629<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=121586364&amp;loc=d3e3602-108585<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=121586364&amp;loc=d3e3602-108585<br><br>Reference 2: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 350<br> -SubTopic 30<br> -Section 50<br> -Paragraph 3<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=66006027&amp;loc=d3e16373-109275<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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_IncomeTaxesPaidNet">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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, net of any cash received during the current period as refunds for the overpayment of taxes.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -URI http://asc.fasb.org/extlink&amp;oid=121583591&amp;loc=d3e4297-108586<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_IncomeTaxesPaidNet</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=121586364&amp;loc=d3e3602-108585<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=121586364&amp;loc=d3e3602-108585<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=121586364&amp;loc=d3e3602-108585<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=121586364&amp;loc=d3e3602-108585<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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_IncreaseDecreaseInIncomeTaxesReceivable">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The increase (decrease) during the reporting period in income taxes receivable, which represents the amount due from tax authorities for refunds of overpayments or recoveries of income taxes paid.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=121586364&amp;loc=d3e3602-108585<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_IncreaseDecreaseInIncomeTaxesReceivable</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>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_IncreaseDecreaseInInventories">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=121586364&amp;loc=d3e3602-108585<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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_IncreaseDecreaseInOtherEmployeeRelatedLiabilities">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=121586364&amp;loc=d3e3602-108585<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=121586364&amp;loc=d3e3602-108585<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -URI http://asc.fasb.org/extlink&amp;oid=121583591&amp;loc=d3e4297-108586<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 17<br> -Subparagraph (d)<br> -URI http://asc.fasb.org/extlink&amp;oid=121586364&amp;loc=d3e3367-108585<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 25<br> -Subparagraph (e)<br> -URI http://asc.fasb.org/extlink&amp;oid=121586364&amp;loc=d3e3536-108585<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 24<br> -URI http://asc.fasb.org/extlink&amp;oid=121586364&amp;loc=d3e3521-108585<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 24<br> -URI http://asc.fasb.org/extlink&amp;oid=121586364&amp;loc=d3e3521-108585<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 25<br> -URI http://asc.fasb.org/extlink&amp;oid=121586364&amp;loc=d3e3536-108585<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 24<br> -URI http://asc.fasb.org/extlink&amp;oid=121586364&amp;loc=d3e3521-108585<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 28<br> -URI http://asc.fasb.org/extlink&amp;oid=121586364&amp;loc=d3e3602-108585<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_NetCashProvidedByUsedInOperatingActivities</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_NetCashProvidedByUsedInOperatingActivitiesAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_NetCashProvidedByUsedInOperatingActivitiesAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_NotesIssued1">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The fair value of notes issued in noncash investing and financing activities.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 50<br> -Paragraph 4<br> -URI http://asc.fasb.org/extlink&amp;oid=121583591&amp;loc=d3e4313-108586<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 50<br> -Paragraph 5<br> -URI http://asc.fasb.org/extlink&amp;oid=121583591&amp;loc=d3e4332-108586<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 50<br> -Paragraph 3<br> -URI http://asc.fasb.org/extlink&amp;oid=121583591&amp;loc=d3e4304-108586<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_NotesIssued1</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>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_NotesReduction">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The value of notes retired (or transferred to another entity) in noncash investing or financing transactions.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 50<br> -Paragraph 5<br> -URI http://asc.fasb.org/extlink&amp;oid=121583591&amp;loc=d3e4332-108586<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 50<br> -Paragraph 3<br> -URI http://asc.fasb.org/extlink&amp;oid=121583591&amp;loc=d3e4304-108586<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 50<br> -Paragraph 4<br> -URI http://asc.fasb.org/extlink&amp;oid=121583591&amp;loc=d3e4313-108586<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_NotesReduction</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>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_OperatingLeaseRightOfUseAssetAmortizationExpense">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of amortization expense for right-of-use asset from operating lease.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=121586364&amp;loc=d3e3602-108585<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_OperatingLeaseRightOfUseAssetAmortizationExpense</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_PaymentsForHedgeFinancingActivities">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 15<br> -URI http://asc.fasb.org/extlink&amp;oid=121586364&amp;loc=d3e3291-108585<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 27<br> -URI http://asc.fasb.org/extlink&amp;oid=121586364&amp;loc=d3e3581-108585<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PaymentsForHedgeFinancingActivities</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_PaymentsForRepurchaseOfCommonStock">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The cash outflow to reacquire common stock during the period.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 15<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=121586364&amp;loc=d3e3291-108585<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PaymentsForRepurchaseOfCommonStock</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_PaymentsOfDebtIssuanceCosts">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 15<br> -Subparagraph (e)<br> -URI http://asc.fasb.org/extlink&amp;oid=121586364&amp;loc=d3e3291-108585<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PaymentsOfDebtIssuanceCosts</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_PaymentsRelatedToTaxWithholdingForShareBasedCompensation">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 15<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=121586364&amp;loc=d3e3291-108585<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 13<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=121586364&amp;loc=d3e3213-108585<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 11<br> -URI http://asc.fasb.org/extlink&amp;oid=121586364&amp;loc=d3e3151-108585<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 320<br> -SubTopic 10<br> -Section 45<br> -Paragraph 11<br> -URI http://asc.fasb.org/extlink&amp;oid=121553693&amp;loc=d3e26853-111562<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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_PaymentsToAcquireOtherInvestments">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 13<br> -URI http://asc.fasb.org/extlink&amp;oid=121586364&amp;loc=d3e3213-108585<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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_PaymentsToAcquireOtherProductiveAssets">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of cash outflow for the purchase of or improvements to tangible or intangible assets, used to produce goods or deliver services, classified as other.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 13<br> -Subparagraph (c)<br> -URI http://asc.fasb.org/extlink&amp;oid=121586364&amp;loc=d3e3213-108585<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PaymentsToAcquireOtherProductiveAssets</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 13<br> -Subparagraph (c)<br> -URI http://asc.fasb.org/extlink&amp;oid=121586364&amp;loc=d3e3213-108585<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PaymentsToAcquirePropertyPlantAndEquipment</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_PaymentsToMinorityShareholders">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of cash outflow to a noncontrolling interest. Includes, but not limited to, reduction of noncontrolling interest ownership. Excludes dividends paid to the noncontrolling interest.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 15<br> -URI http://asc.fasb.org/extlink&amp;oid=121586364&amp;loc=d3e3291-108585<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PaymentsToMinorityShareholders</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 14<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=121586364&amp;loc=d3e3255-108585<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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_ProceedsFromIssuanceOfCommonStock">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 14<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=121586364&amp;loc=d3e3255-108585<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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_ProceedsFromIssuanceOfSharesUnderIncentiveAndShareBasedCompensationPlansIncludingStockOptions">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2A<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=120381028&amp;loc=SL79508275-113901<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 14<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=121586364&amp;loc=d3e3255-108585<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 14<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=121586364&amp;loc=d3e3255-108585<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 11<br> -URI http://asc.fasb.org/extlink&amp;oid=121586364&amp;loc=d3e3151-108585<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 12<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=121586364&amp;loc=d3e3179-108585<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 320<br> -SubTopic 10<br> -Section 45<br> -Paragraph 11<br> -URI http://asc.fasb.org/extlink&amp;oid=121553693&amp;loc=d3e26853-111562<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>
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<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
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<tr>
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<tr>
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</div></td></tr>
</table>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The consolidated profit or loss for the period, net of income taxes, including the portion attributable to the noncontrolling interest.</p></div>
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-Name Accounting Standards Codification<br> -Topic 810<br> -SubTopic 10<br> -Section 45<br> -Paragraph 19<br> -URI http://asc.fasb.org/extlink&amp;oid=108774443&amp;loc=SL4569616-111683<br><br>Reference 18: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 323<br> -SubTopic 10<br> -Section 50<br> -Paragraph 3<br> -Subparagraph (c)<br> -URI http://asc.fasb.org/extlink&amp;oid=114001798&amp;loc=d3e33918-111571<br><br>Reference 19: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (f)<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e8933-108599<br><br>Reference 20: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 810<br> -SubTopic 10<br> -Section 55<br> -Paragraph 4K<br> -URI 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<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ProfitLoss</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
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<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>duration</td>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_RepaymentsOfLongTermLinesOfCredit">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The cash outflow for the settlement of obligation drawn from a contractual arrangement with the lender, including letter of credit, standby letter of credit and revolving credit arrangements, under which borrowings can be made up to a specific amount at any point in time with maturities due beyond one year or the operating cycle, if longer.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 15<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=121586364&amp;loc=d3e3291-108585<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_RepaymentsOfLongTermLinesOfCredit</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<td><strong> Data Type:</strong></td>
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<td><strong> Balance Type:</strong></td>
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<tr>
<td><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_RightOfUseAssetObtainedInExchangeForOperatingLeaseLiability">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 842<br> -SubTopic 20<br> -Section 55<br> -Paragraph 53<br> -URI http://asc.fasb.org/extlink&amp;oid=121568110&amp;loc=SL77918982-209971<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 842<br> -SubTopic 20<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (g)(2)<br> -URI http://asc.fasb.org/extlink&amp;oid=121609121&amp;loc=SL77918686-209980<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>
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<td><strong> Data Type:</strong></td>
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<tr>
<td><strong> Balance Type:</strong></td>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of noncash expense for share-based payment arrangement.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=121586364&amp;loc=d3e3602-108585<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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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<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
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<span style="display: none;">v3.20.4</span><table class="report" border="0" cellspacing="2" id="idm140142728155848">
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<th class="tl" colspan="1" rowspan="1"><div style="width: 200px;"><strong>CONSOLIDATED STATEMENTS OF CASH FLOWS (Parenthetical)<br></strong></div></th>
<th class="th"><div>Dec. 31, 2020</div></th>
<th class="th"><div>Dec. 31, 2019</div></th>
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<td class="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="top.Show.showAR( this, 'defref_us-gaap_DebtInstrumentInterestRateStatedPercentage', window );">Interest rate on convertible senior notes</a></td>
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<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.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="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02.22(a)(1))<br> -URI http://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br></p></div>
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<span style="display: none;">v3.20.4</span><table class="report" border="0" cellspacing="2" id="idm140142725216072">
<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>
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<tr><th class="th"><div>Dec. 31, 2020</div></th></tr>
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<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;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In our consolidated financial statements we included the accounts of Ionis Pharmaceuticals, Inc. and the consolidated results of our subsidiary, Akcea Therapeutics, Inc. and its wholly owned subsidiaries (&#8220;we&#8221;, &#8220;us&#8221; or &#8220;our&#8221;). We formed Akcea in December 2014. In July 2017, Akcea completed an initial public offering, or IPO. Prior to Akcea&#8217;s IPO in July 2017, we owned </span>100 percent<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> of Akcea. In October 2020, we acquired the shares of Akcea&#8217;s common stock we did not own. We will refer to this transaction as the Akcea Acquisition throughout the remainder of this document. </span>See Note 7, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Akcea Acquisition</span>, in the Notes to the Consolidated Financial Statements for further details.<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> We reflected changes in our ownership percentage in our financial statements as an adjustment to noncontrolling interest in the period the change occurred.</span></div>

<div><br/></div>

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> </span><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We incorporated in California on January 10, 1989. In conjunction with our IPO, we reorganized as a Delaware corporation in April 1991. We were organized principally to develop human therapeutic medicines using antisense technology. In December 2015, we changed our name from Isis Pharmaceuticals, Inc. to Ionis Pharmaceuticals, Inc.</div>

<div><br/></div>

<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Basic and Diluted Net Income (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 income (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 income (loss) per share by dividing the total net income (loss) attributable to our common stockholders 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;">The calculation of total net income (loss) attributable to our common stockholders for each year considered our net income (loss) for Ionis on a stand-alone basis plus our share of Akcea&#8217;s net income (loss) for the period. To calculate the portion of Akcea&#8217;s net income (loss) attributable to our ownership for each year, we multiplied Akcea&#8217;s income (loss) per share by the weighted average shares we owned in Akcea during the period. As a result of this calculation, our total net income (loss) available to Ionis common stockholders for the calculation of net income (loss) per share is different than net income (loss) attributable to Ionis Pharmaceuticals, Inc. common stockholders in our consolidated statements of operations for each 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;">Our basic net income (loss) per share was calculated as follows (in thousands, except per share amounts):</div>

<div><br/></div>

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  <tr>
    <td style="vertical-align: bottom; border-bottom: #000000 2px solid; white-space: nowrap;" valign="bottom"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Year Ended December 31, 2020</div></td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Weighted</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Average Shares</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Owned in Akcea</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Akcea</span>&#8217;<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">s</span></div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Net Loss</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Per Share</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Basic Net Loss</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Per Share</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Calculation</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Akcea&#8217;s net loss in the pre-acquisition period attributable to our ownership</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">77,095</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(1.45</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(111,775</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Akcea&#8217;s net loss in the post-acquisition period attributable to our ownership</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(85,987</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Akcea&#8217;s total net loss attributable to our ownership</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(197,762</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Ionis&#8217; stand-alone net loss</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(253,725</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net loss available to Ionis common stockholders</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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  <tr>
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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; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
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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; white-space: nowrap;" 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%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
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</table>

<div><br/></div>

<table cellpadding="0" cellspacing="0" id="z7190f4cfc9904c35afaf55ca55271bf2" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
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  <tr>
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    <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>
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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"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.49</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">34,073</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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    <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">&#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%; 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">&#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%; white-space: nowrap;" valign="bottom">&#160;</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; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">34,073</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: 64%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Ionis&#8217; stand-alone net income</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">262,490</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>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net income available to Ionis common stockholders</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times 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; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">296,563</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Weighted average shares outstanding</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">139,998</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: top; width: 64%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Basic net income per share</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" 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; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2.12</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
</table>

<div><br/></div>

<table cellpadding="0" cellspacing="0" id="zc4df006abbbb4d5b9a0a303fb389d2b3" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
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    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Weighted</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Average Shares</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Owned in Akcea</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
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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;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Basic Net Income</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Per Share</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Calculation</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Common shares</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>
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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"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(2.74</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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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: top; width: 64%; white-space: nowrap;" valign="bottom"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Akcea&#8217;s net loss attributable to our ownership</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">&#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%; 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">&#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%; white-space: nowrap;" valign="bottom">&#160;</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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    <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: 64%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Ionis&#8217; stand-alone net income</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">440,806</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: top; width: 64%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net income available to Ionis common stockholders</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times 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; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">276,868</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Weighted average shares outstanding</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">132,320</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: top; width: 64%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Basic net income per share</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2.09</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; font-style: italic;">Diluted net income 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 year ended December 31, 2020, we incurred a net loss; therefore, we did not include dilutive common equivalent shares in the computation of diluted net loss per share because the effect would have been anti-dilutive. Common stock from the following would have had an anti-dilutive effect on net loss per share:</div>

<div><br/></div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="za661525f8bef42ea9eb273beec8c3ffa" 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; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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;</span></div></td>
  </tr>
</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="zcb135ba690824483aa0fa909f89a6a2a" 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; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1 percent<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> convertible senior notes;</span></div></td>
  </tr>
</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="zd9638f50b7c74568a481c388188fcd9b" 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; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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" id="zbac81e814d3144cfb944e6b840054211" 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; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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; and</div></td>
  </tr>
</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="za8f44a91052a49768a8cab1258c98733" 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; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">For the years ended December 31, 2019 and 2018, we had net income available to Ionis common stockholders. As a result, we computed diluted net income per share using the weighted-average number of common shares and dilutive common equivalent shares outstanding during each period.</span> We calculated our diluted net income per share as follows <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(in thousands except per share amounts):</span></div>

<div><br/></div>

<table cellpadding="0" cellspacing="0" id="zbebb8966d0bf411b9c7f046d05640cb2" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td style="vertical-align: bottom; border-bottom: #000000 2px solid;" valign="bottom"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Year Ended December 31, 2019</div></td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Income</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(Numerator)</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Shares</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(Denominator)</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Per-Share</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Amount</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net income available to Ionis common stockholders</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">296,563</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>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
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<div><br/></div>

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    <td colspan="1" style="text-align: left; 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; 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%;" 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>
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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>
    <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;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" 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%; 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%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: 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>
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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="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
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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="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
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  <tr>
    <td style="vertical-align: top; width: 64%; padding-bottom: 4px;" 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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">276,868</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">134,056</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">2.07</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>

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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">For each year presented, the calculation excluded our convertible senior notes because the effect on diluted earnings per share was anti-dilutive.</div>

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

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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-decoration: underline;">Our Revenue Sources</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 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 in deferred revenue on our consolidated balance sheet.</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;">Commercial Revenue: SPINRAZA royalties and Licensing and other royalty revenue</div>

<div><br/></div>

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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We earn commercial revenue primarily in the form of royalty payments on net sales of SPINRAZA. We will also recognize as commercial revenue sales milestone payments and royalties we earn under our other partnerships.</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;">Commercial Revenue: Product sales, net</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 added product sales from TEGSEDI to our commercial revenue in the fourth quarter of 2018 and we added product sales from WAYLIVRA to our commercial revenue in the third quarter of 2019. </span>In the U.S., we distribute TEGSEDI through an exclusive distribution agreement with a third-party logistics company, or 3PL, that takes title to TEGSEDI. The 3PL is our sole customer in the U.S. The 3PL then distributes TEGSEDI to a specialty pharmacy and a specialty distributor, which we collectively refer to as wholesalers, who then distribute TEGSEDI to health care providers and patients.</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 Europe, through 2020 we sold TEGSEDI and WAYLIVRA to hospitals and pharmacies using 3PLs as distributors. Beginning in 2021, we are commercializing TEGSEDI and WAYLIVRA in Europe through a distribution agreement with Swedish Orphan Biovitrum AB, or Sobi, an international biopharmaceutical company that focuses on rare diseases. Under the terms of this agreement, we retained the marketing authorization for both medicines 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;">In Latin America beginning in 2020, we sold TEGSEDI and WAYLIVRA to our partner, PTC Therapeutics. Under our collaboration agreement with PTC, PTC is commercializing TEGSEDI and WAYLIVRA in Latin America and Caribbean countries.</div>

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<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Research and development revenue under collaborative agreements</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 often 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, research and development, or R&amp;D, services, and manufacturing services.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We provide details about our collaboration agreements in Note 6, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Collaborative Arrangements and Licensing Agreements.</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">&#160;</span>Under each collaboration note we discuss our specific revenue recognition conclusions, including our significant performance obligations under each 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;"><span style="text-decoration: underline;">Steps to Recognize Revenue</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;">We use a five-step process to determine the amount of revenue we should recognize and when we should recognize it. The five step process is as follows:</div>

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    <td style="width: 36pt;"/>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">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; font-weight: bold;">Identify the contract</div></td>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Accounting rules require us to first determine if we have a contract with our partner, including confirming that we have met each of the following criteria:</div>

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  <tr>
    <td style="width: 36pt;"/>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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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  <tr>
    <td style="width: 36pt;"/>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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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  <tr>
    <td style="width: 36pt;"/>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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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  <tr>
    <td style="width: 36pt;"/>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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 cellpadding="0" cellspacing="0" class="DSPFListTable" id="zca7ebdde125e410485d2be933fa84a5b" 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; align: right;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; font-style: italic;">2</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; font-style: italic;">.</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; font-weight: bold;">Identify the performance obligations</div></td>
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<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We next identify our performance obligations, which represent the distinct goods and services we are required to provide under the contract. We typically have only one performance obligation at the inception of a contract, which is to perform R&amp;D services.</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;">Often we enter into a collaboration agreement in which we provide our partner with an option to license a medicine in the future. We may also provide our partner with an option to request that we provide additional goods or services in the future, such as active pharmaceutical ingredient, or API. We evaluate whether these options are material rights at the inception of the agreement. If we determine an option is a material right, we will consider the option a separate performance obligation. Historically, we have concluded that the options we grant to license a medicine in the future or to provide additional goods and services as requested by our partner are not material rights because these items are contingent upon future events that may not occur and are not priced at a significant discount. When a partner exercises its option to license a medicine or requests additional goods or services, then we identify a new performance obligation for that item</span>.</div>

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<div 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" id="z89d2a19ad3fd4d87aa3b3cc055a6b623" 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; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">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; font-weight: bold;">Determine the transaction price</div></td>
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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;">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;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Milestone payments are our most common type of variable consideration. We recognize milestone payments using the most likely amount method because we will either receive the milestone payment or we will not, which makes the potential milestone payment a binary event. The most likely amount method requires us to determine the likelihood of earning the milestone payment. We include a milestone payment in the transaction price once it is probable we will achieve the milestone event. Most often, we do not consider our milestone payments probable until we or our partner achieve the milestone event because the majority of our milestone payments are contingent upon events that are not within our control and/ or are usually based on scientific progress which is inherently uncertain. For example, in the </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">fourth</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> quarter of </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">2020</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, we earned</span> a $20 million <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">milestone payment from AstraZeneca when AstraZeneca initiated a Phase </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">2</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">b study for ION</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">449</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, our medicine in development targeting PCSK</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">9</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> to lower LDL-cholesterol. We did not consider the milestone payment probable until AstraZeneca achieved the milestone event because advancing ION</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">449</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> was contingent on AstraZeneca initiating a Phase </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">2</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">b study and was not within our control. We recognized the milestone payment in full in the period the milestone event was achieved because we did not have any remaining performance obligations related to the milestone payment</span>.</div>

<div><br/></div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z33954e5741c04959a455f20a29c4e558" 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; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">4.</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; font-weight: bold;">Allocate the transaction price</div></td>
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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;">Next, we allocate the transaction price to each of our performance obligations. When we have to allocate the transaction price to more than </span>one<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> performance obligation, we make estimates of the relative stand-alone selling price of each performance obligation because we do not typically sell our goods or services on a stand-alone basis. We then allocate the transaction price to each performance obligation based on the relative stand-alone selling price. We do not reallocate the transaction price after the start of an agreement to reflect subsequent changes in stand-alone selling prices.</span></div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We may engage a </span>third<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> party, independent valuation specialist to assist us with determining a stand-alone selling price for collaborations in which we deliver a license at the start of an agreement. We estimate the stand-alone selling price of these licenses using valuation methodologies, such as the relief from royalty method. Under this method, we estimate the amount of income, net of taxes, for the license. We then discount the projected income to present value. The significant inputs we use to determine the projected income of a license could include</span>:</div>

<div><br/></div>

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  <tr>
    <td style="width: 36pt;"/>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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>
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<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z10d63e5de2314c06ad22cc7840776d39" 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; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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" id="zba714425a66248a085047d1335e5f538" 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; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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" id="zbd24a106c9494a478e217043fc30b768" 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; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Expenses we expect to incur;</div></td>
  </tr>
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<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z77f6cf0e489e4770a51c02ff69b03c42" 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; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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" id="z55a0f09a57a440e78616543b799da651" 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; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="zb8283a4050434163907eb1ceed915b35" 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; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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 number of internal hours we estimate we will spend performing these services;</div></td>
  </tr>
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    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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 cellpadding="0" cellspacing="0" class="DSPFListTable" id="z00a44e034e0c47d3bd2e75356a388f81" 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; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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 cellpadding="0" cellspacing="0" class="DSPFListTable" id="z3ae90bb9080943f2b46aad96c46d875e" 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; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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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<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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<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="ze208c18727bc49289f50b3daf6d37408" 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; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">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; font-weight: bold;">Recognize revenue</div></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;">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 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;">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.</span> Refer to Note 6, <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 the cumulative catch up adjustment we made.</div>

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<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following are examples of when we typically recognize revenue based on the types of payments we receive.</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="text-decoration: underline;">Commercial Revenue: SPINRAZA royalties and Licensing and other royalty revenue</span></div>

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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We recognize royalty revenue, including royalties from SPINRAZA sales, in the period in which the counterparty sells the related product and recognizes the related revenue, which in certain cases may require us to estimate our royalty revenue</span>.</div>

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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><span style="text-decoration: underline;">Commercial Revenue: Product sales, net</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 recognize product sales in the period when our customer obtains control of our products, which occurs at a point in time upon transfer of title to the customer. We classify payments to customers or other parties in the distribution channel for services that are distinct and priced at fair value as selling, general and administrative, or SG&amp;A, expenses in our consolidated statements of operations. Otherwise, payments to customers or other parties in the distribution channel that do not meet those criteria are classified as a reduction of revenue, as discussed further below. We exclude from revenues taxes collected from customers relating to product sales and remitted to governmental authorities</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;">Reserves for Product sales</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 record product sales at our net sales price, or transaction price. We include in our transaction price estimated reserves for discounts, returns, chargebacks, rebates and other allowances that we offer within contracts between us and our customers, wholesalers, health care providers and other indirect customers. We estimate our reserves using the amounts we have earned or what we can claim on the associated sales. We classify our reserves as a reduction of accounts receivable when we are not required to make a payment or as a current liability when we are required to make a payment. In certain cases, our estimates include a range of possible outcomes that are probability weighted for relevant factors such as our historical experience, current contractual and statutory requirements, specific known market events and trends, industry data and forecasted customer buying and payment patterns. Overall, our reserves reflect our best estimates under the terms of our respective contracts. When calculating our reserves and related product sales, we only recognize amounts to the extent that we consider it probable that we would not have to reverse in a future period a significant amount of the cumulative sales we previously recognized. The actual amounts we receive may ultimately differ from our reserve estimates. If actual amounts in the future vary from our estimates, we will adjust these estimates, which would affect our net product sales in the respective period</span>.</div>

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<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following are the components of variable consideration related to product sales:</div>

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<div style="text-align: justify; margin-left: 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;">Chargebacks: </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In the U.S., we estimate obligations resulting from contractual commitments with the government and other entities to sell products to qualified healthcare providers at prices lower than the list prices charged to our U.S. customer. Our U.S. customer charges us for the difference between what it pays for the product and the selling price to the qualified healthcare providers. We also estimate the amount of chargebacks related to our estimated product remaining in the distribution channel at the end of the reporting period that we expect our customer to sell to healthcare providers in future periods. We record these reserves as a reduction to contracts receivable on our consolidated balance sheet</span>.</div>

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<div style="text-align: justify; margin-left: 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;">Government rebates</span><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;">We are subject to discount obligations under government programs, including Medicaid and Medicare programs in the U.S. and we record reserves for government rebates based on statutory discount rates and estimated utilization. We estimate Medicaid and Medicare rebates based on a range of possible outcomes that are probability weighted for the estimated payer mix. We record these reserves as an accrued liability on our consolidated balance sheet with a corresponding offset reducing our product sales in the same period we recognize the related sale. For Medicare, we also estimate the number of patients in the prescription drug coverage gap for whom we will owe an additional liability under the Medicare Part D program. On a quarterly basis, we update our estimates and record any adjustments in the period that we identify the adjustments</span>.</div>

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<div style="text-align: justify; margin-left: 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;">Managed care rebates: </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We are subject to rebates in connection with agreements with certain contracted commercial payers. We record these rebates as a liability on our consolidated balance sheet in the same period we recognize the related revenue. We estimate our managed care rebates based on our estimated payer mix and the applicable contractual rebate rate</span>.</div>

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<div style="text-align: justify; margin-left: 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;">Trade discounts: </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We provide customary invoice discounts on product sales to our U.S. customer for prompt payment. We record this discount as a reduction of product sales in the period in which we recognize the related product revenue</span>.</div>

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<div style="text-align: justify; margin-left: 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;">Distribution services</span>: <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We receive and pay for various distribution services from our U.S. and European customers (prior to our agreement with Sobi) and wholesalers in the U.S. We classify the costs for services we receive that are either not distinct from the sale of the product or for which we cannot reasonably estimate the fair value as a reduction of product sales. To the extent that the services we receive are distinct from the sale of the product, we classify the costs for such services as SG&amp;A expenses.</span></div>

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<div style="text-align: justify; margin-left: 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;">Product returns: </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Our U.S. customer has return rights and the wholesalers have limited return rights primarily related to the product&#8217;s expiration date. We estimate the amount of product sales that our customer may return. We record our return estimate as an accrued refund liability on our consolidated balance sheet with a corresponding offset reducing our product sales in the same period we recognize the related sale. Based on our distribution model for product sales, contractual inventory limits with our customer and wholesalers and the price of the product, we have had minimal returns to date and we believe we will continue to have minimal returns in the U.S. Our European customers generally only take title to the product after they receive an order and therefore they do not maintain excess inventory levels of our products. Accordingly, we have limited return risk in Europe and we do not estimate returns in Europe</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;"><span style="text-decoration: underline;">Research and development revenue under collaboration agreements:</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;"><span style="text-decoration: underline;">Upfront payments</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;">When we enter into a collaboration agreement with 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. For example, under our collaboration agreement with Roche to</span><span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> develop IONIS-FB-L</span><sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> for the treatment of complement-mediated diseases, we received a $</span>75<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million upfront payment in the fourth quarter of 2018. We allocated the upfront payment to our single performance obligation, R&amp;D services. We are amortizing the $</span>75<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million upfront payment using an input method over the estimated period of time we are providing 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; font-style: italic;"><span style="text-decoration: underline;">Milestone payments</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 are required to include additional consideration in the transaction price when it is probable. We typically include milestone payments for R&amp;D services in the transaction price when they are achieved. We include these milestone payments when they are achieved because typically there is considerable uncertainty in the research and development processes that trigger these payments. Similarly, we include approval milestone payments in the transaction price once the medicine is approved by the applicable regulatory agency. We will recognize sales-based milestone payments in the period in which we achieve the milestone under the sales-based royalty exception allowed under accounting rules.</div>

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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We recognize milestone payments that relate to an ongoing performance obligation over our period of performance. For example, in the </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">fourth</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> quarter of </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">2020</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, we achieved a</span> $7.5&#160;<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">million milestone payment from Biogen when we advanced</span>&#160;<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">a </span>target under our 2018 strategic collaboration.<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> We added this payment to the transaction price and allocated it to our R&amp;D services performance obligation. We are recognizing revenue related to this milestone payment over our estimated period of performance</span>.</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. For example, in the third quarter of 2020, we recognized $18 million in milestone payments when Biogen initiated a Phase 1/2 trial for <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">ION464, our medicine in development targeting alpha-synuclein to treat patients with multiple system atrophy</span>. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We concluded that the milestone payments were not related to our R&amp;D services performance obligation. Therefore, we recognized the milestone payments in full in the third quarter of 2020.</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;"><span style="text-decoration: underline;">License fees</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 generally recognize as revenue the total amount we determine to be the relative stand-alone selling price of a license when we deliver the license to our partner. This is because our partner has full use of the license and we do not have any additional performance obligations related to the license after delivery. For example, in the </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">fourth</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> quarter of </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">2020</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, we earned a</span> $30&#160;<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">million license fee from AstraZeneca when AstraZeneca licensed ION</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">455</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, an investigational medicine in development to treat nonalcoholic steatohepatitis, or 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; font-style: italic;"><span style="text-decoration: underline;">Sublicense fees</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 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>For example, in the fourth quarter of 2020, we earned a $41.2 million sublicense fee from Alnylam Pharmaceuticals for its sublicense of our technology to Sanofi Genzyme.</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;">Amendments to Agreements</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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<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="zc5f99d759c1848d881070e04e6c73535" 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; align: right; 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 cellpadding="0" cellspacing="0" class="DSPFListTable" id="z64fa57d8d257481ab6fc670c67d5e2dc" 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; align: right; 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 at a stand-alone selling price.</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 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 adjustment.</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;">For example, in May 2015, we entered into an exclusive license agreement with Bayer to develop and commercialize IONIS-FXI</span><sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> for the prevention of thrombosis. As part of the agreement, Bayer paid us a $</span>100<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million upfront payment. At the onset of the agreement, we were responsible for completing a Phase 2 study of IONIS-FXI</span><sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> in people with end-stage renal disease on hemodialysis and for providing an initial supply of API. In February 2017, we amended our agreement with Bayer to advance IONIS-FXI</span><sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> and to initiate development of IONIS-FXI-L</span><sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, which Bayer licensed. As part of the 2017 amendment, Bayer paid us $</span>75<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million. We are also eligible to receive milestone payments and tiered royalties on gross margins of IONIS-FXI</span><sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> and IONIS-FXI-L</span><sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. Under the 2017 amendment, we concluded we had a new agreement with </span>three<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> performance obligations. These performance obligations were to deliver the license of IONIS-FXI-L</span><sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, to provide R&amp;D services and to deliver API. We allocated the $</span>75<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million transaction price to these performance obligations. Refer to Note 6, </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Collaborative Arrangements and Licensing Agreements</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, </span>in our audited financial statements included in our Annual Report on Form 10-K for the year ended December 31, 2019 <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">for further discussion of the Bayer 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;">Multiple agreements</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;">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>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z4eb4c38c616c425ca052b7ee9921b301" 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; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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" id="z791c1b1e598245bfadb2be27fb53a91f" 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; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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" id="zca4b2c0359fd49008d64fab4cf31367c" 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; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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;">For example, in the second quarter of 2018, we entered into two separate agreements with Biogen at the same time: <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">a new strategic neurology collaboration agreement and a stock purchase agreement, or SPA. We evaluated the Biogen agreements to determine whether we should treat the agreements separately or combine them. We considered that the agreements were negotiated concurrently and in contemplation of </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">one</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> another. Based on these facts and circumstances, we concluded that we should evaluate the provisions of the agreements on a combined basis</span><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: 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: -54pt; margin-left: 54pt; 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 on our consolidated balance sheet.</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 on our consolidated balance sheet.</span> During the years ended December 31, 2020 and 2019, we recognized $100.4 million and $159.5 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 Products 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;">Our cost of products sold includes 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 products sold. Prior to obtaining regulatory approval of TEGSEDI in July 2018 and WAYLIVRA in May 2019, we expensed as research and development expenses a significant portion of the costs we incurred to produce the initial commercial launch supply for each medicine.</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;">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 and development expenses include wages, benefits, facilities, supplies, external services, clinical trial and manufacturing costs and other expenses that are directly related to our research and development operations. We expense research and development costs as we incur them. When we make payments for research and development services prior to the services being rendered, we record those amounts as prepaid assets on our consolidated balance sheet and we expense them as the services are provided. For the years ended December 31, 2020, 2019 and 2018, research and development expenses were $531.0 million, $461.5 million and $411.9 million, respectively. A portion of the costs included in research and development expenses are costs associated with our partner agreements. For the years ended December 31, 2020, 2019 and 2018, research and development costs of approximately $49.8 million, $83.2 million and $58.7 million, respectively, were related to our partner 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 capitalize costs consisting principally of outside legal costs and filing fees related to obtaining patents. We amortize patent costs over the useful life of the patent, beginning with the date the U.S. Patent and Trademark Office, or foreign equivalent, issues the patent. The weighted average remaining amortizable life of our issued patents was 10.3 years at December 31, 2020.</div>

<div><br/></div>

<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 cost of our patents capitalized on our consolidated balance sheet at December 31, 2020 and 2019 was $37.0 million and $34.0 million, respectively. Accumulated amortization related to patents was $9.1 million and $8.3 million at December 31, 2020 and 2019, 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;">Based on our existing patents, we estimate amortization expense related to patents in each of the next five years to be the following:</div>

<div><br/></div>

<table cellpadding="0" cellspacing="0" id="z1566f0aad503425294fc597dc5e10f73" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td style="vertical-align: bottom; border-bottom: #000000 2px solid;" valign="bottom"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Year Ending December 31,</div></td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Amortization</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(in millions)</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;">2021</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2.1</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 88%;" valign="bottom"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2022</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">2.0</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; 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;">2023</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1.9</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 88%;" valign="bottom"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2024</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">1.7</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: 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;">2025</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1.6</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
</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 review our capitalized patent costs regularly to ensure that they include costs for patents and patent applications that have future value. When we identify patents and patent applications that we are not actively pursuing, we write off any associated costs. In 2020, 2019 and 2018, patent expenses were $4.1 million, $4.2 million and $2.6 million, respectively, and included non-cash charges related to the write-down of our patent costs to their estimated net realizable values of $1.9 million, $2.2 million and $0.8 million, respectively.</div>

<div><br/></div>

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

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our accrued liabilities consisted of the following (in thousands):</div>

<div><br/></div>

<table cellpadding="0" cellspacing="0" id="zc442150657ce4320af53f69853dbac04" 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"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/></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;">2020</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;">2019</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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">39,477</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">24,461</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;">8,264</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10,289</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;">11,559</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6,020</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;">30,861</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;">25,999</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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">90,161</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">66,769</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
</table>

<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br/></div>

<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Noncontrolling Interest in Akcea Therapeutics, Inc.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Since Akcea&#8217;s IPO in July 2017 and prior to the Akcea Acquisition in October 2020, the shares of Akcea&#8217;s common stock third parties owned represented an interest in Akcea&#8217;s equity that we did not control. During this period our ownership ranged from </span>68 percent<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> to </span>77 percent<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. However, as we maintained overall control of Akcea through our voting interest, we reflected the assets, liabilities and results of operations of Akcea in our consolidated financial statements. Since Akcea&#8217;s IPO in July 2017 and through the closing of the Akcea Acquisition, we reflected the noncontrolling interest attributable to other owners of Akcea&#8217;s common stock on a separate line on our statement of operations and a separate line within stockholders&#8217; equity in our consolidated balance sheet. In addition, through the closing of the Akcea Acquisition, we recorded a noncontrolling interest adjustment to account for the stock options Akcea granted, which if exercised, would have diluted our ownership in Akcea. This adjustment was a reclassification within stockholders&#8217; equity from additional paid-in capital to noncontrolling interest in Akcea equal to the amount of stock-based compensation expense Akcea had recognized. Additionally, w</span>e reflected changes in our ownership percentage in our financial statements as an adjustment to noncontrolling interest in the period the change occurred.</div>

<div><br/></div>

<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">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;">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 statement of operations. We use the specific identification method to determine the cost of securities sold.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We also have equity investments of less than 20 percent ownership in publicly and privately held biotechnology companies that we received as part of a technology license or partner agreement. At December 31, 2020, we held equity investments in two publicly held companies, ProQR Therapeutics N.V., or ProQR, and Antisense Therapeutics Limited, or ATL. We also held equity investments in seven privately-held companies, Aro Biotherapeutics, Atlantic Pharmaceuticals Limited, Dynacure SAS, Empirico, Inc., Flamingo Therapeutics BV, Seventh Sense Biosystems and Suzhou-Ribo Life Science Co, Ltd.</div>

<div><br/></div>

<div 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 statement of operations. We account for our equity investments in privately held companies at their cost minus impairments, plus or minus changes resulting from observable price changes in orderly transactions for the identical or similar investment of the same issuer. For example, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">during the second and fourth quarters of 2020, we revalued our investments in </span>three<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> privately held companies, Dynacure, Suzhou-Ribo and Aro Biotherapeutics because the companies sold additional equity securities that were similar to the equity we own. These observable price changes resulted in us recognizing a $</span>6.3<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million gain on our investment in Dynacure, a $</span>3.0<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million gain on our investment in Suzhou-Ribo and a $</span>5.5<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million gain on our investment in Aro Biotherapeutics in our consolidated statement of operations during 2020 because the sales were at higher prices compared to our recorded value.</span></div>

<div><br/></div>

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

<div><br/></div>

<div 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 on our consolidated balance sheet 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.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We obtained the first regulatory approval for TEGSEDI in July 2018 and for WAYLIVRA in May 2019. At December 31, 2020, our physical inventory for TEGSEDI and WAYLIVRA included API that we produced prior to when we obtained regulatory approval. As such, this API has no cost basis as we had previously expensed the costs as R&amp;D expenses.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We 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. We recorded an <span style="-sec-ix-hidden:Fact_b86d72920caa47448f2abd7be8e5c180"><span style="-sec-ix-hidden:Fact_1261d93c836d4d94bba4bd8c45f1e569">insignificant</span></span> amount of inventory write-offs during the years ended December 31, 2020 and 2019. We did not record any inventory write-offs for the year ended December 31, 2018.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our inventory consisted of the following (in thousands):</div>

<div><br/></div>

<table cellpadding="0" cellspacing="0" id="z420cf186c4154a629acd33b8e4e537ba" 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"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/></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;">2020</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;">2019</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Raw materials:</div></td>
    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: justify; text-indent: -9pt; margin-left: 19.4pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Raw materials- clinical</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">9,206</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">9,363</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;">7,502</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;">6,520</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;">16,708</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;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">15,883</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 76%;" valign="bottom"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Work in process</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2,252</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;">2,039</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;">3,005</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;">258</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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">21,965</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">18,180</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
</table>

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

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

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We carry our property, plant and equipment at cost and depreciate it on the straight-line method over its estimated useful life, which consists of the following (in thousands):</div>

<div><br/></div>

<table cellpadding="0" cellspacing="0" id="z0d198c5954a847b59f5bfeab5aaeb505" 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"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/></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 Useful Lives</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">December 31,</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(in years)</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2020</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;">2019</div></td>
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  <tr>
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    <td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>
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  <tr>
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    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>
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  <tr>
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  <tr>
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    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>
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  <tr>
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  <tr>
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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="vertical-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%; 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>
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  <tr>
    <td style="vertical-align: bottom; width: 64%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
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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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  </tr>
  <tr>
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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%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
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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>
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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>
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  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 64%; padding-bottom: 4px;" valign="bottom"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#160;Total</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>
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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>
</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 depreciate our leasehold improvements using the shorter of the estimated useful life or remaining lease term.</div>

<div><br/></div>

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> </span><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We have estimated the fair value of our financial instruments. The amounts reported for cash, accounts receivable, accounts payable and accrued expenses approximate the fair value because of their short maturities. We report our investment securities at their estimated fair value based on quoted market prices for identical or similar instruments.</div>

<div><br/></div>

<div style="text-align: 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 on our consolidated balance sheet 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 concluded we were reasonably certain that we will 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 current leases do not provide an interest rate implicit in the lease, we used our incremental borrowing rate, based on the information available on the date we adopted Topic 842 (January 2019), 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. 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;">Long-Lived Assets</div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> </span><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We evaluate long-lived assets, which include property, plant and equipment and patent costs, 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. We recorded charges of $1.9 million, $2.2 million and $0.8 million for the years ended December 31, 2020, 2019 and 2018, respectively, related to the write-down of patents.</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;">The preparation of consolidated financial statements in conformity with accounting principles generally accepted in the U.S. requires management to make estimates and assumptions that affect the amounts reported in the consolidated financial statements and accompanying notes. Actual results could differ from those estimates.</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, 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 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. We estimate the expected term of options granted based on 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;">We recognize compensation expense for option awards and RSUs 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;">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 vest annually over a four-year period. RSUs granted after June 2020 to our board of directors vest annually.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">See Note 4, <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;">Accumulated Other Comprehensive Loss</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Accumulated other comprehensive loss is comprised of unrealized gains and losses on investments, net of taxes and currency translation adjustments. The following table summarizes changes in accumulated other comprehensive loss for the years ended December 31, </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">2020</span><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;">2019</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> and </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">2018</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> (in thousands):</span></div>

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

<table cellpadding="0" cellspacing="0" id="z0f84e575a1a8436991d62963b2899dd6" 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"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/></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;">2020</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;">2019</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;">2018</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Beginning balance accumulated other comprehensive loss</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(25,290</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(32,016</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;">(31,759</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 64%;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Unrealized gains (losses) on securities, net of tax (1)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3,729</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6,633</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;">(280</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: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Currency translation adjustment</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">617</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">93</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-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>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 64%; padding-bottom: 2px;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Adjustments to other comprehensive loss from purchase of noncontrolling interest of Akcea Therapeutics, Inc.</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(127</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <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: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net other comprehensive loss for the period</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4,219</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; 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;">6,726</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;">(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"><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: 4px;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Ending balance accumulated other comprehensive loss</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(21,071</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(25,290</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(32,016</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
</table>

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

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z9ecfa3f5cf504526a0786f25593849bf" 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; 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; text-indent: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We did not have tax expense included in our other comprehensive loss for the year ended December 31, 2020. For the years ended December 31, 2019 and 2018, we had a tax benefit $1.4 million and $0.3 million included in other comprehensive loss respectively.&#160;</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;">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;">At issuance, we accounted for our convertible debt instruments, including our 0.125 percent senior convertible notes, or 0.125% Notes, and 1 percent senior convertible notes, or 1% Notes, that may be settled in cash upon conversion (including partial cash settlement) by separating the liability and equity components of the instruments in a manner that reflects our nonconvertible debt borrowing rate on the date the notes were issued. In reviewing debt issuances, we were not able to identify any comparable companies that issued non-convertible debt instruments at the time of the issuance of the convertible notes. Therefore, we estimated the fair value of the liability component of our notes by using assumptions that market participants would use in pricing a debt instrument, including market interest rates, credit standing, yield curves and volatilities.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We assigned a value to the debt component of our convertible notes equal to the estimated fair value of similar debt instruments without the conversion feature, which resulted in us recording our debt at a discount. We are amortizing our debt issuance costs and debt discount over the life of the convertible notes as additional non-cash interest expense utilizing the effective interest method. For additional information, see Note 3, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Long-Term Obligations and Commitments</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 1% Notes mature in November 2021. Therefore, as of December 31, 2020, we classified the liability component of the 1% Notes as a current liability on our consolidated balance sheet.</div>

<div><br/></div>

<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 2020, the FASB issued guidance simplifying the accounting for convertible debt instruments. See the section titled &#8220;Impact of Recently Issued Accounting Standards&#8221; below for details.</div>

<div><br/></div>

<div style="text-align: left; 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 0.125% Notes, we entered into a call spread transaction, which was 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 Derivatives and Hedging &#8211; Contracts in Entity&#8217;s Own Equity 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 sheet. We reassess our ability to continue to classify the note hedges and warrants in shareholders&#8217; equity at each reporting period.</div>

<div><br/></div>

<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">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;">Through 2020, we had two operating segments, our Ionis Core segment and Akcea Therapeutics. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Akcea was focused on developing and commercializing medicines to treat patients with serious and rare diseases. We have provided segment financial information and results for our Ionis Core segment and our Akcea Therapeutics segment based on the segregation of revenues and expenses that our chief decision maker reviewed to assess operating performance and to make operating decisions through 2020. We allocated a portion of Ionis&#8217; development, R&amp;D support and general and administrative expenses to Akcea for work Ionis performed on behalf of Akcea and we billed Akcea for these expenses.</span></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 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 held biotechnology companies; Level 2, defined as inputs other than quoted prices in active markets that are either directly or indirectly observable, which includes our fixed income securities and commercial paper classified as available-for-sale securities; and Level 3, defined as unobservable inputs in which little or no market data exists, therefore requiring us to develop our own assumptions. We classify most of our securities as Level 2. We obtain the fair value of our Level 2 investments from our custodian bank or from a professional pricing service. We validate the fair value of our Level 2 investments by understanding the pricing model used by the custodian banks or professional pricing service provider and comparing that fair value to the fair value based on observable market prices.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following tables present the major security types we held at December 31, 2020 and 2019&#160;<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">that we regularly measure and carry at fair value</span>. At December 31, 2019, our ProQR investment was <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">subject to trading restrictions until the fourth quarter of 2020, as a result we</span> included a lack of marketability discount in valuing this investment, which is a Level 3 input. As of December 31, 2020, our ProQR investment was no longer subject to trading restrictions. As of December 31, 2020, we did not have any investments which we valued using Level 3 inputs. The following tables segregate each security type by the level within the fair value hierarchy of the valuation techniques we utilized to determine the respective securities&#8217; fair value (in thousands):</div>

<div><br/></div>

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    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">At</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">December 31, 2020</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
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    <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; 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"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></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>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">846,315</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 (4)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #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>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-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>
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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: 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;">358,497</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;">358,497</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 (4)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">136,309</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-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;">136,309</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 (4)</div></div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6,225</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6,225</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;">Investment in ProQR Therapeutics N.V. (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;">2,031</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;">2,031</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;">1,745,363</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>
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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>
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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>
  </tr>
</table>

<div><br/></div>

<table cellpadding="0" cellspacing="0" id="z42641d00b2bd400e81caba6eddf342f0" 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;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">At</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">December 31, 2019</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;">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;" valign="bottom">&#160;</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;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
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  <tr>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
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    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <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="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
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  <tr>
    <td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by U.S. government agencies (7)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">329,404</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-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;">329,404</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%;" valign="bottom"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by the U.S. Treasury (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;">363,694</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;">363,694</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by states of the U.S. and political subdivisions of the states (4)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">40,407</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-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;">40,407</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px;" valign="bottom"><div><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Investment in ProQR Therapeutics N.V. (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;">4,506</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>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4,506</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: 52%; 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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2,258,985</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">782,100</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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,472,379</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">4,506</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" id="z791574a09f2444c599172d57b45fe997" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
  <tr>
    <td style="width: 36pt; vertical-align: top; align: right; 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 on our consolidated balance sheet.</div></td>
  </tr>
</table>

<div><br/></div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="za3c5f136d4254206a5ec01a41ea4efb9" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
  <tr>
    <td style="width: 36pt; vertical-align: top; align: right; 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;">$10.0 million included in cash and cash equivalents on our consolidated balance sheet, with the difference included in short-term investments on our consolidated balance sheet.</div></td>
  </tr>
</table>

<div><br/></div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z148638abbe4544afb1bfb13a3a3df99e" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
  <tr>
    <td style="width: 36pt; vertical-align: top; align: right; 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;">$17.5 million included in cash and cash equivalents on our consolidated balance sheet, with the difference included in short-term investments on our consolidated balance sheet.</div></td>
  </tr>
</table>

<div><br/></div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="zfe5f26749b614dbcb042f4c2f2ba5a12" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
  <tr>
    <td style="width: 36pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(4)</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Included in short-term investments.</div></td>
  </tr>
</table>

<div><br/></div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z7c2aa671a6d84170836be6a95eff7f0e" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
  <tr>
    <td style="width: 36pt; vertical-align: top; align: right; 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 on our consolidated balance sheet.</div></td>
  </tr>
</table>

<div><br/></div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="zae152b0de27346b784a63d2fad55dc16" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
  <tr>
    <td style="width: 36pt; vertical-align: top; align: right; 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;">$19.0 million included in cash and cash equivalents on our consolidated balance sheet, with the difference included in short-term investments on our consolidated balance sheet.</div></td>
  </tr>
</table>

<div><br/></div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z13ffd34009fd4d8ea5be9d956bd94c78" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
  <tr>
    <td style="width: 36pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(7)</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$0.8 million included in cash and cash equivalents on our consolidated balance sheet, with the difference included in short-term investments on our consolidated balance sheet.&#160; </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;">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, no assurance can be given that the final tax outcome of these matters will not be different from that which is 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 such determination is made.</div>

<div><br/></div>

<div 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.<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> 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.</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 do not provide for a U.S. income tax liability and foreign withholding taxes on undistributed foreign earnings of our foreign subsidiaries.</div>

<div><br/></div>

<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Impact of 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 June 2016, the FASB issued guidance that changes the measurement of credit losses for most financial assets and certain other instruments. If we have credit losses, this updated guidance requires us to record allowances for these instruments under a new expected credit loss model. This model requires us to estimate the expected credit loss of an instrument over its lifetime, which represents the portion of the amortized cost basis we do not expect to collect. The new guidance requires us to remeasure our allowance in each reporting period we have credit losses. We adopted this new guidance on January 1, 2020. This guidance did not have an impact on our consolidated financial statements.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In August 2018, the FASB issued clarifying guidance on how to account for implementation costs related to cloud-servicing arrangements. The guidance states that if these fees qualify to be capitalized and amortized over the service period, they need to be expensed in the same line item as the service expense and recognized in the same balance sheet category. The update can be applied either retrospectively or prospectively to all implementation costs incurred after the date of adoption. We adopted this guidance on January 1, 2020 on a prospective basis. This guidance did not have an impact on our consolidated financial statements.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In November 2018, the FASB issued clarifying guidance of the interaction between the collaboration accounting guidance and the new revenue recognition guidance we adopted on January 1, 2018 (Topic 606). Below is the clarifying guidance and how we implemented it (in italics):</div>

<div><br/></div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="zf1701d3f1d8d4160978d38fc5e5b4c66" 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; align: right; 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;">When a participant is considered a customer in a collaborative arrangement, all of the associated accounting under Topic 606 should be applied.</div></td>
  </tr>
</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z3d884347466d4766902ab98141f40262" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
  <tr>
    <td style="width: 72pt;"/>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">&#9679;</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;">We are applying all of the associated accounting under Topic 606 when we determine a participant in a collaborative arrangement is a customer.</div></td>
  </tr>
</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="zbefb18546da74bf487f114918d77add3" 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; align: right; 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;">Adds &#8220;unit of account&#8221; concept to collaboration accounting guidance to align with Topic 606. The &#8220;unit of account&#8221; concept is used to determine if revenue is recognized or if a contra expense is recognized from consideration received under a collaboration.</div></td>
  </tr>
</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z28c82932c2e1414281433d5974927174" 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: 72pt;"/>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">&#9679;</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;">We use the &#8220;unit of account&#8221; concept when we receive consideration under a collaborative arrangement to determine when we recognize revenue or a contra expense.</div></td>
  </tr>
</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="za50af4149c204796bc74ae610430cd43" 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; align: right; 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;">The clarifying guidance precludes us from recognizing revenue under Topic 606 when we determine a transaction with a collaborative partner is not a customer and is not directly related to the sales to third parties.</div></td>
  </tr>
</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="zd9d21a16a5b3482c85eb10cf58a06d3e" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
  <tr>
    <td style="width: 72pt;"/>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">&#9679;</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;">When we conclude a collaboration partner is not a customer and is not directly related to the sales to third parties, we do not recognize revenue for the transaction.</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 adopted this new guidance on January 1, 2020. This guidance did not have any impact on our consolidated financial statements.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In August 2020, the FASB issued guidance </span>which simplifies the accounting for convertible instruments<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, amends the guidance on derivative scope exceptions for contracts in an entity&#8217;s own equity, and modifies the guidance on diluted earnings per share calculations as a result of these changes. Under our current outstanding convertible debt arrangements, we anticipate the following impacts:</span></div>

<div><br/></div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="zcbb885b9cab547a1b31cd283712248a2" 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: 36pt; vertical-align: top; align: right; 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;">We will no longer separate our existing convertible debt into liability and equity components. Therefore, we will no longer recognize a debt discount for the value of the conversion option, instead we will record the face value of the convertible debt as a liability on our consolidated balance sheet;</div></td>
  </tr>
</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z66fb90d1a5be4351bc55d49e62d382d6" 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; align: right; 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;">We will record cash interest expense plus amortization of debt issuance costs to interest expense. Since we will not recognize a debt discount, we will no longer record the amortization of a debt discount to interest expense; and</div></td>
  </tr>
</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="ze1e1f5e6552b4bfc822ec7f94c42c685" 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; align: right; 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;">We do not expect our EPS calculation to not change under this update. We plan to continue to use the if-converted method to calculate diluted earnings per share.</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 plan to adopt this guidance in the first quarter of 2021 under the full retrospective approach, meaning we will apply the guidance to all periods presented beginning in the first quarter of 2021.</div>
<span></span>
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<span style="display: none;">v3.20.4</span><table class="report" border="0" cellspacing="2" id="idm140142735707992">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Investments<br></strong></div></th>
<th class="th" colspan="1">12 Months Ended</th>
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<tr><th class="th"><div>Dec. 31, 2020</div></th></tr>
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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="top.Show.showAR( this, 'defref_us-gaap_InvestmentTextBlock', window );">Investments</a></td>
<td class="text">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2. Investments</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following table summarizes the contract maturity of the available-for-sale securities we held as of December 31, 2020:</div>

<div><br/></div>

<table cellpadding="0" cellspacing="0" id="zb8b331d548474cfd89ae511966ada4d1" 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;">One year 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;">73</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 one year but within two years</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;">18</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
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  <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 two years but within <span style="-sec-ix-hidden:Fact_5b50da2d62974df399b2ebfcfccf0c30">three and a half years</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;">9</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
  <tr>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
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</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, 2020, 91 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;">At December 31, 2020, we had an ownership interest of less than 20 percent <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">in </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">seven</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> private companies and </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">two</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> public companies with which we conduct business. The privately-held companies are </span>Aro Biotherapeutics, Atlantic Pharmaceuticals Limited, Dynacure SAS, Empirico, Inc., Flamingo Therapeutics BV, Seventh Sense Biosystems and Suzhou Ribo Life Science Co, Ltd. The publicly traded companies are ATL and ProQR.</div>

<div><br/></div>

<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>

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    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
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    <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, 2020</div></td>
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    <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; padding-bottom: 2px;" valign="bottom">&#160;</td>
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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>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>
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  <tr>
    <td style="vertical-align: bottom; width: 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 (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;">$</div></td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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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;">$</div></td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></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>
  </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;">94,234</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;">354</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(2</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;">94,586</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 (2)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">307,576</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">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;">(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;">307,800</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 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;">104,271</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;">196</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;">(12</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;">104,455</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;">5,191</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;">(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"><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;">5,184</div></td>
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  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total securities with a maturity of one year or less</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,025,454</div></td>
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  <tr>
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  <tr>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
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  </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>
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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>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #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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  </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;">31,779</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;">91</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>
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    <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>
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  </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>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
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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>
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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></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;">1,041</div></td>
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  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total securities with a maturity of 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;">488,316</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>
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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;">(69</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;">493,847</div></td>
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  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total 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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,513,770</div></td>
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    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">8,577</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">(140</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;">1,522,207</div></td>
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  </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>
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    <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>
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    <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>
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    <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>
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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">&#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; 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;" 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%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
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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>
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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>
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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>
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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"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total equity securities</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">19,774</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">15,938</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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(2,681</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">33,031</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; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total available-for-sale and equity securities</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,533,544</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">24,515</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>
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    <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;">(2,821</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;">1,555,238</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>
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<div><br/></div>

<table cellpadding="0" cellspacing="0" id="za103de634c4d4cc69d2c374dfbfb01cd" 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"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"/></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>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </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, 2019</div></td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><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>
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    <td colspan="2" style="vertical-align: bottom; border-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 (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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">669,665</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,451</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">671,073</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>
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    <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;">188,216</div></td>
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  <tr>
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  </tr>
  <tr>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
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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>
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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;">1,208,510</div></td>
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  </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;">428,627</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>
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    <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;">(43</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;">431,495</div></td>
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  </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;">140,988</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">57</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" 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%; background-color: #CCEEFF; white-space: nowrap;" valign="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;">140,928</div></td>
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  </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;">35,822</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>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; 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: #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>
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    <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;">35,819</div></td>
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  </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;">19,309</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>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">18</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>
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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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  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total securities with a maturity of more than one year</div></td>
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    <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;">624,746</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;">2,995</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;">(178</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;">627,563</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total 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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,831,362</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">5,007</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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(296</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">1,836,073</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; 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;">Total equity securities included in other current assets (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"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4,712</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(870</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">3,842</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;">Total equity securities included in deposits and other assets (4)</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;">10,000</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10,000</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total 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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">14,712</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">&#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"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(870</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">13,842</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; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total available-for-sale and equity securities</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,846,074</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">5,007</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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(1,166</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">1,849,915</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 style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">________________</div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z61f6c267d21144238581ae579b649dc5" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
  <tr>
    <td style="width: 36pt; vertical-align: top; align: right; 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;">We hold our available-for-sale securities at amortized cost.</div></td>
  </tr>
</table>

<div><br/></div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z79a8f59d9a7f407a9a6b439f8b61c468" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
  <tr>
    <td style="width: 36pt; vertical-align: top; align: right; 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;">Includes investments classified as cash equivalents on our consolidated balance sheet.</div></td>
  </tr>
</table>

<div><br/></div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z306650d01b4d4023a6e695c9eb77db2c" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
  <tr>
    <td style="width: 36pt; vertical-align: top; align: right; 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 equity securities included in other current assets consisted of our investments in publicly traded companies. We recognize publicly traded equity securities at fair value.</div></td>
  </tr>
</table>

<div><br/></div>

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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;">The </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">following is a summary of our investments we considered to be temporarily impaired at</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#160;</span>December 31, 2020<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;">(in thousands). All of these investments have less than 12 months of temporary impairment. </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We believe that the decline in value of these securities is temporary and is primarily related to the change in market interest rates since purchase. We believe it is more likely than not that we will be able to hold our debt securities to maturity. Therefore, we anticipate full recovery of our debt securities&#8217; amortized cost basis at maturity.</span></div>

<div><br/></div>

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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
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    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; 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>
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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>
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<span style="display: none;">v3.20.4</span><table class="report" border="0" cellspacing="2" id="idm140142733891080">
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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;">3. Long-Term Obligations and Commitments</div>

<div><br/></div>

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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The carrying value of our long-term obligations was as follows (in thousands):</div>

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  <tr>
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    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2020</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <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;">2019</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;">0.125 percent 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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">455,719</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">434,711</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;">1 percent convertible senior notes (1)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
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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;">275,333</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Long-term mortgage debt</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">59,984</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">59,913</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;">Leases and other obligations</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;">30,710</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;">17,569</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%; 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</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">839,574</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">787,526</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; 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;">Less: current portion (1)</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;">(300,462</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;">(2,026</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: 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; 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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">539,112</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">785,500</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" id="za3bbe36629904c01b690cbe109c76d9b" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
  <tr>
    <td style="width: 36pt; vertical-align: top; align: right; 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;">We classified the carrying value of our 1% Notes as a current liability on our consolidated balance sheet at December 31, 2020 because it matures in November 2021.</div></td>
  </tr>
</table>

<div><br/></div>

<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Convertible Notes and Call Spread</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;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">0.125 Percent</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-style: italic;">Convertible Senior Notes</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 December 2019, we entered into privately negotiated exchange and/or subscription agreements with certain new investors and certain holders of our existing <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">1%</span> Notes to exchange $375.6 million of our <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">1%</span> Notes for $439.3<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#160;</span>million of our 0.125% Notes, and to issue $109.5 million of our 0.125% Notes. We completed this exchange to reduce our cash interest payments, increase our conversion price and extend our maturity for a large portion of our debt. Additionally, i<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">n conjunction with the December 2019 exchange, 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<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> by increasing the effective conversion price even further.</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;">Interest is payable semi-annually on June 15 and December 15 of each year for the <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">0.125%</span> Notes. The <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">0.125%</span> Notes are convertible at the option of the note holders prior to August 1, 2024 only under certain conditions. On or after August 1, 2024, the <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">0.125%</span> Notes are initially convertible into approximately 6.6 million shares of common stock at a conversion price of approximately $83.28 per share. We will 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 <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">0.125%</span> Notes prior to maturity, and no sinking fund is provided for them. If we undergo a fundamental change, holders may require us to purchase for cash all or any portion of their <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">0.125%</span> Notes at a purchase price equal to 100 percent of the principal amount of the notes to be purchased, plus accrued and unpaid interest to, but excluding, the fundamental change purchase 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;">At December 31, 2020, we had the following <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">0.125%</span> Notes outstanding (amounts in millions except price per share data):</div>

<div><br/></div>

<table cellpadding="0" cellspacing="0" id="zd6b190b45e7940aebc9709e23b39ca57" 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; white-space: nowrap;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/></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;">0.125% <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Notes</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: top; width: 88%; background-color: #CCEEFF; white-space: nowrap;" 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; 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;">548.8</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; white-space: nowrap;" 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; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: top;" valign="bottom"><div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">December 15, 2024</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 88%; background-color: #CCEEFF; white-space: nowrap;" 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%; 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;">0.125</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%; white-space: nowrap;" 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%; white-space: nowrap;" valign="bottom">&#160;</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; text-align: right; width: 9%; white-space: nowrap;" 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; white-space: nowrap;" 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; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6.6</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
</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 table summarizes information about the equity and liability components of our outstanding </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">0.125%</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> Notes (in millions). We measured the fair values of the convertible notes outstanding based on quoted market prices, which is a Level 2 measurement at December 31, </span>2020<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> and </span>2019<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">:</span></div>

<div><br/></div>

<table cellpadding="0" cellspacing="0" id="z9adf776942de41cfa98e122ffee7ca9c" 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"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/></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; text-indent: 16pt;">2020</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;">2019</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;">Fair value of outstanding 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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">564.9</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">558.7</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>
  <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;">Principal amount of convertible notes outstanding</div></td>
    <td colspan="1" 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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">548.8</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">548.8</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;">Unamortized portion of debt discount</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">86.0</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">105.2</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 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 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"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">455.7</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">434.7</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: 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;">Carrying value of equity component</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">105.8</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">105.8</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
</table>

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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;">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;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Additionally, i</span>n conjunction with the December 2019 exchange, 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 style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">0.125%</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> Notes</span> by increasing the conversion price even further. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">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. 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><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">0.125%</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> Notes</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. </span>We accounted for our call spread transactions using the Derivatives and Hedging &#8211; Contracts in Entity&#8217;s Own Equity accounting guidance contained in Topic 815. We determined that the call spread transactions meet the definition of a derivative, are indexed to our stock and meet the criteria to be classified in shareholders&#8217; equity.</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;">Similar to our </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">0.125%</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> Notes</span><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><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">0.125%</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> Notes</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. The note hedges will expire upon maturity of </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">0.125%</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> Notes</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, or December 2024. The note hedges and warrants are separate transactions and are not part of the terms of our </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">0.125%</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> Notes</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. The holders of the </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">0.125%</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> Notes</span><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;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We recorded the aggregate amount paid for the note hedges and the aggregate amount received for the warrants in additional paid-in capital in our consolidated balance sheet. </span>We reassess our ability to continue to classify the note hedges and warrants in shareholders&#8217; equity at each reporting period. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We excluded shares under the note hedges from our calculation of diluted earnings per share as they were antidilutive. We will include the shares issuable under the 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.</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;">1 Percent Convertible Senior Notes</div>

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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In November 2014, we completed a $500 million offering of convertible senior notes, which mature in 2021 and bear interest at 1 percent. We used a substantial portion of the net proceeds from the issuance of the 1% Notes to repurchase $140 million in principal of our <span style="-sec-ix-hidden:Fact_5720e35e625f4851a419d661f07222c0">2&#190; percent</span> convertible senior notes, or <span style="-sec-ix-hidden:Fact_aab0fa84211849a9a9227eb0f2f81996">2&#190;%</span>% Notes. In December 2016, we issued an additional $185.5 million of 1% Notes in exchange for the redemption of $61.1 million of our <span style="-sec-ix-hidden:Fact_1a854ab02ffa46d48ab09b0a92e8e673">2&#190;%</span>% Notes. In December 2019, we exchanged a portion of our 1% Notes for <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">0.125%</span> Notes. As a result, the principal balance of 1% Notes was $309.9 million. Additionally, we recorded a $21.9 million non-cash loss on early retirement of debt, reflecting the early retirement of a significant portion of our 1% Notes in December 2019.</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, 2020, we had the following 1% Notes outstanding (amounts in millions except price per share data):</div>

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<table cellpadding="0" cellspacing="0" id="z7c00b82b222848c08f211e04a12df732" 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; white-space: nowrap;" valign="bottom"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/></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;">1% 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; white-space: nowrap;" 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; 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;">309.9</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: top; white-space: nowrap;" 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; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: top;" valign="bottom"><div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">November 30, 2021</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; background-color: #CCEEFF; white-space: nowrap;" 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; background-color: #CCEEFF; white-space: nowrap;" 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;">1 percent</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 88%; white-space: nowrap;" 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%; white-space: nowrap;" valign="bottom">&#160;</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; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">66.81</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; white-space: nowrap;" 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; 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;">4.6</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
</table>

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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Interest is payable semi-annually in arrears on May 15 and November 15 of each year for the 1% Notes. The 1% Notes are convertible at the option of the note holders prior to July 1, 2021 only under certain conditions. On or after July 1, 2021, the 1% Notes are initially convertible into approximately 4.6 million shares of common stock at a conversion price of approximately $66.81 per share. We will 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 1% Notes prior to maturity, and no sinking fund is provided for them. If we undergo a fundamental change, holders may require us to purchase for cash all or any portion of their 1% Notes at a purchase price equal to 100 percent of the principal amount of the notes to be purchased, plus accrued and unpaid interest to, but excluding, the fundamental change purchase date.</div>

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<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="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 table summarizes information about the equity and liability components of our outstanding </span>1%<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> Notes (in millions). We measured the fair values of the convertible notes outstanding based on quoted market prices, which is a Level 2 measurement at December 31, </span>2020<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> and </span>2019<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">:</span></div>

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    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/></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; text-indent: 16pt;">2020</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;">2019</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;">Fair value of outstanding 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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">338.5</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">354.8</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: 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;">Principal amount of convertible notes outstanding</div></td>
    <td colspan="1" 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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">309.9</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">309.9</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;">Unamortized portion of debt discount</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">15.8</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">32.8</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: 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;">Current/long-term 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"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">293.2</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">275.3</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: 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;">Carrying value of equity component</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">33.5</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">33.5</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>
</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 account for our convertible notes using an accounting standard that requires us to assign a value to our convertible debt equal to the estimated fair value of similar debt instruments without the conversion feature and to record the remaining portion in equity. As a result, we recorded our convertible notes at a discount, which we are amortizing as additional non-cash interest expense over the expected life of the respective debt. We determined our nonconvertible debt borrowing rate using a combination of the present value of the debt&#8217;s cash flows and a Black-Scholes valuation model. The following table summarizes the nonconvertible borrowing rate, effective interest rate and amortization period of our debt discount for our convertible notes:</div>

<div><br/></div>

<table cellpadding="0" cellspacing="0" id="z2fe2c231c3944d6a8692011908bb0bdd" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
  <tr>
    <td style="width: 39.54%; vertical-align: bottom;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"/></td>
    <td style="width: 2.25%; vertical-align: bottom;">&#160;</td>
    <td style="width: 28.82%; vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">1% Notes</div></td>
    <td style="width: 1.39%; vertical-align: top;">&#160;</td>
    <td style="width: 28%; 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;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">0.125%</span> Notes</div></td>
  </tr>
  <tr>
    <td style="width: 39.54%; vertical-align: bottom; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Nonconvertible debt borrowing rate</div></td>
    <td style="width: 2.25%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 28.82%; vertical-align: bottom; background-color: #CCEEFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">7.4 percent</div></td>
    <td style="width: 1.39%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 28%; vertical-align: bottom; background-color: #CCEEFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4.4 percent</div></td>
  </tr>
  <tr>
    <td style="width: 39.54%; vertical-align: bottom; background-color: #FFFFFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Effective interest rate (1)</div></td>
    <td style="width: 2.25%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 28.82%; vertical-align: bottom; background-color: #FFFFFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">7.5 percent</div></td>
    <td style="width: 1.39%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 28%; vertical-align: bottom; background-color: #FFFFFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4.9 percent</div></td>
  </tr>
  <tr>
    <td style="width: 39.54%; vertical-align: bottom; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Amortization period of debt discount</div></td>
    <td style="width: 2.25%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 28.82%; vertical-align: bottom; background-color: #CCEEFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">7 years</div></td>
    <td style="width: 1.39%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 28%; vertical-align: bottom; background-color: #CCEEFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">5 years</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" id="zfe3e4e94d24b42be98cc86e80ead96fa" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
  <tr>
    <td style="width: 36pt; vertical-align: top; align: right; 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;">For our 1% Notes, our effective interest rate represents our effective interest rate after our December 2019 debt exchange.</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 total interest expense for our outstanding senior convertible notes for the years ended December 31, 2020, 2019 and 2018 included $38.7 million, $39.3 million and $35.2 million, respectively, of non-cash interest expense related to the amortization of the debt discount and 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; font-weight: bold;">Line of Credit 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;">In June 2015, we entered into a five-year revolving line of credit agreement with Morgan Stanley Private Bank, National Association, or Morgan Stanley, which we amended in February 2016. Under the amended credit agreement, Morgan Stanley provided a maximum of $30 million of revolving credit for general working capital purposes. During the third quarter of 2019, we paid off our total outstanding borrowings of $12.5 million under the agreement and subsequently terminated 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; font-style: italic; font-weight: bold;">Research and Development and Manufacturing Facilities</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In July 2017, we purchased the building that houses our primary R&amp;D facility for $79.4 million and our manufacturing facility for $14.0 million. We financed the purchase of these two facilities with mortgage debt of $60.4 million in total. Our primary R&amp;D facility mortgage has 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 are only required to make interest payments. Both mortgages mature in August 2027.</div>

<div><br/></div>

<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">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 debt and other obligation maturities, including fixed and determinable interest, at December 31, 2020 are as follows (in thousands):</div>

<div><br/></div>

<table cellpadding="0" cellspacing="0" id="z4c8baa70053148028f3836d3d205e2fe" 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;">2021</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">329,189</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;">2022</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3,495</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;">2023</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4,180</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;">2024</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">553,006</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;">2025</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3,494</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;">60,933</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;">Subtotal</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">954,297</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </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</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(300,462</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;">(21,758</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%;" valign="bottom"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Less: unamortized portion of debt discount</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(101,820</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: debt issuance costs</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(8,455</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;">Plus: lease liabilities</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;">17,310</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%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total long-term debt</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">539,112</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
</table>

<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br/></div>

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

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Carlsbad Leases</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We lease a facility adjacent to our manufacturing facility that has laboratory and office space that we use to support our manufacturing facility. We lease this space under a non-cancelable operating lease. In May 2020, we exercised our option to extend our lease, extending our lease term from June 2021 to August 2026. We have one remaining option to extend the lease for an additional five-year period.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We also lease additional office spaces in Carlsbad. We lease these spaces under non-cancelable operating leases with initial terms ending in 2023 with options to extend each of the leases for one&#160;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; font-style: italic;">Boston 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;">We entered into an operating lease agreement for office space located in Boston, Massachusetts in the second quarter of 2018. The lease commencement date was in August 2018 and we took occupancy in September 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, which commenced on August 15, 2018, and a tenant improvement allowance up to $3.8 million. We provided the lessor with a letter of credit to secure its obligations under the lease in the initial amount of $2.4 million, to be reduced to $1.8 million on the third anniversary of the rent commencement date and to $1.2 million on the fifth anniversary of the rent commencement date if we meet certain conditions set forth in the lease at each such time.</div>

<div><br/></div>

<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.</div>

<div><br/></div>

<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" id="z0a8a9123d7d24adcb53d3ae530505e1b" 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"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/></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;">At December 31, 2020</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 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 (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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">13.1</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 88%;" valign="bottom"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Operating lease liabilities (2)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">17.3</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: 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;">7.2 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;">7.0</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: 10pt;">________________</div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z73aea46a179a456ab91ef0c8e323ab62" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
  <tr>
    <td style="width: 36pt; vertical-align: top; align: right; 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 <span style="-sec-ix-hidden:Fact_f81ca57385a04657b8ecd0f06d505159">deposits and other assets</span> on our consolidated balance sheet.</div></td>
  </tr>
</table>

<div><br/></div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="zd0fe2a08d108427ab40244fed97b9a07" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
  <tr>
    <td style="width: 36pt; vertical-align: top; align: right; 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;">Current portion of $2.0 million was included in <span style="-sec-ix-hidden:Fact_530181678e9244af8b37885d3ba85980">current portion of long-term obligations</span> on our consolidated balance sheet, with the difference included in <span style="-sec-ix-hidden:Fact_9c37cb3853f74a4f821bbe4ed37a06ba">long-term obligations</span>.</div></td>
  </tr>
</table>

<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">During the years ended December 31, 2020, 2019, and 2018 we paid $3.8 million, $3.9 million and $1.7 million of lease payments, which were included in operating activities in our consolidated statement 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, 2020, the future payments for our operating lease liabilities are as follows (in thousands):</div>

<div><br/></div>

<table cellpadding="0" cellspacing="0" id="z04402bd2033b49df92fb5d8cb974b10a" 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"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/></td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Operating</span> <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Leases</span></div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;" 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; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">$</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: 88%;" valign="bottom"><div style="text-align: justify; margin-left: 18.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2021</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3,193</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;">2022</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2,968</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;">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;">2,707</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;">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">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2,583</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;">2025</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2,442</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%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: justify; 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; 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;">7,038</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: 88%;" 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%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">20,931</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: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">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">&#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: 88%; padding-bottom: 2px;" valign="bottom"><div style="text-align: left; margin-left: 18.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Imputed interest</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;">(3,621</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: left; margin-left: 36.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total operating lease 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;">17,310</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;">Rent expense was $3.7 million, $3.6 million and $2.6 million for the years ended December 31, 2020, 2019 and 2018, respectively. </div>
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<span style="display: none;">v3.20.4</span><table class="report" border="0" cellspacing="2" id="idm140142826847816">
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<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Stockholders' Equity<br></strong></div></th>
<th class="th" colspan="1">12 Months Ended</th>
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<tr><th class="th"><div>Dec. 31, 2020</div></th></tr>
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<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_StockholdersEquityNoteAbstract', window );"><strong>Stockholders' Equity [Abstract]</strong></a></td>
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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;">4. Stockholders</span>&#8217;<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"> Equity</span></div>

<div><br/></div>

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

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We are authorized to issue up to 15 million shares of &#8220;blank check&#8221; Preferred Stock. As of December 31, 2020, 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, 2020.</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>

<div><br/></div>

<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, 2020 and 2019, we had 300 million shares of common stock authorized, of which 140.4 million and 140.3 million were issued and outstanding, respectively. As of December 31, 2020, total common shares reserved for future issuance were 26.1 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, 2020, 2019 and 2018, we issued 1.7 million, 3.1 million and 1.5 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 $52.0 million, $119.7 million and $27.9 million in 2020, 2019 and 2018, respectively.</div>

<div><br/></div>

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

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<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In September 2019, our board of directors approved a share repurchase program of up to $125 million of our common stock. In 2019, we repurchased 535,000 shares for $34.4 million. In the first quarter of 2020, we repurchased an additional 1.5 million shares for $90.5 million.</div>

<div><br/></div>

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

<div><br/></div>

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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">1989 Stock Option Plan</div>

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<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In June 1989, our Board of Directors adopted, and the stockholders subsequently approved, a stock option plan that, as amended, provides for the issuance of non-qualified and incentive stock options for the purchase of up to 20.0 million shares of common stock to our employees, directors, and consultants. The plan expires in January 2024. The 1989 Plan does not allow us to grant stock bonuses or restricted stock awards and prohibits us from repricing any options outstanding under the plan unless our stockholders approve the repricing. Options vest over a four-year period, with 25percent exercisable at the end of one year from the date of the grant and the balance vesting ratably, on a monthly basis, thereafter and have a term of seven years. At December 31, 2020, a total of 30 thousand options were outstanding, of which options to purchase 30 thousand shares were exercisable, and 50 thousand shares were available for future grant under the 1989 Plan.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: -18pt; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">2011 Equity Incentive Plan</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In March 2011, our Board of Directors adopted, and the stockholders subsequently approved, a stock option plan that provides for the issuance of stock options, stock appreciation rights, restricted stock awards, restricted stock unit awards, and performance cash awards to our employees, directors, and consultants. In June 2015, May 2017 and June 2019, after receiving approval from our stockholders, we amended our 2011 Equity Incentive Plan 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. 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 options and restricted stock unit awards to our employees, directors and consultants. 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, 2020, a total of 11.4 million options were outstanding, of which 6.7 million were exercisable, 2.2 million restricted stock unit awards were outstanding, and 4.3 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. The stock options and restricted stock unit awards we issued to Dr. Stanley T. Crooke in his former role as chief executive officer and certain stock options and restricted stock unit awards we issued to B. Lynne Parshall in her former role as chief operating officer will accelerate upon a change of control, as defined in the 2011 Plan. 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. If we terminate one of our executive officers or if an executive officer 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 executive officers&#8217; 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 Acquisition in October 2020, we assumed the unallocated portion of the available share reserve under the Akcea 2015 Equity Incentive Plan. In December 2020, we amended and restated the Akcea 2015 equity plan, including renaming the plan as the Ionis Pharmaceuticals, Inc. 2020 Equity Incentive Plan, or 2020 Plan. The 2020 Plan provided for the issuance of up to </span>2.6<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million shares of our Common Stock to our employees, directors and consultants who were employees of Akcea prior to the Akcea Acquisition.</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 options and restricted stock unit awards to our eligible employees, directors and consultants. We have granted stock options to our employees under the 2020 Plan which vest annually over a four-year period. At December 31, 2020, a total of 0.01 million options were outstanding, of which none were exercisable, and 2.6 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" id="z1d2b880620554f7a8d859c8ac182b8a5" 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; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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>
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<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z5ac0a33cd456453795b7a6dee28dcaac" 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; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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>
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<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z0d47e7cb347a4be8aaf4f46a432dbcc2" 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; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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>
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<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z52630d9833314cd2b584bf1e2514e71e" 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; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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>
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<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z38a0cb52edc340b7a2694317e322760e" 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; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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>
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<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z4573ab04cbdd482b87e9a572545982dc" 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; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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>
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<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> </span><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: -18pt; margin-left: 54pt; 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 September 2001, our Board of Directors adopted, and the stockholders subsequently approved, an amendment and restatement of the 1992 Non-Employee Directors&#8217; Stock Option Plan, which provides for the issuance of non-qualified stock options and restricted stock units to our non-employee directors. The name of the resulting plan is the 2002 Non-Employee Directors&#8217; Stock Option Plan, or the 2002 Plan. In June 2015, after receiving approval from our stockholders, we amended our 2002 Plan to increase the total number of shares reserved for issuance from 1.2 million to 2.0 million. In June 2020, after receiving approval from our stockholders, we further amended our 2002 Plan. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">The amendments included:</span></div>

<div><br/></div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z5e4f865f85114d45a89e7bb61564e0e0" 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; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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 </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">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" id="z920b1672958340049e91b73e544ffb88" 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; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">A reduction to the amount of the automatic awards under the plan;</div></td>
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<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z9dc5c7c10f39451a90ae42ff5d29e107" 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; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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" id="z2ecc905910434dea959a202548f8b597" 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; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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, 2020, a total of 1.0 million options were outstanding, of which 0.6 million were exercisable, 0.1 million restricted stock unit awards were outstanding, and 0.8 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 June 2009, our Board of Directors adopted, and the stockholders subsequently approved, the amendment and restatement of the ESPP and we reserved an additional 150,000 shares of common stock for issuance thereunder. In each of the subsequent years until 2019, we reserved an additional 150,000 shares of common stock for the ESPP resulting in a total of 3.2 million shares authorized under the plan as of December 31, 2020. The ESPP permits full-time employees to purchase common stock through payroll deductions (which cannot exceed 10percent of each employee&#8217;s compensation) at the lower of 85percent of fair market value at the beginning of the purchase period or the end of each purchase period. Under the amended and restated ESPP, employees must hold the stock they purchase for a minimum of six months from the date of purchase. During 2020, employees purchased and we issued to employees 0.06 million shares under the ESPP at a weighted average price of $43.65 per share. At December 31, 2020, there were 0.7 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, 2020 (in thousands, except per share and contractual life data):</div>

<div><br/></div>

<table cellpadding="0" cellspacing="0" id="zefbaea486274447a80de6c1c839baaef" 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; background-color: #CCEEFF;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
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  <tr>
    <td style="vertical-align: bottom;" valign="bottom"><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>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">59.89</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>
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  <tr>
    <td style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"><div style="text-align: justify; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Exercised</div></td>
    <td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>
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    <td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">40.88</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>
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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;">(361</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;">56.48</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;">Outstanding at December 31, 2020</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;">12,335</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;">54.14</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;">4.16</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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">55,885</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; padding-bottom: 4px;" valign="bottom"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Exercisable at December 31, 2020</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">7,366</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">52.45</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;">3.16</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;">43,267</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 $29.43, $28.76 and $25.49 for the years ended December 31, 2020, 2019 and 2018, respectively. The total intrinsic value of options exercised during the years ended December 31, 2020, 2019 and 2018 were $15.5 million, $83.8 million and $34.8 million, respectively, which we determined as of the date of exercise. The amount of cash received from the exercise of stock options was $43.7 million, $105.9 million and $18.9 million for the years ended December 31, 2020, 2019 and 2018, respectively. For the year ended December 31, 2020, the weighted-average fair value of options exercised was $55.33. As of December 31, 2020, total unrecognized compensation cost related to non-vested stock options was $54.1 million. We expect to recognize this cost over a weighted average period of 1.1 years. We will adjust the total unrecognized compensation cost for future changes in estimated forfeitures.</div>

<div><br/></div>

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

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following table summarizes the RSU activity for the year ended December 31, 2020 (in thousands, except per share data):</div>

<div><br/></div>

<table cellpadding="0" cellspacing="0" id="zda6995a5dbd94d9990cbafed46af3aa1" 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"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/></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;">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;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
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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;">1,866</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #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"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">55.80</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>
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    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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  </tr>
  <tr>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">53.68</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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    <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;">(134</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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">58.96</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 76%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Non-vested at December 31, 2020</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">58.81</div></td>
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  </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, 2020, 2019 and 2018, the weighted-average grant date fair value of RSUs granted was $60.86, $60.23 and $51.06 per RSU, respectively. As of December 31, 2020, total unrecognized compensation cost related to RSUs was $55.3 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: 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, 2020, 2019 and 2018 (in thousands):</div>

<div><br/></div>

<table cellpadding="0" cellspacing="0" id="zf582273af94a47d4a55e546cbe3c3f20" 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"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/></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;">2020</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;">2019</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;">2018</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 products sold</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,991</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">438</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">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>
  </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;">115,584</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;">95,348</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;">76,557</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;">112,542</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; 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;">50,788</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;">54,595</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;">230,117</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">146,574</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">131,312</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;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Our non-cash stock-based compensation expense included </span>$94.8 million, $37.1 million and $44.3 million <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">of stock-based compensation expense for Akcea employees for the years ended December 31, 2020, 2019 and 2018, respectively.</span></div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In October 2020, as part of the Akcea Acquisition, Akcea&#8217;s outstanding equity awards vested under Akcea&#8217;s Plan. As a result, in the fourth quarter of 2020, we recognized all unrecognized stock-based compensation ($59.3 million) under Akcea&#8217;s Plan. See Note 7, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Akcea Acquisition</span>, in the Notes to the Consolidated Financial Statements for further details.</div>

<div><br/></div>

<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 the third quarter of 2019, </span>three<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> Akcea executive officers terminated their employment and entered into separation agreements with Akcea. As a result, in the third quarter of 2019, Akcea reversed $</span>19.1<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million of stock-based compensation expense it had previously recognized related to the executive officers&#8217; stock options and RSUs that were no longer going to vest.</span></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;">Determining Fair Value</div>

<div><br/></div>

<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;">Valuation.</span> We measure stock-based compensation expense for equity-classified awards, principally related to stock options, RSUs, and stock purchase rights under the ESPP at the grant date, based on the estimated fair value of the award and we recognize the expense over the employee&#8217;s requisite service period. We value RSUs based on the market price of our common stock on the date of grant.</div>

<div><br/></div>

<div 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. The expected term of stock options granted represents the period of time that we expect them to be outstanding. We estimate the expected term of options granted based on actual and projected exercise patterns. We recognize compensation expense for stock options granted, RSUs, 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;">For the years ended December 31, 2020, 2019 and 2018, we used the following weighted-average assumptions in our Black-Scholes calculations:</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Ionis Employee Stock Options:</div>

<div><br/></div>

<table cellpadding="0" cellspacing="0" id="z5de1b8387f794ea89da0aaf36c178756" 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"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/></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;">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;">2020</div></td>
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    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" 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;">Risk-free interest rate</div></td>
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  </tr>
  <tr>
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  <tr>
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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; font-style: italic;">Ionis Board of Director Stock Options:</div>

<div><br/></div>

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    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
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  <tr>
    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
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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;">Risk-free interest rate</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
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  </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>
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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;">0.0</div></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"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.0</div></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;">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 colspan="1" style="text-align: left; vertical-align: bottom; 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>
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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>
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  </tr>
  <tr>
    <td style="vertical-align: bottom;" valign="bottom"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Expected life</div></td>
    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom;" valign="bottom"><div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6.6 years</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>
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</table>

<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Ionis ESPP:</div>

<div><br/></div>

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  <tr>
    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/></td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </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="text-align: 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;">2019</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;">2018</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;">0.8</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <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>
    <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"><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>
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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;">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;">47.9</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">45.6</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">47.3</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: bottom;" valign="bottom"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Expected life</div></td>
    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom;" valign="bottom"><div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6 months</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom;" valign="bottom"><div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6 months</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom;" valign="bottom"><div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6 months</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
</table>

<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Risk-Free Interest Rate.</span> We base the risk-free interest rate assumption on observed interest rates appropriate for the term of our stock option plans or ESPP.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Dividend Yield.</span> We base the dividend yield assumption on our history and expectation of dividend payouts. We have not paid dividends in the past and do not expect to in the future.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Volatility.</span> We use an average of the historical stock price volatility of our stock for the Black-Scholes model. We computed the historical stock volatility based on the expected term of the awards.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Expected Life. </span>The expected term of stock options we have granted represents the period of time that we expect them to be outstanding. We estimated the expected term of options we have granted based on actual and projected exercise patterns.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Forfeitures.</span> We reduce stock-based compensation expense for estimated forfeitures. We estimate forfeitures at the time of grant and revise, if necessary, in subsequent periods if actual forfeitures differ from those estimates. We estimate forfeitures based on historical experience.</div>

<div><br/></div>

<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 stock plans, Akcea had its own stock plan prior to the Akcea Acquisition, referred to as the Akcea 2015 Equity Incentive Plan, or Akcea Plan. Under the Akcea Plan, Akcea granted options and RSUs.</div>

<div><br/></div>

<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, 2020, 2019 and 2018, we used the following weighted-average assumptions in our Black-Scholes calculations for the Akcea 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; font-style: italic;">Akcea Employee Stock Options:</div>

<div><br/></div>

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    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/></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;">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;">2020</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;">2019</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;">2018</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Risk-free interest rate</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1.1</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;">2.2</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;">2.8</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 64%;" valign="bottom"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Dividend yield</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.0</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.0</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.0</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Volatility</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">75.0</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;">75.4</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">77.1</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;" 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;">6.08 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;">6.09 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;">6.08 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;">Akcea Board of Director Stock Options:</div>

<div><br/></div>

<table cellpadding="0" cellspacing="0" id="z65411e08eef04f55b90f91e957d37dce" 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"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/></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;">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;">2020</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;">2019</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;">2018</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Risk-free interest rate</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Akcea ESPP:</div>

<div><br/></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 colspan="2" style="vertical-align: bottom;" valign="bottom"><div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6 months</div></td>
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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>

<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 summarizes the Black-Scholes input methodology for Akcea options that differs from the methodology we use for Ionis 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;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Volatility.</span> Since Akcea did not have sufficient history to estimate the volatility of its common stock, Akcea calculated its expected volatility based on a blend of its historical volatility and reported data from selected publicly traded peer companies for which historical information was available.</div>

<div><br/></div>

<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>Since Akcea did not have sufficient historical information, it used the simplified method for estimating its expected term. Under the simplified method Akcea calculated its expected term as the average time-to-vesting and the contractual life of the 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; font-style: italic;">Akcea 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 was based on the market price of Akcea&#8217;s common stock on the date of grant. Akcea granted RSUs with various vesting terms between six months and four years. The weighted-average grant date fair value of RSUs granted to employees for years ended December 31, 2020 and 2019 was $15.57 and $21.95 per share, respectively.</div>
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<span style="display: none;">v3.20.4</span><table class="report" border="0" cellspacing="2" id="idm140142736039720">
<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, 2020</div></th></tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="top.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;">5. 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;">Income (loss) before income taxes is comprised of (in thousands):</div>

<div><br/></div>

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    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/></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>
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  <tr>
    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2020</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <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;">2019</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;">2018</div></td>
    <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"><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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(172,702</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">344,280</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(69,576</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;">2,670</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <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;">2,489</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;">(6,580</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>
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    <td style="vertical-align: bottom; width: 64%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Income (loss) before income taxes</div></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;">(170,032</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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">346,769</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">(76,156</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>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our income tax expense (benefit) was as follows (in thousands):</div>

<div><br/></div>

<table cellpadding="0" cellspacing="0" id="zfa527624d6724c5ba0ce2f4dc24bcb29" 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"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/></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;">2020</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;">2019</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;">2018</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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(837</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-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;">438</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;">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;">3,782</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">14,329</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(1,442</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;">518</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; 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;">413</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;">374</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>
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  <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;">3,463</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;">50,603</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
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  <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>
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  <tr>
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    <td colspan="1" style="text-align: 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>
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  <tr>
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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="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(290,511</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>
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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;">&#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>
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  </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>
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    <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;">313,271</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;">(7,096</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;">(290,511</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 64%; 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;">316,734</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>
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    <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;">43,507</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>
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    <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;">(291,141</div></td>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our expense (benefit) for income taxes differs from the amount computed by applying the U.S. federal statutory rate to income (loss) before taxes. The sources and tax effects of the differences are as follows (in thousands):</div>

<div><br/></div>

<table cellpadding="0" cellspacing="0" id="zcb2d6ab6c48e4c278e66d61bd2c81d98" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
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    <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>
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  <tr>
    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: 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;">2019</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;">2018</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
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  <tr>
    <td style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Pre-tax income (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;">$</div></td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="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;">(76,156</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>
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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;">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;">72,822</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
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  <tr>
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  <tr>
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  <tr>
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  <tr>
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  <tr>
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  <tr>
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  </tr>
  <tr>
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  </tr>
  <tr>
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  <tr>
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  <tr>
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  </tr>
  <tr>
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  <tr>
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  <tr>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>
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  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 28%; 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;">Effective rate</div></td>
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</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, 2020 and 2019 are as follows (in thousands):</div>

<div><br/></div>

<table cellpadding="0" cellspacing="0" id="zae724c9b7f994507b05f251f1d96b8e5" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
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  <tr>
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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>
  <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>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>
  </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;">83,681</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #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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  <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"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">245,746</div></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"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">210,455</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;">124,452</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #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>
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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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  <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>
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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;">98,443</div></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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  <tr>
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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>
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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;">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;">645,779</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #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"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">514,483</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
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  <tr>
    <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>
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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;">Deferred Tax Liabilities:</div></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">&#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;">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"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(2,920</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">(6,110</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;">Fixed 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;">(3,611</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;">(1,958</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </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>
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    <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>
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    <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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">633,440</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">502,531</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;">(633,440</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;">(196,974</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;">305,557</div></td>
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  </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 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;">Ionis and Akcea have filed separate U.S. federal income tax returns since Akcea&#8217;s IPO in 2017. Accordingly, we were required to assess our Ionis stand-alone and Akcea&#8217;s valuation allowances separately even though we consolidate Akcea&#8217;s financial results in our consolidated financial statements. However, as a result of the Akcea acquisition, Ionis and Akcea will file a consolidated U.S. federal income tax return beginning in the fourth quarter of 2020, and we therefore assessed our U.S. federal valuation allowance requirements on a consolidated basis as of that period. We continue to assess the state portion of our valuation allowance on a consolidated basis.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We assessed our valuation allowance requirements and recorded a valuation allowance of $313 million against all of Ionis&#8217; U.S. federal net deferred tax assets in the fourth quarter of 2020, due to uncertainties related to our ability to realize the tax benefits associated with these assets. This determination is based largely on Akcea rejoining the Ionis U.S. consolidated federal tax group in the fourth quarter of 2020. Due to Akcea&#8217;s historical and projected financial statement losses, and the negative impact this is expected to have on Ionis&#8217; consolidated taxable income, there is uncertainty of generating sufficient consolidated pre-tax income in future periods to realize the Ionis deferred tax benefits. It is also expected that Ionis&#8217; pre-tax income in future periods may be lower due to increased research and development expenses associated with our pipeline of wholly owned medicines. We now maintain a valuation allowance against all our consolidated U.S. federal and state net 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 $436 million from December 31, 2019 to December 31, 2020. $313 million of the increase related to the valuation allowance established against our beginning of the year balance of Ionis&#8217; U.S. federal net deferred tax assets as discussed above, which resulted in us recognizing income tax expense during 2020. The remaining increase in our valuation allowance related to current year changes in our net 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;">At December 31, 2020, we had federal and state, primarily California, tax net operating loss carryforwards of $243.3 million and $346.3 million, respectively. Our federal tax loss carryforwards are available indefinitely. Our California tax loss carryforwards will begin to expire in 2031. At December 31, 2020, we also had federal and California research and development tax credit carryforwards of $210.5 million and $87.4 million, respectively. Our Federal research and development tax credit carryforwards will begin to expire in 2034. Our California research and development tax credit carryforwards are available indefinitely.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Utilization of the net operating loss and tax credit carryforwards may be subject to an annual limitation due to the ownership change limitations provided by the Internal Revenue Code of 1986, as amended, and similar state provisions. The annual limitation may result in the expiration of net operating losses and credits before utilization.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We analyze filing positions in all U.S. federal, state and foreign jurisdictions where we file income tax returns, and all open tax years in these jurisdictions to determine if we have any uncertain tax positions on any of our income tax returns. We recognize the impact of an uncertain tax position on an income tax return at the largest amount that the relevant taxing authority is more-likely-than not to sustain upon audit. We do not recognize uncertain income tax positions if they have less than 50 percent likelihood of the applicable tax authority sustaining our position.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following table summarizes our gross unrecognized tax benefits (in thousands):</div>

<div><br/></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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    <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%; 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="vertical-align: bottom; width: 1%; background-color: #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%; 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>
    <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="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;">$</div></td>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Included in the balance of unrecognized tax benefits at December 31, 2020 and 2019 was $6.4 million and $0.4 million respectively, that if we recognized, could impact our effective tax rate, subject to our remaining valuation allowance. None of our unrecognized tax benefits recorded at December 31, 2018 would impact our effective tax rate, if we recognized them.</div>

<div><br/></div>

<div 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 foresee any material changes to our gross unrecognized tax benefits within the next twelve months.</div>

<div><br/></div>

<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 interest and/or penalties related to income tax matters in income tax expense. During the year ended December 31, </span>2020<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, we recognized $</span>0.3<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million of accrued interest and penalties related to gross unrecognized tax benefits</span>. We did not record any accrued interest and penalties for the years ended December 31, 2019 and 2018.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We are subject to taxation in the U.S. and various state and foreign jurisdictions. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Our tax years for 1999 through 2019 are subject to examination by the U.S. federal, state and foreign tax authorities.</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 do not provide for a U.S. income tax liability and foreign withholding taxes on undistributed foreign earnings of our foreign subsidiaries as we consider those earnings to be permanently reinvested. It is not practicable for us to calculate the amount of unrecognized deferred tax liabilities associated with these earnings.</div>
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<span style="display: none;">v3.20.4</span><table class="report" border="0" cellspacing="2" id="idm140142741571944">
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<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, 2020</div></th></tr>
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<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_CollaborativeArrangementsAndLicensingAgreementsAbstract', window );"><strong>Collaborative Arrangements and Licensing Agreements [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="top.Show.showAR( this, 'defref_us-gaap_CollaborativeArrangementDisclosureTextBlock', window );">Collaborative Arrangements and Licensing Agreements</a></td>
<td class="text">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">6. Collaborative Arrangements and Licensing Agreements</div>

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

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

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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We have several strategic collaborations with Biogen focused on using antisense technology to advance the treatment of neurological disorders. These collaborations combine our expertise in creating antisense medicines with Biogen&#8217;s expertise in developing therapies for neurological disorders. We developed and licensed to Biogen SPINRAZA, our approved medicine to treat people with spinal muscular atrophy, or SMA. We and Biogen are currently developing eight investigational medicines to treat neurodegenerative diseases under these collaborations, including medicines in development to treat people with ALS, Alzheimer&#8217;s disease<sub>&#160;</sub>and Parkinson&#8217;s disease. In addition to these medicines, our collaborations with Biogen include a substantial research pipeline that addresses a broad range of neurological diseases. From inception through December 2020, we have received more than $2.8 billion from our Biogen collaborations.</div>

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

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

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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In January 2012, we entered into a collaboration agreement with Biogen to develop and commercialize SPINRAZA, an RNA-targeted therapy for the treatment of SMA. </span>SPINRAZA is approved in over 50 countries around the world. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">From inception through December 2020, we earned more than $</span>1.3<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> billion in total revenue under our SPINRAZA collaboration, including more than $</span>930<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million in revenue from SPINRAZA royalties and more than $</span>435<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>

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

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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In December 2017, we entered into a collaboration agreement with Biogen to </span>identify <span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">new antisense medicines for the treatment of SMA</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. </span><span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Biogen has the option to license therapies arising out of this collaboration following the completion of preclinical studies. Upon licensing, Biogen </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">will be responsible for global development, regulatory and commercialization activities and costs for such therapies</span><span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. Under the collaboration agreement, we received a </span>$25 million<span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> upfront payment in the fourth quarter of 2017. We will receive development and regulatory milestone payments from Biogen if new medicines advance towards marketing approval. </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In total over the term of our collaboration, we are eligible to receive up to $</span>1.2<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> billion in license fees, milestone payments and other payments, including up to $</span>80<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million for the achievement of development milestones, up to $</span>180<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million for the achievement of commercialization milestones and up to $</span>800<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million for the achievement of sales milestones. In addition, we are eligible to receive tiered royalties </span><span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">from the mid-teens to </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">mid-</span>20 percent<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> range </span><span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">on net sales.</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> We will achieve the next payment of up to $</span>60<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">for the license of a medicine 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 one performance obligation, which was to perform R&amp;D services for Biogen. We determined the transaction price to be the $25 million upfront payment we received when we entered into the collaboration. We allocated the transaction price to our single performance obligation. In the fourth quarter of 2019, we completed our R&amp;D services performance obligation under this collaboration. We recognized revenue as we performed services based on our effort to satisfy our performance obligation relative to the total effort expected to satisfy our performance obligation. We completed our performance obligation earlier than we previously estimated, as a result, we recognized $8.3 million of additional revenue in the fourth quarter of 2019. We do not have any remaining performance obligations under this collaboration. We will receive development and regulatory milestone payments from Biogen if Biogen advances the development candidate under this collaboration toward marketing approval.</div>

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

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

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

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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In the second quarter of 2018, 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. <span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We are eligible to receive up to $</span>270<span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million in milestone payments for each medicine that achieves marketing approval. </span>In addition, we are eligible to receive tiered royalties <span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">up to the </span>20 percent range <span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">on net sales.</span>&#160;<span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">W</span>e are advancing eight programs under this collaboration and from inception through December 2020, we have received $1.05 billion in payments under this collaboration. We will achieve the next payment of $7.5 million if we advance a program<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">under this collaboration. </span></div>

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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">At the commencement of this collaboration, </span>we 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>

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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 2020, we have included $608 million <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">in payments in the transaction price for our R&amp;D services performance obligation under this collaboration, including $</span>11<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million of milestone payments we achieved in 2020 and $</span>30<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million of milestone payments we achieved in 2019. These milestone payments did not create new performance obligations because they are part of our original R&amp;D services performance obligation. Therefore, we included these amounts in our transaction price for our R&amp;D services performance obligation in the period we achieved the milestone payment. We are recognizing revenue for our R&amp;D services performance obligation as we perform services based on our effort to satisfy our performance obligation relative to our total effort expected to satisfy our performance obligation. We currently estimate we will satisfy our performance obligation at the end of the contractual term in June 2028.</span></div>

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

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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In September 2013, we and Biogen entered into a long-term strategic relationship focused on applying antisense technology to advance the treatment of neurodegenerative diseases. As part of the collaboration, Biogen gained exclusive rights to the use of our antisense technology to develop therapies for neurological diseases and has the option to license medicines resulting from this collaboration. We will usually be responsible for drug discovery and early development of antisense medicines and Biogen will have the option to license antisense medicines after Phase 2 proof-of-concept. In October 2016, we expanded our collaboration to include additional research activities we will perform. If Biogen exercises its option to license a medicine, it will assume global development, regulatory and commercialization responsibilities and costs for that medicine. We are currently advancing six investigational medicines in development under this collaboration, including <span style="-sec-ix-hidden:Fact_864d03b225ca4f548971b12e6b3ad3d0">a</span> medicine for Parkinson&#8217;s disease (ION859), three medicines for ALS (tofersen, IONIS-C9<sub>Rx</sub> and ION541), <span style="-sec-ix-hidden:Fact_7b05dc571fcb46f8bbbe0db51a44d460">a</span> medicine for multiple system atrophy (ION464) and <span style="-sec-ix-hidden:Fact_33617a5e2de04e8688f1a06dd038ea29">a</span> medicine for an undisclosed target. In the fourth quarter of 2018, Biogen exercised its option to license our most advanced ALS medicine, tofersen, our medicine in Phase 3 development for SOD1 ALS. As a result, Biogen is now responsible for global development, regulatory and commercialization activities and costs for tofersen.</div>

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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Under the terms of the agreement, we received an upfront payment of $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. For each antisense molecule that is chosen for drug discovery and development under this collaboration, we are eligible to receive up to approximately $260 million in a license fee and milestone payments per program. The $260 million per program consists of approximately $60 million in development milestones, including amounts related to the cost of clinical trials, and up to $130 million in milestone payments if Biogen achieves pre-specified regulatory milestones. In addition, we are eligible to receive tiered royalties up to the mid-teens on net sales from any antisense medicines developed under this collaboration. From inception through December 2020, we have received over $270 million in upfront fees, milestone payments and other payments under this collaboration. We will achieve the next payment of up to $10 million if we advance a program 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 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>In the third quarter of 2019, we updated our estimate of the total effort we expect to expend to satisfy our performance obligation. As a result, we recorded a cumulative catch up adjustment of $16.5 million to decrease revenue in the third quarter of 2019. During 2020, we completed our remaining<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> research and development services and recognized the remaining revenue related to this performance obligation. </span>From inception through the completion of our R&amp;D services performance obligation in <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">2020</span>, we included $145 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;">Under this collaboration, we have also generated additional payments that we concluded were not part of our R&amp;D services performance obligation. We recognized each of these payments in full in the respective quarter we generated the payment because we did not have any performance obligations for the respective payment. The following are the payments we earned:</div>

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<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="zbadc2a2f9de14e398c3088ef55129f4b" 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: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In the third quarter of 2018, we earned a $10 million milestone payment when Biogen initiated a Phase 1 study of IONIS-C9<sub>Rx</sub>.</div></td>
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<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z751ae1a2bbe04434886f78c55da5aed0" 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: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In the fourth quarter of 2018, we earned a $35 million license fee when Biogen licensed tofersen from us because Biogen had full use of the licenses without any continuing involvement from us.</div></td>
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<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z6fa2ded94c1b402e8e872dfa013d9c20" 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: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In the fourth quarter of 2018, we earned <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">a $</span>5<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million milestone when Biogen initiated a Proof-of-Concept study for tofersen.</span></div></td>
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<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z526a9a64e4fa45878f78f5f29010b15c" 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: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In the third quarter of 2019, we earned an $8 million milestone payment when Biogen initiated a Phase 1/2 study of ION859 <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">for the treatment of people with Parkinson&#8217;s disease </span>under this collaboration.</div></td>
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<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z1262dc6bc2e54fb5add1931dc4ea3baa" 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; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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 fourth quarter of 2019, we earned a $10 million milestone payment when Biogen advanced IONIS-C9<sub>Rx</sub>.</div></td>
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<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="zc5ea93483ad7438e826e674c52576e94" 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: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In the third quarter of 2020, we earned $18 million in milestone payments when Biogen initiated<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> a Phase 1/2 trial for ION464, an investigational medicine in development targeting alpha-synuclein to treat patients with multiple system atrophy.</span></div></td>
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<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z7a3bf6caaf324953b8dacbd004c6abc7" 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: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In the third quarter of 2020, w<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">e earned a $</span>10<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million milestone payment when Biogen initiated a Phase 1/2 trial for ION541, an investigational medicine in development targeting ataxin 2 to treat patients with ALS.</span></div></td>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">2012 Neurology</div>

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<div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In December 2012, we and Biogen entered into a collaboration agreement to develop and commercialize novel antisense medicines to treat neurodegenerative diseases. We are responsible for the development of each of the medicines through the completion of the initial Phase 2 clinical study for such medicine. Biogen has the option to license a medicine from each of the programs through the completion of the first Phase 2 study for each program. Under this collaboration, we are currently advancing IONIS-MAPT<sub>Rx</sub> for Alzheimer&#8217;s disease and ION582 for Angelman syndrome. If Biogen exercises its option to license a medicine, it will assume global development, regulatory and commercialization responsibilities and costs for that medicine. In the fourth quarter of 2019, Biogen exercised its option to license IONIS-MAPT<sub>Rx</sub>. We are responsible for completing the Phase 1/2 in study patients with mild AD and a one-year long-term extension study. Biogen will have responsibility 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. Over the term of the collaboration, we are eligible to receive up to $</span>210<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million in a license fee and milestone payments per program, plus a mark-up on the cost estimate of the Phase 1 and 2 studies. The $</span>210<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million per program consists of up to $</span>10<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million in development milestone payments, plus a mark-up on the cost estimate of the Phase 1 and 2 studies and up to $</span>130<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million in milestone payments if Biogen achieves pre-specified regulatory milestones. 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>three<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> programs. From inception through December 2020, we have received $</span>154<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million in payments under this collaboration, including $</span>19.5<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million we received from Biogen for achieving milestones for advancing IONIS-MAPT</span><sub>Rx </sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">during 2020. We will achieve the next payment of $</span>25<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#160;</span>million if we continue to advance 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;">Under our collaboration, we determined we had a performance obligation to perform R&amp;D services. We allocated $40 million in total payments to the transaction price for our R&amp;D services performance obligation. In the third quarter of 2019, we completed our R&amp;D services performance obligation when we designated a development candidate and Biogen accepted the development candidate. Biogen&#8217;s decision to accept the development candidate was not within our control. We were recognizing revenue as we performed services based on our effort to satisfy our performance obligation relative to the total effort expected to satisfy our performance obligation. Because Biogen accepted the development candidate earlier than when we were previously estimating, we recognized $6.3 million of accelerated revenue in the third quarter 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;">When we commenced development for IONIS-MAPT<sub>Rx</sub> we identified our development work as a separate performance obligation. We are recognizing our IONIS-MAPT<sub>Rx</sub> development performance obligation based on the percentage of completion. From inception through December 2020, we have included $57 million in the transaction price for our IONIS-MAPT<sub>Rx</sub> development performance obligation. We currently estimate we will satisfy our performance obligation in 2022. Our total transaction price for our IONIS-MAPT<sub>Rx </sub>development performance obligation includes the following payments we achieved in 2019 and 2020 related to our development work:</div>

<div><br/></div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z71d69a9d13b14163a88f7ddf594f4ca2" 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; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In the second quarter of 2019, we achieved a $7.5 million milestone payment from Biogen when we advanced IONIS-MAPT<sub>Rx</sub>.</div></td>
  </tr>
</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z2fb7af2b8d8f4262bf2f6c66a12e661a" 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; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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 fourth quarter of 2019, we achieved a $12 million milestone payment from Biogen when we entered into an agreement to conduct a long-term extension study for IONIS-MAPT<sub>Rx</sub>.</div></td>
  </tr>
</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="zebd2ef566e6449fdbc9e8c4970dcbff2" 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; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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 first quarter of 2020, we achieved a $7.5 million milestone payment from Biogen when we advanced IONIS-MAPT<sub>Rx</sub>.</div></td>
  </tr>
</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="zb1d29696a2084872b89e3dda5486ea7e" 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; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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 third quarter of 2020, we achieved a $12 million milestone payment from Biogen when we advanced IONIS-MAPT<sub>Rx</sub> in the long-term extension study for IONIS-MAPT<sub>Rx</sub>.</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;">In the fourth quarter of 2019, we identified another performance obligation upon Biogen&#8217;s license of IONIS-MAPT<sub>Rx</sub> because the license we granted to Biogen is distinct from our other performance obligations. We recognized the $45 million license fee for IONIS-MAPT<sub>Rx</sub> as revenue at that time because Biogen had full use of the license without any continuing involvement from us. Additionally, we did not have any further performance obligations related to the license after we delivered it to Biogen.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In the fourth quarter of 2019, we <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">earned a $</span>10<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million milestone payment when Biogen advanced ION582. We recognized this milestone payment in full in the fourth quarter of 2019 because we did not have any performance obligations related to this milestone payment.</span></div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">During the years ended December 31, 2020, 2019 and 2018, we earned the following revenue from our relationship with Biogen (in millions, except percentage amounts):</div>

<div><br/></div>

<table cellpadding="0" cellspacing="0" id="zd7d425e573df43b78d3759c789ce4860" 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"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/></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;">2020</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;">2019</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;">2018</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -27pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">SPINRAZA royalties (commercial revenue)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">286.6</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">293.0</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">237.9</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 64%; padding-bottom: 2px;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">R&amp;D revenue</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">122.0</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <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;">180.6</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;">137.1</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total revenue from our relationship with Biogen</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">408.6</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">473.6</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">375.0</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 64%;" valign="bottom"><div style="text-align: left; 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;">56</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">42</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;">63</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 sheet at <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">December 31, </span>2020<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> and </span>2019<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> included deferred revenue of $</span>465.8<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million and $</span>525.8<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: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Research, Development and Commercialization Partners</div>

<div><br/></div>

<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;">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 have two collaborations with AstraZeneca, one focused on the treatment of cardiovascular, renal and metabolic diseases and a <span style="-sec-ix-hidden:Fact_bba64ca284c648c3b9f851d0da94ba68">second</span> focused on the treatment of oncology diseases. We and AstraZeneca are currently developing several investigational medicines under these collaborations, including medicines in development to treat people with cardiovascular disease, a genetically associated form of kidney disease, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">nonalcoholic steatohepatitis, or NASH, and cancer</span>. From inception through December 2020, we have received more than $380 million from our AstraZeneca collaborations.</div>

<div><br/></div>

<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;">&#160;Cardiovascular, Renal and Metabolic Diseases 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 July 2015, we and AstraZeneca formed a collaboration to discover and develop antisense therapies for treating cardiovascular, renal and metabolic diseases. Under our collaboration, AstraZeneca has licensed four medicines from us:</div>

<div><br/></div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="za7c7349b939246b39fa9e2aa19d77e94" 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; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">ION449 (formerly IONIS-AZ4-2.5-L<sub>Rx</sub>), an investigational medicine we designed to reduce the liver production of PCSK9 and lower the plasma level of LDL-C and thus reduce the risk of cardiovascular disease;</div></td>
  </tr>
</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z2dfdbdd62d294421a7273fe5e35037c3" 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; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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;">ION532, an investigational medicine we designed to reduce the production of APOL1 for the </span>treatment of APOL1-associated chronic kidney disease;</div></td>
  </tr>
</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z0a6886f2c7d84dda9fde2a2f759cc878" 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; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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;">ION839, an investigational medicine we designed to </span>inhibit the production of PNPLA3 protein, a major genetic determinant of NASH progression<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">; and</span></div></td>
  </tr>
</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z002dc6aeb8bc422296e6d56b98c4ccce" 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; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">ION455, an investigational medicine we designed as a potential treatment for NASH.</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;">AstraZeneca is responsible for global development, regulatory and commercialization activities and costs for each of the medicines it has licensed and any medicines AstraZeneca licenses 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;">Under the terms of the agreement, we received a $65 million upfront payment. We are eligible to receive license fees and milestone payments of up to more than $5.5 billion as medicines under this collaboration advance, including up to $1.1 billion for the achievement of development milestones, up to $2.9 billion for regulatory milestones and up to $1.5 billion for commercial milestones. In addition, we are eligible to receive tiered royalties up to the low teens on net sales from any product that AstraZeneca successfully commercializes under this collaboration agreement. We will achieve the next payment of up to $30 million under this collaboration if AstraZeneca advances a medicine under this collaboration<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">.</span> From inception through December 2020, we have received over $235 million in upfront fees, license fees, milestone payments, and other payments under this collaboration, including $30 million we earned in 2020 when AstraZeneca licensed ION455 and $30 million in milestone payments we earned in 2020 when AstraZeneca advanced ION532 and ION449 in development.</div>

<div><br/></div>

<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 are recognizing revenue for our R&amp;D services performance obligation as we perform 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;"> currently estimate we will satisfy this performance obligation in</span> the third quarter of 2021. 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. From inception through December<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> 2020</span>, we have included $90 million in payments in the transaction price for our R&amp;D services performance obligation.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Under this collaboration, we have also generated additional payments that we concluded were not part of our R&amp;D services performance obligation. We recognized each of these payments in full in the respective quarter we generated the payment because the payments were distinct and we did not have any performance obligations for the respective payment. The following are the payments we have earned:</div>

<div><br/></div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z0ae7023b788a477a8ee3164fd8468aa7" 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; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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;">In the first quarter of 2018, we earned </span>two<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#160;</span>$30 million license fees when AstraZeneca licensed ION532 and ION839 because AstraZeneca had full use of the licenses without any continuing involvement from us.</div></td>
  </tr>
</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="zbd22b188d7d141118d6acbb899d46a1f" 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; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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 third quarter of 2018, we earned a $10 million milestone payment when AstraZeneca initiated a Phase 1 study of ION449.</div></td>
  </tr>
</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z8c9358f9436c4202896a2813cb0f3f39" 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; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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 fourth quarter of 2019, we earned a $10 million milestone payment when AstraZeneca initiated a Phase 1 study of ION839.</div></td>
  </tr>
</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z9a1e3b8058ca4604892bb902782a34a9" 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; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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 first quarter of 2020, we earned a $10 million milestone payment when AstraZeneca advanced ION532.</div></td>
  </tr>
</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z5a522c1fe83848f8801d15aff6f95263" 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; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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 fourth quarter of 2020, we earned a $20 million milestone payment when AstraZeneca advanced ION449.</div></td>
  </tr>
</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="zbf207a3eb3f941749b4dcfc7d039a507" 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; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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;">In the fourth quarter of 2020, we earned a </span>$30 million license fee when AstraZeneca licensed ION455 because AstraZeneca had full use of the license without any continuing involvement from us.</div></td>
  </tr>
</table>

<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;">Oncology Collaboration</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In December 2012, we entered into a collaboration agreement with AstraZeneca to discover and develop antisense medicines to treat cancer. We and AstraZeneca also established an oncology research program. AstraZeneca has the option to license medicines resulting from the program, and if AstraZeneca exercises its option to license a medicine, it will be responsible for global development, regulatory and commercialization activities and costs for such medicine. In 2020, AstraZeneca licensed ION736, an investigational medicine in development targeting FOXP3 for the treatment of cancer.</div>

<div><br/></div>

<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 this agreement, we received $</span>31<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million in upfront payments. We are eligible to receive milestone payments and license fees up to more than $</span>265<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million under this collaboration, including up to $</span>107<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million for the achievement of development milestones and up to $</span>105<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million for the achievement of regulatory milestones. 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 2020, we have received over $</span>140<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million in upfront fees, milestone payments, and other payments under this oncology collaboration, including $</span>13<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million we earned when AstraZeneca licensed</span> ION736 in 2020. We <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">will achieve the next payment of $</span>12<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">if AstraZeneca advances ION736 in development.</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 completed all of the performance obligations we identified under this collaboration in the first quarter of 2018.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Under this collaboration, we have also generated additional payments that we concluded were not part of other performance obligations discussed above. We recognized each of these payments in full in the respective quarter we generated the payment because the payments were distinct and we did not have any performance obligations for the respective payment. The following are the payments we have earned:</div>

<div><br/></div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z2bdcc0a9c35d483d9c8c7f4a41bc0cfb" 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; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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 fourth quarter of 2018, we earned a $17.5 million milestone payment and a $10 million milestone payment when AstraZeneca advanced two programs under our collaboration.</div></td>
  </tr>
</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z79487d3e861444efb73a94ea6625d8c5" 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; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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;">In the second quarter of 2020, we earned a $</span>13<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million license fee when AstraZeneca licensed ION736</span> because AstraZeneca had full use of the license without any continuing involvement from us.</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;">During the years ended December 31, 2020, 2019 and 2018, we earned the following revenue from our relationship with AstraZeneca (in millions, except percentage amounts):</div>

<div><br/></div>

<table cellpadding="0" cellspacing="0" id="z01afabad46534511a6a9d546d3508d28" 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"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/></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;">2020</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;">2019</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;">2018</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -27pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">R&amp;D revenue</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">88.0</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">28.1</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">120.7</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>
  <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;">12</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">20</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 sheet at <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">December 31, </span>2020<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> and </span>2019<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> included deferred revenue of $</span>10.0<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million and $</span>25.0<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million, respectively, related to our relationship with AstraZeneca.</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;">Bayer</div>

<div><br/></div>

<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 May 2015, we entered into an exclusive license agreement with Bayer to develop and commercialize IONIS-FXI<sub>Rx</sub> for the prevention of thrombosis. We were responsible for completing a Phase 2 study of IONIS-FXI<sub>Rx</sub> in people with end-stage renal disease on hemodialysis. Under the terms of the agreement, we received a $100 million upfront payment in the second quarter of 2015. In February 2017, we amended our agreement with Bayer to advance IONIS-FXI<sub>Rx</sub> and to initiate development of IONIS-FXI-L<sub>Rx</sub>, which Bayer licensed. In conjunction with the decision to advance these programs, we received a $75 million payment from Bayer. In October 2019, Bayer decided it would advance IONIS-FXI-L<sub>Rx</sub> following positive clinical results. Bayer is now responsible for all global development, regulatory and commercialization activities and costs for the FXI 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 are eligible to receive up to $385 million in license fees, milestone payments and other payments, including up to $125 million for the achievement of development milestones and up to $110 million for the achievement of commercialization milestones. In addition, we are eligible to receive tiered royalties in the low to high 20 percent range on gross margins of both medicines combined. From inception through December 2020, we have received over $185 million from this collaboration. We will achieve the next payment of $20 million if Bayer initiates a Phase 3 study for the FXI 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;">At the commencement of this collaboration, we identified three performance obligations, the license of IONIS-FXI<sub>Rx</sub>, R&amp;D services and delivery of API, all of which we completed in 2016.</div>

<div><br/></div>

<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 February 2017, when we amended our collaboration with Bayer, we identified two new performance obligations<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, </span>one<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> for the license of IONIS-FXI-L</span><sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> and </span>one<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> for R&amp;D services</span>. We determined the transaction price to be the $75 million payment. We allocated $64.9 million to <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">the license of IONIS-FXI-L</span><sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> based on its estimated relative stand-alone selling price and recognized the associated revenue upon our delivery of the license in the first quarter of 2017. We allocated $</span>10.1<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million to our R&amp;D services performance obligation based on an estimated relative stand-alone selling price. </span>We recognized revenue for our R&amp;D services performance obligation as we performed services based on our effort to satisfy our performance obligation relative to our total effort expected to satisfy our performance obligation. We completed our obligation in the third quarter 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;">In the fourth quarter of 2019, we earned a $10 million milestone payment when Bayer decided it would advance IONIS-FXI-L<sub>Rx</sub>. We recognized this milestone payment in full in the fourth quarter of 2019 because we did not have any performance obligations related to this milestone payment.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">During the years ended December 31, 2020, 2019 and 2018, we earned the following revenue from our relationship with Bayer (in millions, except percentage amounts):</div>

<div><br/></div>

<table cellpadding="0" cellspacing="0" id="z9c944936e6cb48bf94b3cd80005a253e" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
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    <td colspan="10" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Year Ended December 31,</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
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  <tr>
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    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2020</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <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;">2019</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;">2018</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
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    <td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -27pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">R&amp;D revenue</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3.2</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">14.3</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">5.0</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
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  <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;">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;">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;">1</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
</table>

<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Our consolidated balance sheet at December 31, </span>2020<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> did </span>no<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">t include any deferred revenue related to our relationship with Bayer. Our </span>consolidated balance sheet at <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">December 31, </span>2019<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> included deferred revenue of $</span>2.4<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million related to our relationship with Bayer.</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;">GSK</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In March 2010, we entered into an alliance with GSK using our antisense drug discovery platform to discover and develop new medicines against targets for serious and rare diseases, including infectious diseases and some conditions causing blindness. Under the terms of the agreement, we received upfront payments of $35 million. Our collaboration with GSK currently includes two medicines targeting hepatitis B virus, or HBV: IONIS-HBV<sub>Rx</sub> and IONIS-HBV-L<sub>Rx</sub>. We designed these medicines to reduce the production of viral proteins associated with HBV infection. In the third quarter of 2019, following positive Phase 2 results, GSK licensed our HBV program. GSK is responsible for all global development, regulatory and commercialization activities and costs for the HBV program.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Under our agreement, if GSK successfully develops these medicines and achieves pre-agreed sales targets, we could receive license fees and milestone payments of up to $262 million, including up to $47.5 million for the achievement of development milestones, up to $120 million for the achievement of regulatory milestones and up to $70 million for the achievement of commercialization milestones. In addition, we are eligible to receive tiered royalties up to the mid-teens on net sales from any product that GSK successfully commercializes under this alliance. From inception through December 2020, we have received more than $190 million in payments under this alliance with GSK. We will achieve the next payment of $15 million if GSK initiates a Phase 3 study of a medicine under this 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;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We completed our R&amp;D services performance obligations under our collaboration in the first quarter of 2015. </span>We identified a new performance obligation when we granted GSK the license of the HBV program and assigned related intellectual property rights in the third quarter of 2019 because the license was distinct from our other performance obligations. We recognized the $25 million license fee for the HBV program as revenue at that time because GSK had full use of the license without any continuing involvement from us. Additionally, we did not have any further performance obligations related to the license after we delivered it to GSK.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We do not have any remaining performance obligations under our collaboration with GSK; however, we can still earn additional payments and royalties as GSK advances the HBV program.</div>

<div><br/></div>

<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, 2020, 2019 and 2018, we earned the following revenue from our relationship with GSK (in millions, except percentage amounts):</div>

<div><br/></div>

<table cellpadding="0" cellspacing="0" id="zd82f932b4364444296f6727d4a1a1d5e" 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"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/></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;">2020</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;">2019</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;">2018</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -27pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">R&amp;D revenue</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.2</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">25.4</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1.6</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 64%;" valign="bottom"><div style="text-align: left; 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;">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;">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>
  </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, 2020 and 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; font-style: italic;">Janssen Biotech, 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;">In December 2014, we entered into a collaboration agreement with Janssen Biotech, Inc. to discover and develop antisense medicines that can be locally administered, including oral delivery, to treat autoimmune disorders of the GI tract. Under our collaboration, Janssen is currently advancing ION253 for the treatment of immune-mediated GI disease. Janssen licensed ION253 in the fourth quarter of 2017. Prior to Janssen&#8217;s license of ION253, we were responsible for the discovery activities to identify development candidates. Under the agreement, Janssen is responsible for global development, regulatory and commercialization activities and costs for ION253.</div>

<div><br/></div>

<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 $35 million in upfront payments. We are eligible to receive up to more than $285 million in license fees and milestone payments for these programs, including up to $65 million for the achievement of development milestones, up to $160 million for the achievement of regulatory milestones and up to $60 million for the achievement of commercialization milestones. From inception through December 2020, we have received over $80 million from this collaboration. In addition, we are eligible to receive tiered royalties up to the near teens on net sales from any medicines resulting from this collaboration. We will achieve the next payment of $5 million if Janssen continues to advance ION253 in development.</div>

<div><br/></div>

<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 Janssen. We determined the transaction price to be the $35 million upfront payments we received. We allocated the <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</span>35<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million</span> to our single performance obligation. As we achieved milestone payments for our R&amp;D services, we included these amounts in our transaction price for our R&amp;D services performance obligation. We recognized revenue for our R&amp;D services performance obligation over our period of performance, which ended in the fourth quarter of 2017.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Under this collaboration, we have also generated additional payments that we concluded were not part of our R&amp;D services performance obligation. We recognized each of these payments in full in the respective quarter in which we generated the payment because the payments were distinct and we did not have any performance obligations for the respective payment. In the third quarter of 2020, we earned a $</span>5<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million milestone payment when Janssen initiated a Phase 1 trial for ION253</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, 2020, 2019 and 2018, we earned the following revenue from our relationship with Janssen (in millions, except percentage amounts):</div>

<div><br/></div>

<table cellpadding="0" cellspacing="0" id="z214ec07483da45419ff12bf6494b6cc8" 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"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/></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;">2020</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;">2019</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;">2018</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -27pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">R&amp;D revenue</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">5.0</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-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">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6.6</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 64%;" valign="bottom"><div style="text-align: left; 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;">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;">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;">1</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
</table>

<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We did not have any deferred revenue from our relationship with Janssen at December 31, 2020 and 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; font-style: italic;">Novartis</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In January 2017, we initiated a collaboration with Novartis to develop and commercialize pelacarsen and IONIS-APOCIII-L</span><sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">.</span><sub>&#160;</sub>We received a $75 million upfront payment in the first quarter of 2017. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In the first quarter of 2019, Novartis licensed pelacarsen</span> and we earned a $150 million license fee. Novartis is responsible for conducting and funding future development and regulatory activities for pelacarsen, including a global Phase 3 cardiovascular outcomes study that Novartis initiated in the fourth quarter 2019.<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#160;</span>In connection with Novartis&#8217; license of pelacarsen, we and Novartis established a more definitive framework under which the companies would negotiate the co-commercialization of pelacarsen in selected markets. Included in this framework is an option by which Novartis could solely commercialize pelacarsen in exchange for Novartis paying us increased sales milestone payments based on sales of pelacarsen.<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#160;</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">When Novartis decided to not exercise its option for </span>IONIS-APOCIII-L<sub>Rx</sub>, we retained rights to develop and commercialize IONIS-APOCIII-L<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;">Under the collaboration, we are eligible to receive up to $675 million in milestone payments, including $25 million for the achievement of a development milestone, up to $290 million for the achievement of regulatory milestones and up to $360 million for the achievement of commercialization milestones. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">From inception through December 2020, we have received $</span>249<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million in upfront payments, milestone payments, license fees and other payments from this collaboration. </span>We are also eligible to receive tiered royalties in the mid-teens to low 20 percent range on net sales of pelacarsen. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We</span><span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> will achieve the next payment of $</span>25<span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million if Novartis advances pelacarsen.</span></div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In conjunction with this collaboration, we entered into a SPA with Novartis. As part of the SPA, Novartis purchased 1.6 million shares of our common stock for $100 million in the first quarter of 2017. As part of the SPA, Novartis was required to purchase $50 million of Akcea&#8217;s common stock at Akcea&#8217;s IPO price or our common stock at a premium if an IPO did not occur by April 2018. Under the SPA, in the second quarter of 2017, Novartis purchased $50 million of Akcea&#8217;s common stock in a separate private placement concurrent with the completion of Akcea&#8217;s IPO at a price per share equal to the IPO 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;">At the commencement of this collaboration, we identified four separate performance obligations:</div>

<div><br/></div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z96b1240939864a0aa59d9ebe41065fe9" 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; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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" id="z3d70c236552f4ba28ef26a97261216f0" 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; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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 IONIS-APOCIII-L<sub>Rx</sub>;</div></td>
  </tr>
</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="ze5c0c7016a924d6cacedb4f5ac960dfd" 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; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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" id="zdb1bac79654341e49628adcdaa4ae22a" 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; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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 IONIS-APOCIII-L<sub>Rx</sub>.</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" id="z121d185a2fd2440eb0afde6cd75e4546" 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; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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" id="zb9c0424c697141e98b124b59cc86ef6e" 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; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$28.4 million for the premium paid by Novartis for its purchase of our common stock at a premium in the first quarter of 2017; and</div></td>
  </tr>
</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z9ccebd2e3ba84fa4b417d18915d23207" 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; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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" id="zd02b83fa42c4476fa906790b9a6cedc0" 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; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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 </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">pelacarsen;</span></div></td>
  </tr>
</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z797fd60954dd4557b52fbeff3a842394" 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; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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;">IONIS-APOCIII-L</span><sub style="font-family: 'Times New Roman';">Rx</sub>; </div></td>
  </tr>
</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="zde031348d3aa4afdbd2863fd76fd398b" 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; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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><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" id="z8d4ab36eb2c14f349a1e5abf6e78ce98" 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; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">2.8</span> million for the delivery of IONIS-APOCIII-L<sub>Rx</sub> 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 recognized revenue related to each of the performance obligations as follows:</div>

<div><br/></div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z07ee17717ec44cdfadce3eff5cb75de7" 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; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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 completed our R&amp;D services performance obligation for pelacarsen<sub>&#160;</sub>in second quarter of 2019. As such, we recognized all revenue we allocated to the pelacarsen<sub>&#160;</sub>R&amp;D services as of the end of the second quarter of 2019;</div></td>
  </tr>
</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="ze87ab810b8c24867a4976ca1df80ead9" 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; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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 completed our R&amp;D services performance obligation for IONIS-APOCIII-L<sub>Rx</sub> in the fourth quarter of 2019 because Novartis elected to terminate the strategic collaboration for IONIS-APOCIII-L<sub>Rx</sub> during the period. As a result, we were not required to provide any further R&amp;D services, as such, we recognized all revenue allocated to the IONIS-APOCIII-L<sub>Rx</sub> R&amp;D services as of the end of the fourth quarter of 2019;</div></td>
  </tr>
</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z0733e5bad35c4e1399d772ddddac80e6" 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; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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 recognized the amount attributed to pelacarsen API when we delivered it to Novartis in 2017; and</div></td>
  </tr>
</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="zc5fa7220e2ed4db0afb1d000146ea46c" 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; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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 recognized the amount attributed to IONIS-APOCIII-L<sub>Rx</sub> API when we delivered it to Novartis in the second quarter of 2018.</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 recognized revenue related to the R&amp;D services for pelacarsen and IONIS-APOCIII-L</span><sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> performance obligations as we performed services </span>based on our effort to satisfy our performance obligations relative to our total effort expected to satisfy our performance obligations<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">.</span></div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">During the years ended December 31, 2020 and 2019, we earned the following revenue from our relationship with Novartis (in millions, except percentage amounts):</div>

<div><br/></div>

<table cellpadding="0" cellspacing="0" id="zbc240042123541949eac40f85586e85a" 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"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/></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;">2020</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;">2019</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;">2018</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -27pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">R&amp;D revenue</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1.0</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">187.4</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">50.6</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 64%;" valign="bottom"><div style="text-align: left; 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;">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;">17</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;">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>
  </tr>
</table>

<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We did not have any deferred revenue from our relationship with Novartis at December 31, 2020 and 2019.</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;">Pfizer</div>

<div><br/></div>

<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 October 2019, we entered into a license agreement with Pfizer for vupanorsen, an investigational medicine in development to treat people with certain cardiovascular diseases. We completed a Phase 2 study of vupanorsen in patients</span> with elevated levels of triglycerides, or hypertriglyceridemia, type 2 diabetes and <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">NAFLD. Pfizer is responsible for all global development, regulatory and commercialization activities and costs for vupanorsen, subject to our right to co-commercialize in the U.S. and certain additional markets.</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;">Under the terms of the agreement, we received a $</span>250<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million upfront payment. We are also eligible to receive development, regulatory and sales milestone payments of up to $</span>1.3<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> billion</span>, including up to $205 million for the achievement of development milestones, up to $250 million for the achievement of regulatory milestones and up to $850 million for the achievement of commercialization milestones. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">From inception through December 2020, we have received over $</span>330<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million, including a $</span>75<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million milestone payment we earned in the fourth quarter of 2020 when Pfizer began the Phase 2b study of vupanorsen. </span>We are<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> also eligible to earn tiered royalties in the mid-teens to low </span>20 percent<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> range on annual worldwide net sales. Prior to regulatory filing for marketing approval, we have the right, at our option to participate in certain commercialization activities with Pfizer in the U.S. and certain additional markets on pre-defined terms and based on meeting pre-defined criteria. 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 Pfizer advances vupanorsen.</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 the license agreement, we identified three separate performance obligations:</div>

<div><br/></div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="zd5bad646b7e448a3a9fe0f3ca3c6c245" 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; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">License of vupanorsen;</div></td>
  </tr>
</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z0f346714db2e4d08bcd013533066c0cc" 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; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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 vupanorsen; and</div></td>
  </tr>
</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="ze9f95e2f073b4cbf8e0854f2741778f8" 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; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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 vupanorsen.</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 the transaction price to be $250 million, the upfront payment we received.<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> We </span>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" id="z41311be7633d461192f4fe74ca293c01" 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; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$245.6 million for the license of vupanorsen;</div></td>
  </tr>
</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z4e228f251e304158a2d73dced6a689f4" 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; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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>2.2<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million for the R&amp;D services for </span>vupanorsen<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">; and</span></div></td>
  </tr>
</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z09d754cd2883400894b04f43113ed981" 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; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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>2.2<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million for the delivery of </span>vupanorsen<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> API.</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;">We are recognizing revenue related to each of our performance obligations as follows:</div>

<div><br/></div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z5049f3a6226d4187bf650e164ea1c247" 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; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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 recognized $245.6 million for the license of vupanorsen in the fourth quarter of 2019 because we determined the license we granted to Pfizer was distinct from our other performance obligations and Pfizer had full use of the license without any continuing involvement from us.</div></td>
  </tr>
</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z371608c9e0fe48d3a2f97c25050c0b35" 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; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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 <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">recognized revenue related to the R&amp;D services for </span>vupanorsen<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> as we performed services </span>based on our effort to satisfy our performance obligation relative to our total effort to satisfy our performance obligation<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. We completed our R&amp;D services in </span>mid-2020<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">.</span></div></td>
  </tr>
</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="zcf939c7c945446388558c20dd6e65f46" 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; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> recognized the amount attributed to the API supply for </span>vupanorsen<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> when we delivered it to Pfizer in the fourth quarter of 2019.</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;">In the fourth quarter of 2020, we earned a $75 million milestone payment when Pfizer began the Phase 2b study of vupanorsen. We recognized this milestone payment in full in the fourth quarter of 2020 because we did not have any performance obligations related to this milestone payment.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">During the years ended December 31, 2020 and 2019, we earned the following revenue from our relationship with Pfizer (in millions, except percentage amounts):</div>

<div><br/></div>

<table cellpadding="0" cellspacing="0" id="z6cd9b1a78b1f4646b6991f4b40434cd7" 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"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/></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;">2020</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;">2019</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: -27pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">R&amp;D revenue</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">82.1</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">248.7</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>
  <tr>
    <td style="vertical-align: bottom; width: 76%;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Percentage of total revenue</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">11</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">22</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;">We did </span>no<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">t have any deferred revenue from our relationship with Pfizer at December 31, </span>2020<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. Our </span>consolidated balance sheet at <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">December 31, 2019 included deferred revenue of $</span>1.3<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million related to our relationship with Pfizer.</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;">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;">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 up to $26 million in payments. From inception through December 2020, we have received $22 million from PTC. We are eligible to receive royalties from PTC in the mid-20 percent range on net sales in Latin America for each medicine. PTC&#8217;s obligation to pay us royalties begins on the earlier of 12 months after the first commercial sale of a product in Brazil or the date that PTC recognizes revenue of at least $10 million in Latin America.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In the third quarter of 2018 at the commencement of this collaboration, we identified two performance obligations, which were the licenses we granted to PTC to commercialize TEGSEDI and WAYLIVRA in Latin America and certain Caribbean countries. We recognized $12 million in license fee revenue at that time because PTC had full use of both licenses without any continuing involvement from us. We do not have any remaining performance obligations under our collaboration with PTC. We can still earn additional payments and royalties as PTC commercializes TEGSEDI and WAYLIVRA.</div>

<div><br/></div>

<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 milestone payments that we concluded were not part of the performance obligations discussed above. We recognized each of these milestone payments in full in the respective quarter in which we achieved the milestone payment because the payments were distinct and we did not have any performance obligations for the respective payment. The following are the payments we have earned:</div>

<div><br/></div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z4abce04efa244e55b617be785e66be12" 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; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In the second quarter of 2019, we earned a $6 million payment when WAYLIVRA was approved by the EMA.</div></td>
  </tr>
</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="za7c3c78f718a4ad8a301c4be154c8a67" 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; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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 fourth quarter of 2019, we earned $4 million when TEGSEDI was approved in Brazil.</div></td>
  </tr>
</table>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> </span><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">During the years ended December 31, 2020, 2019 and 2018, we earned the following revenue from our relationship with PTC (in millions, except percentage amounts):</div>

<div><br/></div>

<table cellpadding="0" cellspacing="0" id="z00af651f87dd4ff3a8aa829ed62a0b47" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
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    <td colspan="10" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Year Ended December 31,</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2020</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;">2019</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;">2018</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;">Licensing and other royalty revenue (commercial revenue)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">10.2</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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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: 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;">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;">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;">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;">Our consolidated balance sheet at December 31, 2020 and 2019 did not include any deferred revenue related to our relationship with PTC.</div>

<div><br/></div>

<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;">Roche</div>

<div><br/></div>

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

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In April 2013, we formed an alliance with Hoffman-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 in Phase 3 development. We developed tominersen through completion of our Phase 1/2 clinical study in people with early stage HD. In the fourth quarter of 2017, upon completion of the Phase 1/2 study, Roche exercised its option to license tominersen. Roche is responsible for all global development, regulatory and commercialization activities and costs for tominersen.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Under the terms of the agreement, we received an upfront payment of $30 million in April 2013 and an additional $3 million payment in 2017. We are eligible to receive up to $365 million in a license fee and milestone payments including up to $70 million for the achievement of development milestones, up to $170 million for the achievement of regulatory milestones and up to $80 million for the achievement of commercialization milestones. 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 any net sales of any product resulting from this alliance. From inception through December 2020, we have received $150 million in upfront fees, milestone payments and license fees under this collaboration. We will achieve the next payment of $15 million if Roche advances 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;">At the commencement of this collaboration, we identified one performance obligation, which was to perform R&amp;D services for Roche. We determined the transaction price to be the $30 million upfront payment we received and allocated it to our single performance obligation. As we achieved milestone payments for our R&amp;D services, we included these amounts in our transaction price for our R&amp;D services performance obligation. We recognized revenue for our R&amp;D services performance obligation over our period of performance, which ended in the third quarter of 2017.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Under this collaboration, we have also generated additional payments that we concluded were not part of our R&amp;D services performance obligation. We recognized each of these payments in full in the respective quarter in which we generated the payment because the payments were distinct and we did not have any performance obligations for the respective payment. The following are the payments we have earned:</div>

<div><br/></div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="zf451f16441ea44558aa69cebef8e1675" 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; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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 fourth quarter of 2017, we earned a $45 million license fee when Roche licensed tominersen because Roche had full use of the license without any continuing involvement from us.</div></td>
  </tr>
</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z00ac98db4efa4864b5d2fa1574c1fc7f" 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; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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 first quarter of 2019, we earned $35 million in milestone payments when Roche dosed the first patient in the Phase 3 study of tominersen in the first quarter of 2019.</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 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: justify; 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;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In October 2018, we entered into a collaboration agreement with Roche to</span><span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> develop IONIS-FB-L</span><sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> for the treatment of complement-mediated diseases. We are currently conducting Phase 2 studies in </span>two<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> disease indications for </span><span style="background-color: #FBFBFB; 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;">, </span>one<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> for the treatment of patients with GA, the advanced stage of dry AMD, and a </span><span style="-sec-ix-hidden:Fact_04500eaf787641bfbd86183ba9891b89">second</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> for the treatment of patients with IgA nephropathy. </span>Roche<span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> has the option to license 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;"> at the completion of these studies. Upon licensing, </span>Roche <span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">will be responsible for global development, regulatory and commercialization activities and 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;"><span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Under the terms of this agreement, we received a </span>$75 million<span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> upfront payment in the fourth quarter of 2018. We are eligible to receive up to </span>$684 million<span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> in development, regulatory and sales milestone payments and license fees. In addition, we are also eligible to receive tiered royalties from the high teens to </span>20 percent<span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> on net sales. We will achieve the next payment of $</span>20<span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million if we advance </span>the Phase 2 study in patients with dry AMD<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;">At the commencement of this collaboration, we identified one performance obligation, which was to perform R&amp;D services for Roche. We determined the transaction price to be the $75 million upfront payment we received and allocated it to our single performance obligation. We are recognizing revenue for our R&amp;D services performance obligation as we perform services based on our effort to satisfy our performance obligation relative to our total effort expected to satisfy our performance obligation. During the fourth quarter of 2020, we <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">updated our estimate of the total effort we expected to expend to satisfy our performance obligation under this collaboration.</span>&#160;<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In the fourth quarter of 2020, we recorded a cumulative catch up adjustment of $</span>9.2<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million to decrease revenue because we updated our total cost estimate to complete the Phase 2 study of </span><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 the </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">treatment of patients with GA. </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 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, 2020, 2019 and 2018, we earned the following revenue from our relationship with Roche (in millions, except percentage amounts):</div>

<div><br/></div>

<table cellpadding="0" cellspacing="0" id="za78565dce5c647feb8b04dec8baff53c" 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"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/></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;">2020</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;">2019</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;">2018</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -27pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">R&amp;D revenue</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">5.9</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">57.0</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">8.3</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
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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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<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 sheet at <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">December 31, </span>2020<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> and </span>2019<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> included deferred revenue of $</span>47.2<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million and $</span>52.3<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="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;">Other 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;">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 exclusively licensed to Alnylam our patent estate relating to antisense motifs and mechanisms and oligonucleotide chemistry for double-stranded RNAi therapeutics in exchange for 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 rights to 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 medicines 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;">In the fourth quarter 2020, we completed an arbitration process with Alnylam. The arbitration panel awarded us $41.2 million for payments owed to us by Alnylam related to Alnylam&#8217;s agreement with Sanofi Genzyme. We recognized the $41.2 million payment from Alnylam as revenue in the fourth quarter of 2020 because we did not have any performance obligations for the respective payment.</div>

<div><br/></div>

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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="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
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<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, 2020 and 2019 did not include any deferred revenue related to our relationship with Alnylam.</div>
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<span style="display: none;">v3.20.4</span><table class="report" border="0" cellspacing="2" id="idm140142731508168">
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<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Akcea Acquisition<br></strong></div></th>
<th class="th" colspan="1">12 Months Ended</th>
</tr>
<tr><th class="th"><div>Dec. 31, 2020</div></th></tr>
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<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_NoncontrollingInterestAbstract', window );"><strong>Akcea Acquisition [Abstract]</strong></a></td>
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<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_MinorityInterestDisclosureTextBlock', window );">Akcea Acquisition</a></td>
<td class="text">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">7. Akcea Acquisition</div>

<div><br/></div>

<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;">Purchase Price and Direct Transaction Costs Accounting for the Akcea Acquisition</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In October 2020, we acquired the shares of Akcea&#8217;s common stock we did not own, increasing our ownership from 76 percent to 100 percent. Under the purchase agreement, we purchased 24.8 million shares at $18.15 per share, resulting in a total purchase price of $450.6 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;">To reflect our 100 percent ownership, we accounted for the increase in our ownership by eliminating the noncontrolling interest adjustment in stockholders&#8217; equity in accordance with the Consolidation accounting guidance (ASC Topic 810). We recognized the difference between the purchase price and the adjustment to noncontrolling interest in stockholders&#8217; equity as additional-paid-in capital. Refer to our <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Statement of Stockholders&#8217; Equity</span> for detailed amounts.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We accounted for the transaction costs related to the Akcea Acquisition as a direct charge to stockholders&#8217; equity. We incurred $40.6 million of direct transaction costs from the Akcea Acquisition, primarily comprised of banking and legal fees.</div>

<div><br/></div>

<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;">Equity Award Payouts related to the Akcea Acquisition</div>

<div><br/></div>

<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 October 2020, as part of the Akcea Acquisition, Ionis cancelled all of Akcea&#8217;s equity awards. In exchange for the cancelled awards, if eligible under the terms of the Acquisition, we paid holder&#8217;s a cash payment. We paid $</span>18.15<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> for each outstanding RSU. For each outstanding option with an exercise price less than $</span>18.15<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, we paid $</span>18.15<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> less the exercise price. As a result, we paid out $</span>53.4<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million in the fourth quarter of 2020 related to Akcea&#8217;s cancelled equity awards. We accounted for these payments as part of the transaction costs recorded to stockholders&#8217; equity in the fourth quarter of 2020. </span>Because we did not replace the Akcea awards, we recognized all unrecognized non-cash stock-based compensation ($59.3 million) under Akcea&#8217;s Plan in our statement of operations in the post-acquisition period in the fourth quarter of 2020.</div>

<div><br/></div>

<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;">Severance and Retention Costs related to the Akcea Acquisition</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; margin-top: 2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">As a result of the Akcea Acquisition, we expect to incur severance expenses of up to $9.3 million and retention expenses of up to $19.2 million. During the fourth quarter of 2020, we recorded $15.3 million of severance and retention related costs in operating expenses. We will recognize the remaining severance and retention costs through October 2021.</div>

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; margin-top: 2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following table summarizes the costs by category related to the Akcea Acquisition (in millions):</div>

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

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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3.9</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">11.4</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></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;">15.3</div></td>
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<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; margin-top: 2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following table summarizes the severance and retention reserve included in accrued compensation for the period indicated related to Akcea Acquisition (in millions):</div>

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

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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">15.3</div></td>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(0.6</div></td>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Severance and Retention Costs related to our Restructured European Operations<br></strong></div></th>
<th class="th" colspan="1">12 Months Ended</th>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">8. Severance and Retention Costs related to our Restructured European 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;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In the fourth quarter of 2020, </span>we entered into a distribution agreement with Sobi to commercialize TEGSEDI and WAYLIVRA in Europe. Under the distribution agreement, Sobi took over all material distribution operations at the end of January 2021. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We remain the marketing authorization holder for TEGSEDI and WAYLIVRA in Europe. We will continue to maintain limited European operations including regulatory, manufacturing, and the management of relationships with key opinion leaders. We will also continue to lead the TEGSEDI and WAYLIVRA global commercial strategy.</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 a result of this change, we expect to incur up to $14.8 million of severance and retention expenses. During the fourth quarter of 2020, we recorded $12.5 million of severance and retention related costs in operating expenses related to this agreement. We will recognize the remaining expenses through October 2021, of which we will recognize the majority of the remaining expenses in the first quarter of 2021.</div>

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following table summarizes the costs by category related to our restructured European operations (in millions):</div>

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

<table cellpadding="0" cellspacing="0" id="zfc11f35900ae4dd5aad134392785c1c9" 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="text-align: left; vertical-align: bottom; 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%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>
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    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">8.3</div></td>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></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;">12.5</div></td>
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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;">The following table summarizes the severance and retention reserve included in accrued compensation for the periods indicated related to our restructured European operations (in millions):</div>

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

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    <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;">&#8212;</div></td>
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    <td style="vertical-align: top; width: 88%;" valign="bottom"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Severance &amp; retention expensed during period</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;">12.5</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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    <td style="vertical-align: top; width: 88%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Amounts paid during the period</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(0.1</div></td>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
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<span style="display: none;">v3.20.4</span><table class="report" border="0" cellspacing="2" id="idm140142733138344">
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<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Segment Information and Concentration of Business Risk<br></strong></div></th>
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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">9. Segment Information and Concentration of Business 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;">Through 2020, we had two reportable segments, our Ionis Core segment and Akcea Therapeutics. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We have provided segment financial information and results for our Ionis Core segment and our Akcea Therapeutics segment based on the segregation of revenues and expenses that our chief decision maker reviewed to assess operating performance and to make operating decisions through 2020.</span> Segment income (loss) from operations includes revenue less operating expenses attributable to each segment.</div>

<div><br/></div>

<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 Ionis Core segment, we are exploiting our antisense technology to generate a broad pipeline of first-in-class and/or best-in-class medicines for us and our partners. Our Ionis Core segment generates revenue from a multifaceted partnering strategy.</div>

<div><br/></div>

<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;">Akcea was</span> focused on developing and commercializing medicines to treat patients with serious and rare diseases<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. Akcea generated revenue from TEGSEDI and WAYLIVRA product sales and from its collaborations.</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 tables show our segment revenue and income (loss) from operations for </span>2020, 2019 and 2018<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> (in thousands), respectively.</span></div>

<div><br/></div>

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    <td colspan="1" style="vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; 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; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="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; white-space: nowrap;" valign="bottom">&#160;</td>
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    <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>
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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>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
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    <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;">&#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%; 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;">69,999</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;">&#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%; 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;">69,999</div></td>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
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    <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>
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    <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>
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    <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>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; 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%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
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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; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
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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; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">364,565</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>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
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    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">729,264</div></td>
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  </tr>
  <tr>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">563,647</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; 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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">389,575</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">(51,876</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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">901,346</div></td>
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  </tr>
  <tr>
    <td style="vertical-align: top; width: 52%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"><div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Income (loss) from operations</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">59,294</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(237,255</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
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    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">5,879</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
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    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(172,082</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><br/></div>

<table cellpadding="0" cellspacing="0" id="zd5bde97ab66c4903be53b04e577e42d6" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
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    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; 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;">Akcea Therapeutics</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
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  </tr>
  <tr>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; 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; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; 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; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; 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; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; 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; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; 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; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; 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; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 52%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="text-align: left; margin-left: 25.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">SPINRAZA royalties</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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">292,992</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">292,992</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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    <td colspan="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>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">42,253</div></td>
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  <tr>
    <td style="vertical-align: top; width: 52%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="text-align: left; margin-left: 25.2pt; 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; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
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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; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
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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; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">17,205</div></td>
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  </tr>
  <tr>
    <td style="vertical-align: top; width: 52%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"><div style="text-align: left; margin-left: 43.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total commercial revenue</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>
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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; 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>
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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; 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;">(5,583</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;">352,450</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 52%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="text-align: left; margin-left: 7.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">R&amp;D revenue under collaborative agreements</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">553,038</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">436,118</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(219,007</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">770,149</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: top; width: 52%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"><div style="text-align: left; margin-left: 25.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total segment revenue</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">858,646</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">488,543</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(224,590</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,122,599</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>
  <tr>
    <td style="vertical-align: top; width: 52%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total operating expenses</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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">523,207</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">450,469</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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(216,960</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">756,716</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 52%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"><div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Income (loss) from operations</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">335,439</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">38,074</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(7,630</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">365,883</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
</table>

<div><br/></div>

<table cellpadding="0" cellspacing="0" id="zfeba46abdf4c46b192c4196f9b159018" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td style="vertical-align: bottom; border-bottom: #000000 2px solid; white-space: nowrap;" valign="bottom"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2018</div></td>
    <td colspan="1" style="vertical-align: bottom; 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; 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%; 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;">&#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%; 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>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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%; 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>
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  <tr>
    <td style="vertical-align: top; width: 52%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="text-align: left; margin-left: 25.2pt; 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; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2,755</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">12,000</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">14,755</div></td>
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  <tr>
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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; white-space: nowrap;" valign="bottom">&#160;</td>
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    <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;">&#8212;</div></td>
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    <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>
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  <tr>
    <td style="vertical-align: top; width: 52%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="text-align: left; margin-left: 7.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">R&amp;D revenue under collaborative agreements</div></td>
    <td colspan="1" style="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="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
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  <tr>
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  </tr>
  <tr>
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    <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;">$</div></td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">295,683</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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(14,849</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">661,046</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 52%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"><div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Income (loss) from operations</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">261,732</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(230,816</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(92,288</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(61,372</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><br/></div>

<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 shows our total assets by segment at December 31, 2020 and 2019 (in thousands), respectively.</div>

<div><br/></div>

<table cellpadding="0" cellspacing="0" id="z700a3f8134a24e26a84152eb605d3867" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td style="vertical-align: bottom; border-bottom: #000000 2px solid; white-space: nowrap;" valign="bottom"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Total Assets</div></td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Ionis Core</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;">Akcea Therapeutics</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;">Elimination of</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Intercompany Activity</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;">Total</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: 52%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">December 31, 2020</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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2,792,222</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">435,824</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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(838,291</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">2,389,755</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 52%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"><div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">December 31, 2019</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3,478,081</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">599,250</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(844,219</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3,233,112</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
  </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;">Contracts receivables at December 31, 2020 was comprised of approximately 99.5percent from two significant partners. Contracts receivables at December 31, 2019 was comprised of approximately 75 percent from one significant partner.</div>
<span></span>
</td>
</tr>
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<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The entire disclosure for reporting segments including data and tables. Reportable segments include those that meet any of the following quantitative thresholds a) it's reported revenue, including sales to external customers and intersegment sales or transfers is 10 percent or more of the combined revenue, internal and external, of all operating segments b) the absolute amount of its reported profit or loss is 10 percent or more of the greater, in absolute amount of 1) the combined reported profit of all operating segments that did not report a loss or 2) the combined reported loss of all operating segments that did report a loss c) its assets are 10 percent or more of the combined assets of all operating segments.</p></div>
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<span style="display: none;">v3.20.4</span><table class="report" border="0" cellspacing="2" id="idm140142740598472">
<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, 2020</div></th></tr>
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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/></div>

<div 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 $19,500 and $26,000 in 2020 for employees under 50 years old and employees 50 years old or over, respectively. We made approximately $5.7 million, $6.4 million and $5.7 million in matching contributions for the years ended December 31, 2020, 2019 and 2018, respectively.</div>
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<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The entire disclosure for retirement benefits.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 715<br> -SubTopic 20<br> -Section 55<br> -Paragraph 17<br> -URI http://asc.fasb.org/extlink&amp;oid=118257860&amp;loc=d3e4179-114921<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 715<br> -SubTopic 20<br> -Section S99<br> -Paragraph 2<br> -URI http://asc.fasb.org/extlink&amp;oid=21916913&amp;loc=d3e273930-122802<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 715<br> -SubTopic 20<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (d)(i)<br> -URI http://asc.fasb.org/extlink&amp;oid=118255775&amp;loc=d3e1928-114920<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 715<br> -SubTopic 20<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (o)<br> -URI http://asc.fasb.org/extlink&amp;oid=118255775&amp;loc=d3e1928-114920<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 715<br> -SubTopic 20<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (p)<br> -URI http://asc.fasb.org/extlink&amp;oid=118255775&amp;loc=d3e1928-114920<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 715<br> -SubTopic 70<br> -Section 50<br> -Paragraph 1<br> -URI http://asc.fasb.org/extlink&amp;oid=49170846&amp;loc=d3e28014-114942<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 715<br> -URI http://asc.fasb.org/topic&amp;trid=2235017<br><br>Reference 8: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 715<br> -SubTopic 60<br> -Section 50<br> -Paragraph 3<br> -Subparagraph (c)<br> -URI http://asc.fasb.org/extlink&amp;oid=6414203&amp;loc=d3e39689-114964<br><br>Reference 9: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 715<br> -SubTopic 20<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (d)(iv)(03)<br> -URI http://asc.fasb.org/extlink&amp;oid=118255775&amp;loc=d3e1928-114920<br><br>Reference 10: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 715<br> -SubTopic 20<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (q)<br> -URI http://asc.fasb.org/extlink&amp;oid=118255775&amp;loc=d3e1928-114920<br><br>Reference 11: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 715<br> -SubTopic 20<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (r)(1)<br> -URI http://asc.fasb.org/extlink&amp;oid=118255775&amp;loc=d3e1928-114920<br><br>Reference 12: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 715<br> -SubTopic 20<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (d)(iii)<br> -URI http://asc.fasb.org/extlink&amp;oid=118255775&amp;loc=d3e1928-114920<br><br>Reference 13: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 715<br> -SubTopic 20<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (l)<br> -URI http://asc.fasb.org/extlink&amp;oid=118255775&amp;loc=d3e1928-114920<br><br>Reference 14: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 715<br> -SubTopic 20<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (r)(2)<br> -URI http://asc.fasb.org/extlink&amp;oid=118255775&amp;loc=d3e1928-114920<br></p></div>
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<span style="display: none;">v3.20.4</span><table class="report" border="0" cellspacing="2" id="idm140142813488120">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Legal Proceedings<br></strong></div></th>
<th class="th" colspan="1">12 Months Ended</th>
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<tr><th class="th"><div>Dec. 31, 2020</div></th></tr>
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<td class="text">&#160;<span></span>
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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>

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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 the potential loss from any legal proceeding is considered probable and the amount can be reasonably estimated, we accrue a liability for the estimated loss. Significant judgment is required to determine the probability of a loss and whether the amount of the loss is reasonably estimable. The outcome of any proceeding is not determinable in advance. As a result, the assessment of a potential liability and the amount of accruals recorded are based only on the information available to us at the time. As additional information becomes available, we reassess the potential liability related to the legal proceeding, and may revise our estimates.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">On July 16, 2020, a purported stockholder of Akcea filed an action in the Delaware Court of Chancery captioned John Makris, et al. v. Stanley T. Crooke, et al., C.A. No. 2020-0587, or the &#8220;Delaware Action.&#8221; The plaintiff in the Delaware Action asserts claims against (i) current and former members of Akcea&#8217;s board of directors; and (ii) Ionis, or collectively, the &#8220;Defendants&#8221;. The plaintiff asserts derivative claims on behalf of Akcea, which is a nominal defendant in the Delaware Action, as well as putatively direct claims on behalf of a purported class of Akcea&#8217;s stockholders. The plaintiff in the Delaware action asserts that the Defendants breached their fiduciary duties in connection with the licensing transaction that we and Akcea entered into regarding TEGSEDI and IONIS-TTR-L</span><sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. The plaintiff also asserts an unjust enrichment claim against Ionis. The plaintiff&#8217;s claims are similar to those asserted in a prior action in the Delaware Court of Chancery captioned City of Cambridge Retirement System v. Crooke, et al., C.A. No. 2019-0905, which was dismissed with prejudice to the named plaintiff only on April 8, 2020. We believe that the claims asserted in the Delaware Action are without merit and anticipate filing a motion to dismiss the claims.</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;">In light of the August 31, 2020 public announcement of the Akcea Acquisition, the parties to the Delaware Action entered into a stipulation whereby the Defendants need to respond to the complaint filed on July 16, 2020, and the plaintiff will file an amended complaint. The amended complaint has not yet been filed.</span></div>
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<span style="display: none;">v3.20.4</span><table class="report" border="0" cellspacing="2" id="idm140142731255592">
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<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Fourth Quarter Financial Data (Unaudited)<br></strong></div></th>
<th class="th" colspan="1">12 Months Ended</th>
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<tr><th class="th"><div>Dec. 31, 2020</div></th></tr>
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<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_QuarterlyFinancialInformationDisclosureAbstract', window );"><strong>Fourth Quarter Financial Data (Unaudited) [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="top.Show.showAR( this, 'defref_us-gaap_QuarterlyFinancialInformationTextBlock', window );">Fourth Quarter Financial Data (Unaudited)</a></td>
<td class="text">
<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/></div>

<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 2020 and 2019 are as follows (in thousands, except per share data).</div>

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<table cellpadding="0" cellspacing="0" id="zb2695825d71444f0828c50eac6305221" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td style="vertical-align: bottom; border-bottom: #000000 2px solid;" valign="bottom"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Three Months Ended December 31,</div></td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2020</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;">2019</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Revenue</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">290,281</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">493,680</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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    <td style="vertical-align: bottom; width: 76%;" valign="bottom"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Operating expenses</div></td>
    <td colspan="1" 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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">312,945</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">233,028</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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    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Income (loss) from operations</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(22,664</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">260,652</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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    <td style="vertical-align: bottom; width: 76%;" valign="bottom"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net income (loss)</div></td>
    <td colspan="1" 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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(341,426</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">203,957</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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    <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 income (loss) attributable to Ionis Pharmaceuticals, Inc. common stockholders</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(340,271</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">184,415</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;">Basic net income (loss) per share (1) (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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(2.44</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">1.31</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;">Diluted net income (loss) per share (1) (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"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(2.44</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1.28</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: 10pt;">________________</div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z95fc0fe83dcc44d3beffd99343c41418" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
  <tr>
    <td style="width: 36pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(1)</td>
    <td style="width: auto; vertical-align: top; text-align: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We </span>compute net income (loss) per share independently for each quarter during <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">the year.</span></div></td>
  </tr>
</table>

<div><br/></div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z7f159b28bab545f4b7ef06cc58aafa2d" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
  <tr>
    <td style="width: 36pt; vertical-align: top; align: right; 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;">As discussed in Note 1, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Organization and Significant Accounting Policies, </span>we compute basic net income (loss) per share by dividing the total net income (loss) attributable to our common stockholders by our weighted-average number of common shares outstanding during the period. Our basic net income (loss) per share calculation for each of the fourth quarters in 2020 and 2019 considered our net income (loss) for Ionis on a stand-alone basis plus our share of Akcea&#8217;s net loss for the period. To calculate the portion of Akcea&#8217;s net loss attributable to our ownership, we multiplied Akcea&#8217;s loss per share by the weighted average shares we owned in Akcea during the period. As a result of this calculation, our total net income (loss) available to Ionis common stockholders for the calculation of net income (loss) per share is different than net income (loss) attributable to Ionis Pharmaceuticals, Inc. common stockholders in the consolidated statements of operations.</div></td>
  </tr>
</table>

<div><br/></div>

<div style="text-align: justify; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our basic net income (loss) per share the quarter referenced was calculated as follows (in thousands, except per share amounts):</div>

<div><br/></div>

<table cellpadding="0" cellspacing="0" id="z575ab3fcea8448b08361487272ec926a" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td style="vertical-align: bottom; border-bottom: #000000 2px solid; white-space: nowrap;" valign="bottom"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Three Months Ended December 31 , 2020</div></td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Weighted</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Average Shares</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Owned in Akcea</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Akcea</span>&#8217;<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">s</span></div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Net Loss</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Per Share</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Basic Net Loss</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Per Share</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Calculation</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Akcea&#8217;s net loss in the pre-acquisition period attributable to our ownership</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">77,095</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(0.05</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">(3,603</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>
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    <td style="vertical-align: top; width: 64%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Akcea&#8217;s net loss in the post-acquisition period attributable to our ownership</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
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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">&#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; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
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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; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
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  <tr>
    <td style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net loss available to Ionis common stockholders</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
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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>
  </tr>
  <tr>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">139,956</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Basic net loss per share</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
</table>

<div><br/></div>

<table cellpadding="0" cellspacing="0" id="z4d63d8880724435496c59a8fec3d2f7e" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td style="vertical-align: bottom; border-bottom: #000000 2px solid; white-space: nowrap;" valign="bottom"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Three Months Ended December 31 , 2019</div></td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
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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; white-space: nowrap;" valign="bottom">&#160;</td>
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    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.87</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">62,243</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: top; width: 64%; white-space: nowrap;" valign="bottom"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Akcea&#8217;s net income attributable to our ownership</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">&#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%; 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">&#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%; white-space: nowrap;" 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: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Ionis&#8217; stand-alone net income</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">121,552</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: top; width: 64%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net income available to Ionis common stockholders</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
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  </tr>
  <tr>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
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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: top; width: 64%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Basic net income per share</div></td>
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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; text-align: right; width: 9%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
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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>
  </tr>
</table>

<div><br/></div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z24e5fa74899b4127901c49f6468fa415" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
  <tr>
    <td style="width: 36pt; vertical-align: top; align: right; 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;">We had net income available to Ionis common stockholders for the fourth quarter of 2019. As a result, we computed diluted net income per share using the weighted-average number of common shares and dilutive common equivalent shares outstanding during the period as follows (in thousands except per share amounts):</div></td>
  </tr>
</table>

<div><br/></div>

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  <tr>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Per-Share</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Amount</div></td>
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  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net income available to Ionis common stockholders</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">183,795</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">140,583</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">1.31</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Effect of dilutive securities:</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 21pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Shares issuable upon exercise of stock options</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,467</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 21pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Shares issuable upon restricted stock award issuance</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">848</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 21pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Shares issuable related to our ESPP</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">18</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 21pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Shares issuable related to our 0.125 percent convertible notes</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">644</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;">860</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 21pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Shares issuable related to our 1 percent convertible notes</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;">12,046</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;">9,527</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">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; padding-bottom: 4px;" valign="bottom"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Income available to Ionis common stockholders, plus assumed conversions</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" 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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">196,485</div></td>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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<span style="display: none;">v3.20.4</span><table class="report" border="0" cellspacing="2" id="idm140142735567160">
<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>
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<tr><th class="th"><div>Dec. 31, 2020</div></th></tr>
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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="top.Show.showAR( this, 'defref_us-gaap_ConsolidationPolicyTextBlock', window );">Basis of Presentation</a></td>
<td class="text">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Basis of Presentation</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In our consolidated financial statements we included the accounts of Ionis Pharmaceuticals, Inc. and the consolidated results of our subsidiary, Akcea Therapeutics, Inc. and its wholly owned subsidiaries (&#8220;we&#8221;, &#8220;us&#8221; or &#8220;our&#8221;). We formed Akcea in December 2014. In July 2017, Akcea completed an initial public offering, or IPO. Prior to Akcea&#8217;s IPO in July 2017, we owned </span>100 percent<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> of Akcea. In October 2020, we acquired the shares of Akcea&#8217;s common stock we did not own. We will refer to this transaction as the Akcea Acquisition throughout the remainder of this document. </span>See Note 7, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Akcea Acquisition</span>, in the Notes to the Consolidated Financial Statements for further details.<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> We reflected changes in our ownership percentage in our financial statements as an adjustment to noncontrolling interest in the period the change occurred.</span></div>
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<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_EarningsPerSharePolicyTextBlock', window );">Basic and Diluted Net Income (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 Income (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 income (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 income (loss) per share by dividing the total net income (loss) attributable to our common stockholders 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;">The calculation of total net income (loss) attributable to our common stockholders for each year considered our net income (loss) for Ionis on a stand-alone basis plus our share of Akcea&#8217;s net income (loss) for the period. To calculate the portion of Akcea&#8217;s net income (loss) attributable to our ownership for each year, we multiplied Akcea&#8217;s income (loss) per share by the weighted average shares we owned in Akcea during the period. As a result of this calculation, our total net income (loss) available to Ionis common stockholders for the calculation of net income (loss) per share is different than net income (loss) attributable to Ionis Pharmaceuticals, Inc. common stockholders in our consolidated statements of operations for each 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;">Our basic net income (loss) per share was calculated as follows (in thousands, except per share amounts):</div>

<div><br/></div>

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    <td style="vertical-align: bottom; border-bottom: #000000 2px solid; white-space: nowrap;" valign="bottom"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Year Ended December 31, 2020</div></td>
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    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Akcea</span>&#8217;<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">s</span></div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Net Loss</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Per Share</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Basic Net Loss</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Per Share</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Calculation</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">77,095</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(1.45</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(111,775</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
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  <tr>
    <td style="vertical-align: top; width: 64%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Akcea&#8217;s net loss in the post-acquisition period attributable to our ownership</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(85,987</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
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    <td style="vertical-align: top; width: 64%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Akcea&#8217;s total net loss attributable to our ownership</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(197,762</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Ionis&#8217; stand-alone net loss</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(253,725</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net loss available to Ionis common stockholders</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
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  <tr>
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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; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
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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; 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>
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  </tr>
  <tr>
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</table>

<div><br/></div>

<table cellpadding="0" cellspacing="0" id="z7190f4cfc9904c35afaf55ca55271bf2" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
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  <tr>
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    <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>
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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"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.49</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">34,073</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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    <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">&#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%; 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">&#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%; white-space: nowrap;" valign="bottom">&#160;</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; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">34,073</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: 64%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Ionis&#8217; stand-alone net income</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">262,490</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>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net income available to Ionis common stockholders</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></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>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Weighted average shares outstanding</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">139,998</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: top; width: 64%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Basic net income per share</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" 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; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2.12</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
</table>

<div><br/></div>

<table cellpadding="0" cellspacing="0" id="zc4df006abbbb4d5b9a0a303fb389d2b3" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
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    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Basic Net Income</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Per Share</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Calculation</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Common shares</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>
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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"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(2.74</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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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: top; width: 64%; white-space: nowrap;" valign="bottom"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Akcea&#8217;s net loss attributable to our ownership</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">&#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%; 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">&#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%; white-space: nowrap;" valign="bottom">&#160;</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; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(163,938</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: 64%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Ionis&#8217; stand-alone net income</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">440,806</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: top; width: 64%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net income available to Ionis common stockholders</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times 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; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">276,868</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Weighted average shares outstanding</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">132,320</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: top; width: 64%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Basic net income per share</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2.09</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; font-style: italic;">Diluted net income 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 year ended December 31, 2020, we incurred a net loss; therefore, we did not include dilutive common equivalent shares in the computation of diluted net loss per share because the effect would have been anti-dilutive. Common stock from the following would have had an anti-dilutive effect on net loss per share:</div>

<div><br/></div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="za661525f8bef42ea9eb273beec8c3ffa" 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; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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;</span></div></td>
  </tr>
</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="zcb135ba690824483aa0fa909f89a6a2a" 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; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1 percent<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> convertible senior notes;</span></div></td>
  </tr>
</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="zd9638f50b7c74568a481c388188fcd9b" 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; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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" id="zbac81e814d3144cfb944e6b840054211" 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; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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; and</div></td>
  </tr>
</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="za8f44a91052a49768a8cab1258c98733" 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; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">For the years ended December 31, 2019 and 2018, we had net income available to Ionis common stockholders. As a result, we computed diluted net income per share using the weighted-average number of common shares and dilutive common equivalent shares outstanding during each period.</span> We calculated our diluted net income per share as follows <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(in thousands except per share amounts):</span></div>

<div><br/></div>

<table cellpadding="0" cellspacing="0" id="zbebb8966d0bf411b9c7f046d05640cb2" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td style="vertical-align: bottom; border-bottom: #000000 2px solid;" valign="bottom"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Year Ended December 31, 2019</div></td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Income</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(Numerator)</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Shares</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(Denominator)</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Per-Share</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Amount</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net income available to Ionis common stockholders</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
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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="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>
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    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
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  <tr>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>
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<div><br/></div>

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    <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; 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>
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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%;" 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>
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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>
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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">&#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>
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    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
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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">&#160;</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>
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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="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>
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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%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; padding-bottom: 4px;" 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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">276,868</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">134,056</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">2.07</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>

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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">For each year presented, the calculation excluded our convertible senior notes because the effect on diluted earnings per share was anti-dilutive.</div>
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<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerPolicyTextBlock', window );">Revenue Recognition</a></td>
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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Revenue Recognition</div>

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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-decoration: underline;">Our Revenue Sources</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 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 in deferred revenue on our consolidated balance sheet.</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;">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 will also recognize as commercial revenue sales milestone payments and royalties we earn under our other partnerships.</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;">Commercial Revenue: Product sales, 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 added product sales from TEGSEDI to our commercial revenue in the fourth quarter of 2018 and we added product sales from WAYLIVRA to our commercial revenue in the third quarter of 2019. </span>In the U.S., we distribute TEGSEDI through an exclusive distribution agreement with a third-party logistics company, or 3PL, that takes title to TEGSEDI. The 3PL is our sole customer in the U.S. The 3PL then distributes TEGSEDI to a specialty pharmacy and a specialty distributor, which we collectively refer to as wholesalers, who then distribute TEGSEDI to health care providers and patients.</div>

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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In Europe, through 2020 we sold TEGSEDI and WAYLIVRA to hospitals and pharmacies using 3PLs as distributors. Beginning in 2021, we are commercializing TEGSEDI and WAYLIVRA in Europe through a distribution agreement with Swedish Orphan Biovitrum AB, or Sobi, an international biopharmaceutical company that focuses on rare diseases. Under the terms of this agreement, we retained the marketing authorization for both medicines 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;">In Latin America beginning in 2020, we sold TEGSEDI and WAYLIVRA to our partner, PTC Therapeutics. Under our collaboration agreement with PTC, PTC is commercializing TEGSEDI and WAYLIVRA in Latin America and Caribbean countries.</div>

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<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Research and development revenue under collaborative agreements</div>

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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We often 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, research and development, or R&amp;D, services, and manufacturing services.</div>

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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We provide details about our collaboration agreements in Note 6, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Collaborative Arrangements and Licensing Agreements.</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">&#160;</span>Under each collaboration note we discuss our specific revenue recognition conclusions, including our significant performance obligations under each collaboration.</div>

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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-decoration: underline;">Steps to Recognize Revenue</span></div>

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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We use a five-step process to determine the amount of revenue we should recognize and when we should recognize it. The five step process is as follows:</div>

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    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">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; font-weight: bold;">Identify the contract</div></td>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Accounting rules require us to first determine if we have a contract with our partner, including confirming that we have met each of the following criteria:</div>

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    <td style="width: 36pt;"/>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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 style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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 cellpadding="0" cellspacing="0" class="DSPFListTable" id="zca7ebdde125e410485d2be933fa84a5b" 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; align: right;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; font-style: italic;">2</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold; font-style: italic;">.</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; font-weight: bold;">Identify the performance obligations</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 next identify our performance obligations, which represent the distinct goods and services we are required to provide under the contract. We typically have only one performance obligation at the inception of a contract, which is to perform R&amp;D services.</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;">Often we enter into a collaboration agreement in which we provide our partner with an option to license a medicine in the future. We may also provide our partner with an option to request that we provide additional goods or services in the future, such as active pharmaceutical ingredient, or API. We evaluate whether these options are material rights at the inception of the agreement. If we determine an option is a material right, we will consider the option a separate performance obligation. Historically, we have concluded that the options we grant to license a medicine in the future or to provide additional goods and services as requested by our partner are not material rights because these items are contingent upon future events that may not occur and are not priced at a significant discount. When a partner exercises its option to license a medicine or requests additional goods or services, then we identify a new performance obligation for that item</span>.</div>

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<div 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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<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z89d2a19ad3fd4d87aa3b3cc055a6b623" 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; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">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; font-weight: bold;">Determine the transaction price</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 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 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;">Milestone payments are our most common type of variable consideration. We recognize milestone payments using the most likely amount method because we will either receive the milestone payment or we will not, which makes the potential milestone payment a binary event. The most likely amount method requires us to determine the likelihood of earning the milestone payment. We include a milestone payment in the transaction price once it is probable we will achieve the milestone event. Most often, we do not consider our milestone payments probable until we or our partner achieve the milestone event because the majority of our milestone payments are contingent upon events that are not within our control and/ or are usually based on scientific progress which is inherently uncertain. For example, in the </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">fourth</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> quarter of </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">2020</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, we earned</span> a $20 million <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">milestone payment from AstraZeneca when AstraZeneca initiated a Phase </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">2</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">b study for ION</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">449</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, our medicine in development targeting PCSK</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">9</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> to lower LDL-cholesterol. We did not consider the milestone payment probable until AstraZeneca achieved the milestone event because advancing ION</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">449</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> was contingent on AstraZeneca initiating a Phase </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">2</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">b study and was not within our control. We recognized the milestone payment in full in the period the milestone event was achieved because we did not have any remaining performance obligations related to the milestone payment</span>.</div>

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    <td style="width: 36pt;"/>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">4.</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; font-weight: bold;">Allocate the transaction price</div></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;"><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 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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  <tr>
    <td style="width: 36pt;"/>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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>
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<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z10d63e5de2314c06ad22cc7840776d39" 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; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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>
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<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="zba714425a66248a085047d1335e5f538" 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; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Estimated contractual milestone payments we may receive;</div></td>
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<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="zbd24a106c9494a478e217043fc30b768" 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; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Expenses we expect to incur;</div></td>
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    <td style="width: 36pt;"/>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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 cellpadding="0" cellspacing="0" class="DSPFListTable" id="z55a0f09a57a440e78616543b799da651" 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; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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>
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<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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<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="zb8283a4050434163907eb1ceed915b35" 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; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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 number of internal hours we estimate we will spend performing these services;</div></td>
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<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z1836887ec24a41eab911e7b298d0794f" 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; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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 cellpadding="0" cellspacing="0" class="DSPFListTable" id="z00a44e034e0c47d3bd2e75356a388f81" 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; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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 cellpadding="0" cellspacing="0" class="DSPFListTable" id="z3ae90bb9080943f2b46aad96c46d875e" 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; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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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<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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<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="ze208c18727bc49289f50b3daf6d37408" 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; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">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; font-weight: bold;">Recognize revenue</div></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;">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 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;">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.</span> Refer to Note 6, <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 the cumulative catch up adjustment we made.</div>

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<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following are examples of when we typically recognize revenue based on the types of payments we receive.</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="text-decoration: underline;">Commercial Revenue: SPINRAZA royalties and Licensing and other royalty revenue</span></div>

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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We recognize royalty revenue, including royalties from SPINRAZA sales, in the period in which the counterparty sells the related product and recognizes the related revenue, which in certain cases may require us to estimate our royalty revenue</span>.</div>

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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><span style="text-decoration: underline;">Commercial Revenue: Product sales, net</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 recognize product sales in the period when our customer obtains control of our products, which occurs at a point in time upon transfer of title to the customer. We classify payments to customers or other parties in the distribution channel for services that are distinct and priced at fair value as selling, general and administrative, or SG&amp;A, expenses in our consolidated statements of operations. Otherwise, payments to customers or other parties in the distribution channel that do not meet those criteria are classified as a reduction of revenue, as discussed further below. We exclude from revenues taxes collected from customers relating to product sales and remitted to governmental authorities</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;">Reserves for Product sales</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 record product sales at our net sales price, or transaction price. We include in our transaction price estimated reserves for discounts, returns, chargebacks, rebates and other allowances that we offer within contracts between us and our customers, wholesalers, health care providers and other indirect customers. We estimate our reserves using the amounts we have earned or what we can claim on the associated sales. We classify our reserves as a reduction of accounts receivable when we are not required to make a payment or as a current liability when we are required to make a payment. In certain cases, our estimates include a range of possible outcomes that are probability weighted for relevant factors such as our historical experience, current contractual and statutory requirements, specific known market events and trends, industry data and forecasted customer buying and payment patterns. Overall, our reserves reflect our best estimates under the terms of our respective contracts. When calculating our reserves and related product sales, we only recognize amounts to the extent that we consider it probable that we would not have to reverse in a future period a significant amount of the cumulative sales we previously recognized. The actual amounts we receive may ultimately differ from our reserve estimates. If actual amounts in the future vary from our estimates, we will adjust these estimates, which would affect our net product sales in the respective period</span>.</div>

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<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following are the components of variable consideration related to product sales:</div>

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<div style="text-align: justify; margin-left: 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;">Chargebacks: </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In the U.S., we estimate obligations resulting from contractual commitments with the government and other entities to sell products to qualified healthcare providers at prices lower than the list prices charged to our U.S. customer. Our U.S. customer charges us for the difference between what it pays for the product and the selling price to the qualified healthcare providers. We also estimate the amount of chargebacks related to our estimated product remaining in the distribution channel at the end of the reporting period that we expect our customer to sell to healthcare providers in future periods. We record these reserves as a reduction to contracts receivable on our consolidated balance sheet</span>.</div>

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<div style="text-align: justify; margin-left: 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;">Government rebates</span><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;">We are subject to discount obligations under government programs, including Medicaid and Medicare programs in the U.S. and we record reserves for government rebates based on statutory discount rates and estimated utilization. We estimate Medicaid and Medicare rebates based on a range of possible outcomes that are probability weighted for the estimated payer mix. We record these reserves as an accrued liability on our consolidated balance sheet with a corresponding offset reducing our product sales in the same period we recognize the related sale. For Medicare, we also estimate the number of patients in the prescription drug coverage gap for whom we will owe an additional liability under the Medicare Part D program. On a quarterly basis, we update our estimates and record any adjustments in the period that we identify the adjustments</span>.</div>

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<div style="text-align: justify; margin-left: 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;">Managed care rebates: </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We are subject to rebates in connection with agreements with certain contracted commercial payers. We record these rebates as a liability on our consolidated balance sheet in the same period we recognize the related revenue. We estimate our managed care rebates based on our estimated payer mix and the applicable contractual rebate rate</span>.</div>

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<div style="text-align: justify; margin-left: 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;">Trade discounts: </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We provide customary invoice discounts on product sales to our U.S. customer for prompt payment. We record this discount as a reduction of product sales in the period in which we recognize the related product revenue</span>.</div>

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<div style="text-align: justify; margin-left: 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;">Distribution services</span>: <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We receive and pay for various distribution services from our U.S. and European customers (prior to our agreement with Sobi) and wholesalers in the U.S. We classify the costs for services we receive that are either not distinct from the sale of the product or for which we cannot reasonably estimate the fair value as a reduction of product sales. To the extent that the services we receive are distinct from the sale of the product, we classify the costs for such services as SG&amp;A expenses.</span></div>

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<div style="text-align: justify; margin-left: 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;">Product returns: </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Our U.S. customer has return rights and the wholesalers have limited return rights primarily related to the product&#8217;s expiration date. We estimate the amount of product sales that our customer may return. We record our return estimate as an accrued refund liability on our consolidated balance sheet with a corresponding offset reducing our product sales in the same period we recognize the related sale. Based on our distribution model for product sales, contractual inventory limits with our customer and wholesalers and the price of the product, we have had minimal returns to date and we believe we will continue to have minimal returns in the U.S. Our European customers generally only take title to the product after they receive an order and therefore they do not maintain excess inventory levels of our products. Accordingly, we have limited return risk in Europe and we do not estimate returns in Europe</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;"><span style="text-decoration: underline;">Research and development revenue under collaboration agreements:</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;"><span style="text-decoration: underline;">Upfront payments</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;">When we enter into a collaboration agreement with 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. For example, under our collaboration agreement with Roche to</span><span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> develop IONIS-FB-L</span><sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> for the treatment of complement-mediated diseases, we received a $</span>75<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million upfront payment in the fourth quarter of 2018. We allocated the upfront payment to our single performance obligation, R&amp;D services. We are amortizing the $</span>75<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million upfront payment using an input method over the estimated period of time we are providing 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; font-style: italic;"><span style="text-decoration: underline;">Milestone payments</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 are required to include additional consideration in the transaction price when it is probable. We typically include milestone payments for R&amp;D services in the transaction price when they are achieved. We include these milestone payments when they are achieved because typically there is considerable uncertainty in the research and development processes that trigger these payments. Similarly, we include approval milestone payments in the transaction price once the medicine is approved by the applicable regulatory agency. We will recognize sales-based milestone payments in the period in which we achieve the milestone under the sales-based royalty exception allowed under accounting rules.</div>

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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We recognize milestone payments that relate to an ongoing performance obligation over our period of performance. For example, in the </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">fourth</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> quarter of </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">2020</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, we achieved a</span> $7.5&#160;<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">million milestone payment from Biogen when we advanced</span>&#160;<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">a </span>target under our 2018 strategic collaboration.<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> We added this payment to the transaction price and allocated it to our R&amp;D services performance obligation. We are recognizing revenue related to this milestone payment over our estimated period of performance</span>.</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. For example, in the third quarter of 2020, we recognized $18 million in milestone payments when Biogen initiated a Phase 1/2 trial for <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">ION464, our medicine in development targeting alpha-synuclein to treat patients with multiple system atrophy</span>. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We concluded that the milestone payments were not related to our R&amp;D services performance obligation. Therefore, we recognized the milestone payments in full in the third quarter of 2020.</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;"><span style="text-decoration: underline;">License fees</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 generally recognize as revenue the total amount we determine to be the relative stand-alone selling price of a license when we deliver the license to our partner. This is because our partner has full use of the license and we do not have any additional performance obligations related to the license after delivery. For example, in the </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">fourth</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> quarter of </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">2020</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, we earned a</span> $30&#160;<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">million license fee from AstraZeneca when AstraZeneca licensed ION</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">455</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, an investigational medicine in development to treat nonalcoholic steatohepatitis, or 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; font-style: italic;"><span style="text-decoration: underline;">Sublicense fees</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 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>For example, in the fourth quarter of 2020, we earned a $41.2 million sublicense fee from Alnylam Pharmaceuticals for its sublicense of our technology to Sanofi Genzyme.</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;">Amendments to Agreements</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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<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="zc5f99d759c1848d881070e04e6c73535" 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; align: right; 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 cellpadding="0" cellspacing="0" class="DSPFListTable" id="z64fa57d8d257481ab6fc670c67d5e2dc" 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; align: right; 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 at a stand-alone selling price.</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 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 adjustment.</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;">For example, in May 2015, we entered into an exclusive license agreement with Bayer to develop and commercialize IONIS-FXI</span><sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> for the prevention of thrombosis. As part of the agreement, Bayer paid us a $</span>100<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million upfront payment. At the onset of the agreement, we were responsible for completing a Phase 2 study of IONIS-FXI</span><sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> in people with end-stage renal disease on hemodialysis and for providing an initial supply of API. In February 2017, we amended our agreement with Bayer to advance IONIS-FXI</span><sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> and to initiate development of IONIS-FXI-L</span><sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, which Bayer licensed. As part of the 2017 amendment, Bayer paid us $</span>75<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million. We are also eligible to receive milestone payments and tiered royalties on gross margins of IONIS-FXI</span><sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> and IONIS-FXI-L</span><sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. Under the 2017 amendment, we concluded we had a new agreement with </span>three<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> performance obligations. These performance obligations were to deliver the license of IONIS-FXI-L</span><sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, to provide R&amp;D services and to deliver API. We allocated the $</span>75<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million transaction price to these performance obligations. Refer to Note 6, </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Collaborative Arrangements and Licensing Agreements</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, </span>in our audited financial statements included in our Annual Report on Form 10-K for the year ended December 31, 2019 <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">for further discussion of the Bayer 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;">Multiple agreements</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;">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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<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z4eb4c38c616c425ca052b7ee9921b301" 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; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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>
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<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z791c1b1e598245bfadb2be27fb53a91f" 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; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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>
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<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="zca4b2c0359fd49008d64fab4cf31367c" 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; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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="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>

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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 example, in the second quarter of 2018, we entered into two separate agreements with Biogen at the same time: <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">a new strategic neurology collaboration agreement and a stock purchase agreement, or SPA. We evaluated the Biogen agreements to determine whether we should treat the agreements separately or combine them. We considered that the agreements were negotiated concurrently and in contemplation of </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">one</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> another. Based on these facts and circumstances, we concluded that we should evaluate the provisions of the agreements on a combined basis</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">.</span></div>
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<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ReceivablesPolicyTextBlock', window );">Contracts Receivable</a></td>
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<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>

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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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<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_TradeAndOtherAccountsReceivableUnbilledReceivablesPolicy', window );">Unbilled SPINRAZA Royalties</a></td>
<td class="text">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: -54pt; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Unbilled SPINRAZA 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;">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 on our consolidated balance sheet.</div>
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<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueRecognitionPolicyTextBlock', window );">Deferred Revenue</a></td>
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<div style="text-align: left; text-indent: -54pt; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Deferred Revenue</div>

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<div style="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 on our consolidated balance sheet.</span> During the years ended December 31, 2020 and 2019, we recognized $100.4 million and $159.5 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>
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<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_CostOfSalesPolicyTextBlock', window );">Cost of Products Sold</a></td>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Cost of Products Sold</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 products sold includes 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 products sold. Prior to obtaining regulatory approval of TEGSEDI in July 2018 and WAYLIVRA in May 2019, we expensed as research and development expenses a significant portion of the costs we incurred to produce the initial commercial launch supply for each medicine.</div>
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<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ResearchAndDevelopmentExpensePolicy', window );">Research and Development Expenses</a></td>
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<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our research and development expenses include wages, benefits, facilities, supplies, external services, clinical trial and manufacturing costs and other expenses that are directly related to our research and development operations. We expense research and development costs as we incur them. When we make payments for research and development services prior to the services being rendered, we record those amounts as prepaid assets on our consolidated balance sheet and we expense them as the services are provided. For the years ended December 31, 2020, 2019 and 2018, research and development expenses were $531.0 million, $461.5 million and $411.9 million, respectively. A portion of the costs included in research and development expenses are costs associated with our partner agreements. For the years ended December 31, 2020, 2019 and 2018, research and development costs of approximately $49.8 million, $83.2 million and $58.7 million, respectively, were related to our partner agreements.</div>
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<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_IntangibleAssetsFiniteLivedPolicy', window );">Patent Expenses</a></td>
<td class="text">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We capitalize costs consisting principally of outside legal costs and filing fees related to obtaining patents. We amortize patent costs over the useful life of the patent, beginning with the date the U.S. Patent and Trademark Office, or foreign equivalent, issues the patent. The weighted average remaining amortizable life of our issued patents was 10.3 years at December 31, 2020.</div>

<div><br/></div>

<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 cost of our patents capitalized on our consolidated balance sheet at December 31, 2020 and 2019 was $37.0 million and $34.0 million, respectively. Accumulated amortization related to patents was $9.1 million and $8.3 million at December 31, 2020 and 2019, 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;">Based on our existing patents, we estimate amortization expense related to patents in each of the next five years to be the following:</div>

<div><br/></div>

<table cellpadding="0" cellspacing="0" id="z1566f0aad503425294fc597dc5e10f73" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td style="vertical-align: bottom; border-bottom: #000000 2px solid;" valign="bottom"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Year Ending December 31,</div></td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Amortization</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(in millions)</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
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    <td style="vertical-align: bottom; width: 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;">2021</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2.1</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
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    <td style="vertical-align: bottom; width: 88%;" valign="bottom"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2022</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">2.0</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; 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;">2023</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1.9</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 88%;" valign="bottom"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2024</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">1.7</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: 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;">2025</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1.6</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
</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 review our capitalized patent costs regularly to ensure that they include costs for patents and patent applications that have future value. When we identify patents and patent applications that we are not actively pursuing, we write off any associated costs. In 2020, 2019 and 2018, patent expenses were $4.1 million, $4.2 million and $2.6 million, respectively, and included non-cash charges related to the write-down of our patent costs to their estimated net realizable values of $1.9 million, $2.2 million and $0.8 million, respectively.</div>
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<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ConsolidationSubsidiariesOrOtherInvestmentsConsolidatedEntitiesPolicy', window );">Noncontrolling Interest in Akcea Therapeutics, Inc.</a></td>
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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Noncontrolling Interest in Akcea Therapeutics, Inc.</div>

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<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Since Akcea&#8217;s IPO in July 2017 and prior to the Akcea Acquisition in October 2020, the shares of Akcea&#8217;s common stock third parties owned represented an interest in Akcea&#8217;s equity that we did not control. During this period our ownership ranged from </span>68 percent<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> to </span>77 percent<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. However, as we maintained overall control of Akcea through our voting interest, we reflected the assets, liabilities and results of operations of Akcea in our consolidated financial statements. Since Akcea&#8217;s IPO in July 2017 and through the closing of the Akcea Acquisition, we reflected the noncontrolling interest attributable to other owners of Akcea&#8217;s common stock on a separate line on our statement of operations and a separate line within stockholders&#8217; equity in our consolidated balance sheet. In addition, through the closing of the Akcea Acquisition, we recorded a noncontrolling interest adjustment to account for the stock options Akcea granted, which if exercised, would have diluted our ownership in Akcea. This adjustment was a reclassification within stockholders&#8217; equity from additional paid-in capital to noncontrolling interest in Akcea equal to the amount of stock-based compensation expense Akcea had recognized. Additionally, w</span>e reflected changes in our ownership percentage in our financial statements as an adjustment to noncontrolling interest in the period the change occurred.</div>
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<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ConcentrationRiskCreditRisk', window );">Concentration of Credit Risk</a></td>
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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>

<div><br/></div>

<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>
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<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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 statement of operations. We use the specific identification method to determine the cost of securities sold.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We also have equity investments of less than 20 percent ownership in publicly and privately held biotechnology companies that we received as part of a technology license or partner agreement. At December 31, 2020, we held equity investments in two publicly held companies, ProQR Therapeutics N.V., or ProQR, and Antisense Therapeutics Limited, or ATL. We also held equity investments in seven privately-held companies, Aro Biotherapeutics, Atlantic Pharmaceuticals Limited, Dynacure SAS, Empirico, Inc., Flamingo Therapeutics BV, Seventh Sense Biosystems and Suzhou-Ribo Life Science Co, Ltd.</div>

<div><br/></div>

<div 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 statement of operations. We account for our equity investments in privately held companies at their cost minus impairments, plus or minus changes resulting from observable price changes in orderly transactions for the identical or similar investment of the same issuer. For example, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">during the second and fourth quarters of 2020, we revalued our investments in </span>three<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> privately held companies, Dynacure, Suzhou-Ribo and Aro Biotherapeutics because the companies sold additional equity securities that were similar to the equity we own. These observable price changes resulted in us recognizing a $</span>6.3<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million gain on our investment in Dynacure, a $</span>3.0<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million gain on our investment in Suzhou-Ribo and a $</span>5.5<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million gain on our investment in Aro Biotherapeutics in our consolidated statement of operations during 2020 because the sales were at higher prices compared to our recorded value.</span></div>
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<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_InventoryPolicyTextBlock', window );">Inventory Valuation</a></td>
<td class="text">
<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Inventory Valuation</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 on our consolidated balance sheet 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.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We obtained the first regulatory approval for TEGSEDI in July 2018 and for WAYLIVRA in May 2019. At December 31, 2020, our physical inventory for TEGSEDI and WAYLIVRA included API that we produced prior to when we obtained regulatory approval. As such, this API has no cost basis as we had previously expensed the costs as R&amp;D expenses.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We 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. We recorded an <span style="-sec-ix-hidden:Fact_b86d72920caa47448f2abd7be8e5c180"><span style="-sec-ix-hidden:Fact_1261d93c836d4d94bba4bd8c45f1e569">insignificant</span></span> amount of inventory write-offs during the years ended December 31, 2020 and 2019. We did not record any inventory write-offs for the year ended December 31, 2018.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our inventory consisted of the following (in thousands):</div>

<div><br/></div>

<table cellpadding="0" cellspacing="0" id="z420cf186c4154a629acd33b8e4e537ba" 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"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/></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;">2020</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;">2019</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Raw materials:</div></td>
    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: justify; text-indent: -9pt; margin-left: 19.4pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Raw materials- clinical</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">9,206</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">9,363</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;">7,502</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;">6,520</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;">16,708</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;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">15,883</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 76%;" valign="bottom"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Work in process</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2,252</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;">2,039</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;">3,005</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;">258</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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">21,965</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">18,180</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="top.Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentPolicyTextBlock', window );">Property, Plant and Equipment</a></td>
<td class="text">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Property, Plant and Equipment</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We carry our property, plant and equipment at cost and depreciate it on the straight-line method over its estimated useful life, which consists of the following (in thousands):</div>

<div><br/></div>

<table cellpadding="0" cellspacing="0" id="z0d198c5954a847b59f5bfeab5aaeb505" 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"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/></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 Useful Lives</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">December 31,</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(in years)</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2020</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;">2019</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Computer software, laboratory, manufacturing and other equipment</div></td>
    <td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3 to 10</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">68,990</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">60,965</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom;" valign="bottom"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Building, building improvements and building systems</div></td>
    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">15 to 40</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">137,879</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;">119,830</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Land improvements</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">20</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
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  <tr>
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    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>
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  </tr>
  <tr>
    <td style="vertical-align: bottom; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Furniture and fixtures</div></td>
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    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
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  <tr>
    <td style="vertical-align: bottom; width: 64%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
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    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
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  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Less accumulated depreciation</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
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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;">(74,013</div></td>
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  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 64%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">158,015</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;">130,589</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Land</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">23,062</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">23,062</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 64%; padding-bottom: 4px;" valign="bottom"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#160;Total</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">181,077</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">153,651</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
</table>

<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We depreciate our leasehold improvements using the shorter of the estimated useful life or remaining lease term.</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="top.Show.showAR( this, 'defref_us-gaap_FairValueOfFinancialInstrumentsPolicy', window );">Fair Value of Financial Instruments</a></td>
<td class="text">
<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Fair Value of Financial Instruments</div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> </span><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We have estimated the fair value of our financial instruments. The amounts reported for cash, accounts receivable, accounts payable and accrued expenses approximate the fair value because of their short maturities. We report our investment securities at their estimated fair value based on quoted market prices for identical or similar instruments.</div>
<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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 on our consolidated balance sheet 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 concluded we were reasonably certain that we will 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 current leases do not provide an interest rate implicit in the lease, we used our incremental borrowing rate, based on the information available on the date we adopted Topic 842 (January 2019), 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. We recognize period expenses, such as common area maintenance expenses, in the period we incur the expense.</div>
<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ImpairmentOrDisposalOfLongLivedAssetsIncludingIntangibleAssetsPolicyPolicyTextBlock', window );">Long-Lived Assets</a></td>
<td class="text">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Long-Lived Assets</div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> </span><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We evaluate long-lived assets, which include property, plant and equipment and patent costs, 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. We recorded charges of $1.9 million, $2.2 million and $0.8 million for the years ended December 31, 2020, 2019 and 2018, respectively, related to the write-down of patents.</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="top.Show.showAR( this, 'defref_us-gaap_UseOfEstimates', window );">Use of Estimates</a></td>
<td class="text">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Use of Estimates</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The preparation of consolidated financial statements in conformity with accounting principles generally accepted in the U.S. requires management to make estimates and assumptions that affect the amounts reported in the consolidated financial statements and accompanying notes. Actual results could differ from those estimates.</div>
<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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, 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 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. We estimate the expected term of options granted based on 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;">We recognize compensation expense for option awards and RSUs 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;">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 vest annually over a four-year period. RSUs granted after June 2020 to our board of directors vest annually.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">See Note 4, <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="top.Show.showAR( this, 'defref_us-gaap_StockholdersEquityPolicyTextBlock', window );">Accumulated Other Comprehensive Loss</a></td>
<td class="text">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Accumulated Other Comprehensive Loss</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Accumulated other comprehensive loss is comprised of unrealized gains and losses on investments, net of taxes and currency translation adjustments. The following table summarizes changes in accumulated other comprehensive loss for the years ended December 31, </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">2020</span><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;">2019</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> and </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">2018</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> (in thousands):</span></div>

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

<table cellpadding="0" cellspacing="0" id="z0f84e575a1a8436991d62963b2899dd6" 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"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/></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;">2020</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;">2019</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;">2018</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Beginning balance accumulated other comprehensive loss</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(25,290</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(32,016</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;">(31,759</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 64%;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Unrealized gains (losses) on securities, net of tax (1)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3,729</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6,633</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;">(280</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: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Currency translation adjustment</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">617</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">93</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-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>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 64%; padding-bottom: 2px;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Adjustments to other comprehensive loss from purchase of noncontrolling interest of Akcea Therapeutics, Inc.</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(127</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <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: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net other comprehensive loss for the period</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4,219</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; 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;">6,726</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;">(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"><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: 4px;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Ending balance accumulated other comprehensive loss</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(21,071</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(25,290</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(32,016</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
</table>

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

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z9ecfa3f5cf504526a0786f25593849bf" 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; 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; text-indent: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We did not have tax expense included in our other comprehensive loss for the year ended December 31, 2020. For the years ended December 31, 2019 and 2018, we had a tax benefit $1.4 million and $0.3 million included in other comprehensive loss respectively.&#160;</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="top.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;">At issuance, we accounted for our convertible debt instruments, including our 0.125 percent senior convertible notes, or 0.125% Notes, and 1 percent senior convertible notes, or 1% Notes, that may be settled in cash upon conversion (including partial cash settlement) by separating the liability and equity components of the instruments in a manner that reflects our nonconvertible debt borrowing rate on the date the notes were issued. In reviewing debt issuances, we were not able to identify any comparable companies that issued non-convertible debt instruments at the time of the issuance of the convertible notes. Therefore, we estimated the fair value of the liability component of our notes by using assumptions that market participants would use in pricing a debt instrument, including market interest rates, credit standing, yield curves and volatilities.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We assigned a value to the debt component of our convertible notes equal to the estimated fair value of similar debt instruments without the conversion feature, which resulted in us recording our debt at a discount. We are amortizing our debt issuance costs and debt discount over the life of the convertible notes as additional non-cash interest expense utilizing the effective interest method. For additional information, see Note 3, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Long-Term Obligations and Commitments</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 1% Notes mature in November 2021. Therefore, as of December 31, 2020, we classified the liability component of the 1% Notes as a current liability on our consolidated balance sheet.</div>

<div><br/></div>

<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 2020, the FASB issued guidance simplifying the accounting for convertible debt instruments. See the section titled &#8220;Impact of Recently Issued Accounting Standards&#8221; below for details.</div>
<span></span>
</td>
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<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_DerivativesPolicyTextBlock', window );">Call Spread</a></td>
<td class="text">
<div style="text-align: left; 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 0.125% Notes, we entered into a call spread transaction, which was 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 Derivatives and Hedging &#8211; Contracts in Entity&#8217;s Own Equity 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 sheet. 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>
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<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_SegmentReportingPolicyPolicyTextBlock', window );">Segment Information</a></td>
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<div style="text-align: justify; 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;">Through 2020, we had two operating segments, our Ionis Core segment and Akcea Therapeutics. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Akcea was focused on developing and commercializing medicines to treat patients with serious and rare diseases. We have provided segment financial information and results for our Ionis Core segment and our Akcea Therapeutics segment based on the segregation of revenues and expenses that our chief decision maker reviewed to assess operating performance and to make operating decisions through 2020. We allocated a portion of Ionis&#8217; development, R&amp;D support and general and administrative expenses to Akcea for work Ionis performed on behalf of Akcea and we billed Akcea for these expenses.</span></div>
<span></span>
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<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_FairValueMeasurementPolicyPolicyTextBlock', 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 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 held 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 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, 2020 and 2019&#160;<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">that we regularly measure and carry at fair value</span>. At December 31, 2019, our ProQR investment was <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">subject to trading restrictions until the fourth quarter of 2020, as a result we</span> included a lack of marketability discount in valuing this investment, which is a Level 3 input. As of December 31, 2020, our ProQR investment was no longer subject to trading restrictions. As of December 31, 2020, we did not have any investments which we valued using Level 3 inputs. The following tables segregate each security type by the level within the fair value hierarchy of the valuation techniques we utilized to determine the respective securities&#8217; fair value (in thousands):</div>

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    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">At</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">December 31, 2020</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;">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;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
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  <tr>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
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    <td colspan="1" style="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"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
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  <tr>
    <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>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">846,315</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 (4)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">174,861</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">&#160;</td>
    <td colspan="1" style="vertical-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>
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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: 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;">358,497</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;">358,497</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 (4)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">136,309</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-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;">136,309</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 (4)</div></div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6,225</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6,225</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;">Investment in ProQR Therapeutics N.V. (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;">2,031</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;">2,031</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;">1,745,363</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>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>
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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>
  </tr>
</table>

<div><br/></div>

<table cellpadding="0" cellspacing="0" id="z42641d00b2bd400e81caba6eddf342f0" 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;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">At</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">December 31, 2019</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;">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;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Significant Other</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Observable Inputs</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(Level 2)</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Significant</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Unobservable Inputs</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(Level 3)</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
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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;">418,406</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">418,406</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-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>
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  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%;" valign="bottom"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Corporate debt securities (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">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,102,568</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;">1,102,568</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by U.S. government agencies (7)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">329,404</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-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;">329,404</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%;" valign="bottom"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by the U.S. Treasury (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;">363,694</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;">363,694</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by states of the U.S. and political subdivisions of the states (4)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">40,407</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-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;">40,407</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px;" valign="bottom"><div><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Investment in ProQR Therapeutics N.V. (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;">4,506</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>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4,506</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: 52%; 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;">2,258,985</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">&#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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">782,100</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">1,472,379</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;">4,506</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" id="z791574a09f2444c599172d57b45fe997" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
  <tr>
    <td style="width: 36pt; vertical-align: top; align: right; 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 on our consolidated balance sheet.</div></td>
  </tr>
</table>

<div><br/></div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="za3c5f136d4254206a5ec01a41ea4efb9" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
  <tr>
    <td style="width: 36pt; vertical-align: top; align: right; 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;">$10.0 million included in cash and cash equivalents on our consolidated balance sheet, with the difference included in short-term investments on our consolidated balance sheet.</div></td>
  </tr>
</table>

<div><br/></div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z148638abbe4544afb1bfb13a3a3df99e" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
  <tr>
    <td style="width: 36pt; vertical-align: top; align: right; 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;">$17.5 million included in cash and cash equivalents on our consolidated balance sheet, with the difference included in short-term investments on our consolidated balance sheet.</div></td>
  </tr>
</table>

<div><br/></div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="zfe5f26749b614dbcb042f4c2f2ba5a12" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
  <tr>
    <td style="width: 36pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(4)</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Included in short-term investments.</div></td>
  </tr>
</table>

<div><br/></div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z7c2aa671a6d84170836be6a95eff7f0e" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
  <tr>
    <td style="width: 36pt; vertical-align: top; align: right; 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 on our consolidated balance sheet.</div></td>
  </tr>
</table>

<div><br/></div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="zae152b0de27346b784a63d2fad55dc16" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
  <tr>
    <td style="width: 36pt; vertical-align: top; align: right; 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;">$19.0 million included in cash and cash equivalents on our consolidated balance sheet, with the difference included in short-term investments on our consolidated balance sheet.</div></td>
  </tr>
</table>

<div><br/></div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z13ffd34009fd4d8ea5be9d956bd94c78" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
  <tr>
    <td style="width: 36pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(7)</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$0.8 million included in cash and cash equivalents on our consolidated balance sheet, with the difference included in short-term investments on our consolidated balance sheet.&#160; </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="top.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, no assurance can be given that the final tax outcome of these matters will not be different from that which is 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 such determination is made.</div>

<div><br/></div>

<div 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.<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> 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.</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 do not provide for a U.S. income tax liability and foreign withholding taxes on undistributed foreign earnings of our foreign subsidiaries.</div>
<span></span>
</td>
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<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_NewAccountingPronouncementsPolicyPolicyTextBlock', window );">Impact of 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;">Impact of 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 June 2016, the FASB issued guidance that changes the measurement of credit losses for most financial assets and certain other instruments. If we have credit losses, this updated guidance requires us to record allowances for these instruments under a new expected credit loss model. This model requires us to estimate the expected credit loss of an instrument over its lifetime, which represents the portion of the amortized cost basis we do not expect to collect. The new guidance requires us to remeasure our allowance in each reporting period we have credit losses. We adopted this new guidance on January 1, 2020. This guidance did not have an impact on our consolidated financial statements.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In August 2018, the FASB issued clarifying guidance on how to account for implementation costs related to cloud-servicing arrangements. The guidance states that if these fees qualify to be capitalized and amortized over the service period, they need to be expensed in the same line item as the service expense and recognized in the same balance sheet category. The update can be applied either retrospectively or prospectively to all implementation costs incurred after the date of adoption. We adopted this guidance on January 1, 2020 on a prospective basis. This guidance did not have an impact on our consolidated financial statements.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In November 2018, the FASB issued clarifying guidance of the interaction between the collaboration accounting guidance and the new revenue recognition guidance we adopted on January 1, 2018 (Topic 606). Below is the clarifying guidance and how we implemented it (in italics):</div>

<div><br/></div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="zf1701d3f1d8d4160978d38fc5e5b4c66" 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; align: right; 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;">When a participant is considered a customer in a collaborative arrangement, all of the associated accounting under Topic 606 should be applied.</div></td>
  </tr>
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<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z3d884347466d4766902ab98141f40262" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
  <tr>
    <td style="width: 72pt;"/>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">&#9679;</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;">We are applying all of the associated accounting under Topic 606 when we determine a participant in a collaborative arrangement is a customer.</div></td>
  </tr>
</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="zbefb18546da74bf487f114918d77add3" 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; align: right; 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;">Adds &#8220;unit of account&#8221; concept to collaboration accounting guidance to align with Topic 606. The &#8220;unit of account&#8221; concept is used to determine if revenue is recognized or if a contra expense is recognized from consideration received under a collaboration.</div></td>
  </tr>
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<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z28c82932c2e1414281433d5974927174" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
  <tr>
    <td style="width: 72pt;"/>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">&#9679;</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;">We use the &#8220;unit of account&#8221; concept when we receive consideration under a collaborative arrangement to determine when we recognize revenue or a contra expense.</div></td>
  </tr>
</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="za50af4149c204796bc74ae610430cd43" 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; align: right; 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;">The clarifying guidance precludes us from recognizing revenue under Topic 606 when we determine a transaction with a collaborative partner is not a customer and is not directly related to the sales to third parties.</div></td>
  </tr>
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<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="zd9d21a16a5b3482c85eb10cf58a06d3e" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
  <tr>
    <td style="width: 72pt;"/>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">&#9679;</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;">When we conclude a collaboration partner is not a customer and is not directly related to the sales to third parties, we do not recognize revenue for the transaction.</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 adopted this new guidance on January 1, 2020. This guidance did not have any impact on our consolidated financial statements.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In August 2020, the FASB issued guidance </span>which simplifies the accounting for convertible instruments<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, amends the guidance on derivative scope exceptions for contracts in an entity&#8217;s own equity, and modifies the guidance on diluted earnings per share calculations as a result of these changes. Under our current outstanding convertible debt arrangements, we anticipate the following impacts:</span></div>

<div><br/></div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="zcbb885b9cab547a1b31cd283712248a2" 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: 36pt; vertical-align: top; align: right; 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;">We will no longer separate our existing convertible debt into liability and equity components. Therefore, we will no longer recognize a debt discount for the value of the conversion option, instead we will record the face value of the convertible debt as a liability on our consolidated balance sheet;</div></td>
  </tr>
</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z66fb90d1a5be4351bc55d49e62d382d6" 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; align: right; 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;">We will record cash interest expense plus amortization of debt issuance costs to interest expense. Since we will not recognize a debt discount, we will no longer record the amortization of a debt discount to interest expense; and</div></td>
  </tr>
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<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="ze1e1f5e6552b4bfc822ec7f94c42c685" 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; align: right; 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;">We do not expect our EPS calculation to not change under this update. We plan to continue to use the if-converted method to calculate diluted earnings per share.</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 plan to adopt this guidance in the first quarter of 2021 under the full retrospective approach, meaning we will apply the guidance to all periods presented beginning in the first quarter of 2021.</div>
<span></span>
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<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Disclosure of accounting policy for credit risk.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 275<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (d)<br> -URI http://asc.fasb.org/extlink&amp;oid=99393423&amp;loc=d3e5967-108592<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 942<br> -SubTopic 825<br> -Section 50<br> -Paragraph 1<br> -URI http://asc.fasb.org/extlink&amp;oid=108315417&amp;loc=d3e61044-112788<br></p></div>
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<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">- Definition</a><div><p>Disclosure of accounting policy for subsidiaries or other investments that are consolidated, including the accounting treatment for intercompany accounts or transactions and any noncontrolling interest.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 810<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -URI http://asc.fasb.org/extlink&amp;oid=109239629&amp;loc=d3e5614-111684<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 235<br> -SubTopic 10<br> -Section 50<br> -Paragraph 3<br> -URI http://asc.fasb.org/extlink&amp;oid=84158767&amp;loc=d3e18780-107790<br></p></div>
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<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 705<br> -URI http://asc.fasb.org/topic&amp;trid=2122478<br></p></div>
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<a href="javascript:void(0);" onclick="top.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>
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<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 815<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -URI http://asc.fasb.org/extlink&amp;oid=121590274&amp;loc=d3e41620-113959<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 235<br> -SubTopic 10<br> -Section 50<br> -Paragraph 3<br> -URI http://asc.fasb.org/extlink&amp;oid=84158767&amp;loc=d3e18780-107790<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 815<br> -SubTopic 10<br> -Section 50<br> -Paragraph 4<br> -URI http://asc.fasb.org/extlink&amp;oid=121590274&amp;loc=d3e41638-113959<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 815<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1A<br> -URI http://asc.fasb.org/extlink&amp;oid=121590274&amp;loc=SL5579245-113959<br><br>Reference 5: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 815<br> -SubTopic 10<br> -Section 50<br> -Paragraph 7<br> -URI http://asc.fasb.org/extlink&amp;oid=121590274&amp;loc=d3e41675-113959<br><br>Reference 6: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 235<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.4-08.(n))<br> -URI http://asc.fasb.org/extlink&amp;oid=120395691&amp;loc=d3e23780-122690<br><br>Reference 7: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 815<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -URI http://asc.fasb.org/extlink&amp;oid=121590274&amp;loc=SL5579240-113959<br></p></div>
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">- Definition</a><div><p>Disclosure of accounting policy for computing basic and diluted earnings or loss per share for each class of common stock and participating security. Addresses all significant policy factors, including any antidilutive items that have been excluded from the computation and takes into account stock dividends, splits and reverse splits that occur after the balance sheet date of the latest reporting period but before the issuance of the financial statements.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (c)<br> -URI http://asc.fasb.org/extlink&amp;oid=6371337&amp;loc=d3e3550-109257<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 235<br> -SubTopic 10<br> -Section 50<br> -Paragraph 3<br> -URI http://asc.fasb.org/extlink&amp;oid=84158767&amp;loc=d3e18780-107790<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -URI http://asc.fasb.org/extlink&amp;oid=6371337&amp;loc=d3e3630-109257<br></p></div>
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">- Definition</a><div><p>Disclosure of accounting policy for fair value measurements of financial and non-financial assets, liabilities and instruments classified in shareholders' equity. Disclosures include, but are not limited to, how an entity that manages a group of financial assets and liabilities on the basis of its net exposure measures the fair value of those assets and liabilities.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">- Definition</a><div><p>Disclosure of accounting policy for determining the fair value of financial instruments.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 820<br> -SubTopic 10<br> -Section 60<br> -Paragraph 1<br> -URI http://asc.fasb.org/extlink&amp;oid=7493716&amp;loc=d3e21868-110260<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 825<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -URI http://asc.fasb.org/extlink&amp;oid=121572278&amp;loc=d3e13279-108611<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 235<br> -SubTopic 10<br> -Section 50<br> -Paragraph 3<br> -URI http://asc.fasb.org/extlink&amp;oid=84158767&amp;loc=d3e18780-107790<br></p></div>
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">- Definition</a><div><p>Disclosure of accounting policy for the impairment and disposal of long-lived assets including goodwill and other intangible assets.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.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="top.Show.hideAR();">X</a></td></tr>
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<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 45<br> -Paragraph 25<br> -URI http://asc.fasb.org/extlink&amp;oid=120406818&amp;loc=d3e32247-109318<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 20<br> -URI http://asc.fasb.org/extlink&amp;oid=84230637&amp;loc=d3e32847-109319<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 954<br> -SubTopic 740<br> -Section 50<br> -Paragraph 1<br> -URI http://asc.fasb.org/extlink&amp;oid=6491622&amp;loc=d3e9504-115650<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 235<br> -SubTopic 10<br> -Section 50<br> -Paragraph 3<br> -URI http://asc.fasb.org/extlink&amp;oid=84158767&amp;loc=d3e18780-107790<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 19<br> -URI http://asc.fasb.org/extlink&amp;oid=84230637&amp;loc=d3e32840-109319<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -URI http://asc.fasb.org/extlink&amp;oid=116657188&amp;loc=SL116659661-227067<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 9<br> -URI http://asc.fasb.org/extlink&amp;oid=84230637&amp;loc=d3e32639-109319<br><br>Reference 8: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 45<br> -Paragraph 28<br> -URI http://asc.fasb.org/extlink&amp;oid=120406818&amp;loc=d3e32280-109318<br><br>Reference 9: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 17<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=84230637&amp;loc=d3e32809-109319<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_IncomeTaxPolicyTextBlock</td>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Disclosure of accounting policy for finite-lived intangible assets. This accounting policy also might address: (1) the amortization method used; (2) the useful lives of such assets; and (3) how the entity assesses and measures impairment of such assets.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 235<br> -SubTopic 10<br> -Section 50<br> -Paragraph 3<br> -URI http://asc.fasb.org/extlink&amp;oid=84158767&amp;loc=d3e18780-107790<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 926<br> -SubTopic 20<br> -Section 50<br> -Paragraph 5<br> -URI http://asc.fasb.org/extlink&amp;oid=120154696&amp;loc=d3e54445-107959<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 350<br> -SubTopic 30<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=66006027&amp;loc=d3e16323-109275<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 920<br> -SubTopic 350<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=120155617&amp;loc=SL120155638-234783<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 920<br> -SubTopic 350<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=120155617&amp;loc=SL120155628-234783<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 920<br> -SubTopic 350<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=120155617&amp;loc=SL120155628-234783<br></p></div>
<a href="javascript:void(0);" onclick="top.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="top.Show.hideAR();">X</a></td></tr>
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<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 330<br> -SubTopic 10<br> -Section 50<br> -Paragraph 4<br> -URI http://asc.fasb.org/extlink&amp;oid=116847112&amp;loc=d3e4556-108314<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 235<br> -SubTopic 10<br> -Section 50<br> -Paragraph 3<br> -URI http://asc.fasb.org/extlink&amp;oid=84158767&amp;loc=d3e18780-107790<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -URI http://asc.fasb.org/extlink&amp;oid=6361739&amp;loc=d3e7789-107766<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 330<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -URI http://asc.fasb.org/extlink&amp;oid=116847112&amp;loc=d3e4492-108314<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 270<br> -SubTopic 10<br> -Section 45<br> -Paragraph 6<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=116846552&amp;loc=d3e543-108305<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 330<br> -URI http://asc.fasb.org/topic&amp;trid=2126998<br><br>Reference 7: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02.6(b))<br> -URI http://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_InvestmentPolicyTextBlock">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Disclosure of accounting policy for investment in financial asset.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 944<br> -SubTopic 220<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-04(3)(b))<br> -URI http://asc.fasb.org/extlink&amp;oid=120400993&amp;loc=SL114874131-224263<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 323<br> -SubTopic 10<br> -Section 50<br> -Paragraph 3<br> -Subparagraph (a)(2)<br> -URI http://asc.fasb.org/extlink&amp;oid=114001798&amp;loc=d3e33918-111571<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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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<tr>
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<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_LesseeLeasesPolicyTextBlock">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 842<br> -SubTopic 20<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=121609121&amp;loc=SL77918666-209980<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>
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</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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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><strong> Data Type:</strong></td>
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<td><strong> Period Type:</strong></td>
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</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_OrganizationConsolidationAndPresentationOfFinancialStatementsAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>
</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>
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<tr>
<td><strong> Period Type:</strong></td>
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</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_PropertyPlantAndEquipmentPolicyTextBlock">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 958<br> -SubTopic 360<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (d)<br> -URI http://asc.fasb.org/extlink&amp;oid=120429125&amp;loc=d3e99779-112916<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02.13(a))<br> -URI http://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 958<br> -SubTopic 360<br> -Section 50<br> -Paragraph 6<br> -URI http://asc.fasb.org/extlink&amp;oid=120429125&amp;loc=d3e99893-112916<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 360<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -URI http://asc.fasb.org/extlink&amp;oid=6391035&amp;loc=d3e2868-110229<br><br>Reference 5: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 235<br> -SubTopic 10<br> -Section 50<br> -Paragraph 3<br> -URI http://asc.fasb.org/extlink&amp;oid=84158767&amp;loc=d3e18780-107790<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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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<tr>
<td><strong> Data Type:</strong></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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</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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 235<br> -SubTopic 10<br> -Section 50<br> -Paragraph 3<br> -URI http://asc.fasb.org/extlink&amp;oid=84158767&amp;loc=d3e18780-107790<br><br>Reference 2: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 310<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -URI http://asc.fasb.org/extlink&amp;oid=121611835&amp;loc=d3e5033-111524<br><br>Reference 3: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 310<br> -SubTopic 20<br> -Section 50<br> -Paragraph 4<br> -URI http://asc.fasb.org/extlink&amp;oid=84159169&amp;loc=d3e10178-111534<br><br>Reference 4: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 310<br> -SubTopic 20<br> -Section 50<br> -Paragraph 2<br> -URI http://asc.fasb.org/extlink&amp;oid=84159169&amp;loc=d3e10149-111534<br><br>Reference 5: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 310<br> -SubTopic 20<br> -Section 50<br> -Paragraph 1<br> -URI http://asc.fasb.org/extlink&amp;oid=84159169&amp;loc=d3e10133-111534<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ReceivablesPolicyTextBlock</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<tr>
<td><strong> Data Type:</strong></td>
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</tr>
<tr>
<td><strong> Balance Type:</strong></td>
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<tr>
<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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 235<br> -SubTopic 10<br> -Section 50<br> -Paragraph 3<br> -URI http://asc.fasb.org/extlink&amp;oid=84158767&amp;loc=d3e18780-107790<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 730<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -URI http://asc.fasb.org/extlink&amp;oid=6420194&amp;loc=d3e21568-108373<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ResearchAndDevelopmentExpensePolicy</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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</tr>
<tr>
<td><strong> Data Type:</strong></td>
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</tr>
<tr>
<td><strong> Balance Type:</strong></td>
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</tr>
<tr>
<td><strong> Period Type:</strong></td>
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</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_RevenueFromContractWithCustomerPolicyTextBlock">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Disclosure of accounting policy for revenue from contract with customer.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 50<br> -Paragraph 17<br> -URI http://asc.fasb.org/extlink&amp;oid=121604090&amp;loc=SL49130561-203045<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 50<br> -Paragraph 20<br> -Subparagraph (d)<br> -URI http://asc.fasb.org/extlink&amp;oid=121604090&amp;loc=SL49130566-203045<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 50<br> -Paragraph 18<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=121604090&amp;loc=SL49130563-203045<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -URI http://asc.fasb.org/topic&amp;trid=49130388<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 50<br> -Paragraph 20<br> -Subparagraph (c)<br> -URI http://asc.fasb.org/extlink&amp;oid=121604090&amp;loc=SL49130566-203045<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 50<br> -Paragraph 18<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=121604090&amp;loc=SL49130563-203045<br><br>Reference 7: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 235<br> -SubTopic 10<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (e)<br> -URI http://asc.fasb.org/extlink&amp;oid=84158767&amp;loc=d3e18823-107790<br><br>Reference 8: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 50<br> -Paragraph 20<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=121604090&amp;loc=SL49130566-203045<br><br>Reference 9: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 50<br> -Paragraph 19<br> -URI http://asc.fasb.org/extlink&amp;oid=121604090&amp;loc=SL49130564-203045<br><br>Reference 10: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 50<br> -Paragraph 20<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=121604090&amp;loc=SL49130566-203045<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_RevenueFromContractWithCustomerPolicyTextBlock</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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</tr>
<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>
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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_RevenueRecognitionPolicyTextBlock">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Disclosure of accounting policy for revenue. Includes revenue from contract with customer and from other sources.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 235<br> -SubTopic 10<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (e)<br> -URI http://asc.fasb.org/extlink&amp;oid=84158767&amp;loc=d3e18823-107790<br><br>Reference 2: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 235<br> -SubTopic 10<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (f)<br> -URI http://asc.fasb.org/extlink&amp;oid=84158767&amp;loc=d3e18823-107790<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_RevenueRecognitionPolicyTextBlock</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>nonnum:textBlockItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_SegmentReportingPolicyPolicyTextBlock">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Disclosure of accounting policy for segment reporting.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 29<br> -Subparagraph (e)<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e8864-108599<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 235<br> -SubTopic 10<br> -Section 50<br> -Paragraph 3<br> -URI http://asc.fasb.org/extlink&amp;oid=84158767&amp;loc=d3e18780-107790<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 29<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e8864-108599<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 41<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e9038-108599<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 29<br> -Subparagraph (c)<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e8864-108599<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 29<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e8864-108599<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 29<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e8864-108599<br><br>Reference 8: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 29<br> -Subparagraph (d)<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e8864-108599<br></p></div>
<a href="javascript:void(0);" onclick="top.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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 235<br> -SubTopic 10<br> -Section 50<br> -Paragraph 3<br> -URI http://asc.fasb.org/extlink&amp;oid=84158767&amp;loc=d3e18780-107790<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (b),(f)<br> -URI http://asc.fasb.org/extlink&amp;oid=120381028&amp;loc=d3e5070-113901<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -URI http://asc.fasb.org/extlink&amp;oid=120381028&amp;loc=d3e5047-113901<br></p></div>
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<tr>
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<td style="white-space:nowrap;">us-gaap_ShareBasedCompensationOptionAndIncentivePlansPolicy</td>
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<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Disclosure of accounting policy for its capital stock transactions, including dividends and accumulated other comprehensive income.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 505<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -URI http://asc.fasb.org/extlink&amp;oid=109259400&amp;loc=d3e21459-112644<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 235<br> -SubTopic 10<br> -Section 50<br> -Paragraph 3<br> -URI http://asc.fasb.org/extlink&amp;oid=84158767&amp;loc=d3e18780-107790<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 235<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -URI http://asc.fasb.org/extlink&amp;oid=84158767&amp;loc=d3e18726-107790<br></p></div>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 310<br> -URI http://asc.fasb.org/topic&amp;trid=2196771<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_TradeAndOtherAccountsReceivableUnbilledReceivablesPolicy</td>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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;">v3.20.4</span><table class="report" border="0" cellspacing="2" id="idm140142735389560">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Organization and Significant Accounting Policies (Tables)<br></strong></div></th>
<th class="th" colspan="1">12 Months Ended</th>
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<tr><th class="th"><div>Dec. 31, 2020</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;">Our basic net income (loss) per share was calculated as follows (in thousands, except per share amounts):</div>

<div><br/></div>

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    <td style="vertical-align: bottom; border-bottom: #000000 2px solid; white-space: nowrap;" valign="bottom"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Year Ended December 31, 2020</div></td>
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    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Akcea</span>&#8217;<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">s</span></div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Net Loss</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Per Share</div></td>
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    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Basic Net Loss</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Per Share</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Calculation</div></td>
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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;">$</div></td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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    <td style="vertical-align: top; width: 64%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Akcea&#8217;s net loss in the post-acquisition period attributable to our ownership</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
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  <tr>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
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  </tr>
  <tr>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net loss available to Ionis common stockholders</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(451,487</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Weighted average shares outstanding</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">139,612</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Basic net loss per share</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(3.23</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><br/></div>

<table cellpadding="0" cellspacing="0" id="z7190f4cfc9904c35afaf55ca55271bf2" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td style="vertical-align: bottom; border-bottom: #000000 2px solid; white-space: nowrap;" valign="bottom"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Year Ended December 31, 2019</div></td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Weighted</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Average Shares</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Owned in Akcea</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Akcea</span>&#8217;<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">s</span></div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Net Income</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Per Share</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Basic Net Income</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Per Share</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Calculation</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Common shares</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;">70,100</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; 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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.49</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">34,073</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: 64%; white-space: nowrap;" valign="bottom"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Akcea&#8217;s net income attributable to our ownership</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">&#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%; 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">&#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%; white-space: nowrap;" 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: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Ionis&#8217; stand-alone net income</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">262,490</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>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net income available to Ionis common stockholders</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
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  <tr>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; 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; text-align: right; width: 9%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
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</table>

<div><br/></div>

<table cellpadding="0" cellspacing="0" id="zc4df006abbbb4d5b9a0a303fb389d2b3" 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="text-align: 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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    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Basic Net Income</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Per Share</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Calculation</div></td>
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  </tr>
  <tr>
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    <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>
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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"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(2.74</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">(163,938</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; white-space: nowrap;" valign="bottom"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Akcea&#8217;s net loss attributable to our ownership</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">&#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%; 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">&#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%; white-space: nowrap;" valign="bottom">&#160;</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; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(163,938</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: 64%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Ionis&#8217; stand-alone net income</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">440,806</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: top; width: 64%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net income available to Ionis common stockholders</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times 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; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">276,868</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Weighted average shares outstanding</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">132,320</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: top; width: 64%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Basic net income per share</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2.09</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="top.Show.showAR( this, 'defref_us-gaap_ScheduleOfEarningsPerShareBasicAndDilutedTableTextBlock', window );">Basic and Diluted Net Income Per Share</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;">For the years ended December 31, 2019 and 2018, we had net income available to Ionis common stockholders. As a result, we computed diluted net income per share using the weighted-average number of common shares and dilutive common equivalent shares outstanding during each period.</span> We calculated our diluted net income per share as follows <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(in thousands except per share amounts):</span></div>

<div><br/></div>

<table cellpadding="0" cellspacing="0" id="zbebb8966d0bf411b9c7f046d05640cb2" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
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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">&#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>
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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%;" 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="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>
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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="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>
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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%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
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  <tr>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>
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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">&#160;</td>
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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>
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<div><br/></div>

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    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
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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%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
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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>
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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">&#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>
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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>
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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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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; 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>
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    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">514</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Shares issuable related to our ESPP</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; 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;">6</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%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; padding-bottom: 4px;" 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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">276,868</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">134,056</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">2.07</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="top.Show.showAR( this, 'defref_us-gaap_ScheduleofFiniteLivedIntangibleAssetsFutureAmortizationExpenseTableTextBlock', window );">Amortization Expense for Patents</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;">Based on our existing patents, we estimate amortization expense related to patents in each of the next five years to be the following:</div>

<div><br/></div>

<table cellpadding="0" cellspacing="0" id="z1566f0aad503425294fc597dc5e10f73" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td style="vertical-align: bottom; border-bottom: #000000 2px solid;" valign="bottom"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Year Ending December 31,</div></td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Amortization</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(in millions)</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;">2021</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2.1</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 88%;" valign="bottom"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2022</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">2.0</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; 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;">2023</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1.9</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 88%;" valign="bottom"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2024</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">1.7</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: 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;">2025</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1.6</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
</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="top.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" id="zc442150657ce4320af53f69853dbac04" 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"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/></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;">2020</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;">2019</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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">39,477</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">24,461</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;">8,264</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10,289</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;">11,559</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6,020</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;">30,861</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;">25,999</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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">90,161</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">66,769</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="top.Show.showAR( this, 'defref_us-gaap_ScheduleOfInventoryCurrentTableTextBlock', window );">Inventory</a></td>
<td class="text">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our inventory consisted of the following (in thousands):</div>

<div><br/></div>

<table cellpadding="0" cellspacing="0" id="z420cf186c4154a629acd33b8e4e537ba" 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"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/></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;">2020</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;">2019</div></td>
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    <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>
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  <tr>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
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  </tr>
  <tr>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>
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    <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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  </tr>
  <tr>
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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;">16,708</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;" 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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  </tr>
  <tr>
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    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
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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"><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;">3,005</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;">258</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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">21,965</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">18,180</div></td>
    <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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<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentTextBlock', window );">Property, Plant and Equipment</a></td>
<td class="text">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We carry our property, plant and equipment at cost and depreciate it on the straight-line method over its estimated useful life, which consists of the following (in thousands):</div>

<div><br/></div>

<table cellpadding="0" cellspacing="0" id="z0d198c5954a847b59f5bfeab5aaeb505" 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"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/></td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
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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;">(in years)</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2020</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;">2019</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Computer software, laboratory, manufacturing and other equipment</div></td>
    <td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3 to 10</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">68,990</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">60,965</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom;" valign="bottom"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Building, building improvements and building systems</div></td>
    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">15 to 40</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">137,879</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;">119,830</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Land improvements</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">20</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">8,391</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2,853</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom;" valign="bottom"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Leasehold improvements</div></td>
    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">5 to 15</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">17,263</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;">13,600</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Furniture and fixtures</div></td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">5 to 10</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">12,871</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">7,354</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 64%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
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  <tr>
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  <tr>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>
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<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ScheduleOfAccumulatedOtherComprehensiveIncomeLossTableTextBlock', window );">Changes in Accumulated Other Comprehensive Loss</a></td>
<td class="text">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Accumulated other comprehensive loss is comprised of unrealized gains and losses on investments, net of taxes and currency translation adjustments. The following table summarizes changes in accumulated other comprehensive loss for the years ended December 31, </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">2020</span><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;">2019</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> and </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">2018</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> (in thousands):</span></div>

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

<table cellpadding="0" cellspacing="0" id="z0f84e575a1a8436991d62963b2899dd6" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
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    <td colspan="10" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Year Ended December 31,</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
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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;">$</div></td>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 64%;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Unrealized gains (losses) on securities, net of tax (1)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
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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>
    <td colspan="1" style="vertical-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"><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: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Currency translation adjustment</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
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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>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #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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  </tr>
  <tr>
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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>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net other comprehensive loss for the period</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>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
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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;">(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"><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: 4px;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Ending balance accumulated other comprehensive loss</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>
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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"><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; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>
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  </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" id="z9ecfa3f5cf504526a0786f25593849bf" 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; 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; text-indent: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We did not have tax expense included in our other comprehensive loss for the year ended December 31, 2020. For the years ended December 31, 2019 and 2018, we had a tax benefit $1.4 million and $0.3 million included in other comprehensive loss respectively.&#160;</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="top.Show.showAR( this, 'defref_us-gaap_FairValueAssetsMeasuredOnRecurringBasisTextBlock', window );">Assets Measured at Fair Value on a Recurring Basis</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 tables present the major security types we held at December 31, 2020 and 2019&#160;<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">that we regularly measure and carry at fair value</span>. At December 31, 2019, our ProQR investment was <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">subject to trading restrictions until the fourth quarter of 2020, as a result we</span> included a lack of marketability discount in valuing this investment, which is a Level 3 input. As of December 31, 2020, our ProQR investment was no longer subject to trading restrictions. As of December 31, 2020, we did not have any investments which we valued using Level 3 inputs. The following tables segregate each security type by the level within the fair value hierarchy of the valuation techniques we utilized to determine the respective securities&#8217; fair value (in thousands):</div>

<div><br/></div>

<table cellpadding="0" cellspacing="0" id="z6070756b157447b980511cdf4857d355" 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"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 8pt;"/></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;">At</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">December 31, 2020</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;">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;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Significant Other</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Observable Inputs</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(Level 2)</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">221,125</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></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"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-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;">846,315</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;">846,315</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 (4)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">174,861</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">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">174,861</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </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;">358,497</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;">358,497</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 (4)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">136,309</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-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;">136,309</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 (4)</div></div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6,225</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6,225</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;">Investment in ProQR Therapeutics N.V. (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;">2,031</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;">2,031</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;">1,745,363</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>
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<div><br/></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; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
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  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%;" valign="bottom"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Corporate debt securities (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">&#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"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,102,568</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>
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  <tr>
    <td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by U.S. government agencies (7)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">329,404</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-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;">329,404</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
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  <tr>
    <td style="vertical-align: bottom; width: 52%;" valign="bottom"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by the U.S. Treasury (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;">363,694</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;">363,694</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by states of the U.S. and political subdivisions of the states (4)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">40,407</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-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;">40,407</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px;" valign="bottom"><div><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Investment in ProQR Therapeutics N.V. (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;">4,506</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>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4,506</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: 52%; 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;">$</div></td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">782,100</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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,472,379</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">4,506</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>

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  <tr>
    <td style="width: 36pt; vertical-align: top; align: right; 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 on our consolidated balance sheet.</div></td>
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<div><br/></div>

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    <td style="width: 36pt; vertical-align: top; align: right; 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;">$10.0 million included in cash and cash equivalents on our consolidated balance sheet, with the difference included in short-term investments on our consolidated balance sheet.</div></td>
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<div><br/></div>

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    <td style="width: 36pt; vertical-align: top; align: right; 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;">$17.5 million included in cash and cash equivalents on our consolidated balance sheet, with the difference included in short-term investments on our consolidated balance sheet.</div></td>
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<div><br/></div>

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  <tr>
    <td style="width: 36pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(4)</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Included in short-term investments.</div></td>
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    <td style="width: 36pt; vertical-align: top; align: right; 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 on our consolidated balance sheet.</div></td>
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<div><br/></div>

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    <td style="width: 36pt; vertical-align: top; align: right; 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;">$19.0 million included in cash and cash equivalents on our consolidated balance sheet, with the difference included in short-term investments on our consolidated balance sheet.</div></td>
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<div><br/></div>

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    <td style="width: 36pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(7)</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$0.8 million included in cash and cash equivalents on our consolidated balance sheet, with the difference included in short-term investments on our consolidated balance sheet.&#160; </div></td>
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<span style="display: none;">v3.20.4</span><table class="report" border="0" cellspacing="2" id="idm140142735706584">
<tr>
<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, 2020</div></th></tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="top.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, 2020:</div>

<div><br/></div>

<table cellpadding="0" cellspacing="0" id="zb8b331d548474cfd89ae511966ada4d1" 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;">One year 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;">73</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 one year but within two years</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;">18</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </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 two years but within <span style="-sec-ix-hidden:Fact_5b50da2d62974df399b2ebfcfccf0c30">three and a half years</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;">9</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 88%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">100</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
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</td>
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<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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" id="zb7472965e89a4156a0a9d32fd3eb5bf4" 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"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"/></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="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, 2020</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;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Cost </span>(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;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-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 (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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">514,182</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2,194</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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(41</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">516,335</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;">94,234</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;">354</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(2</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;">94,586</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 (2)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">307,576</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">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;">(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;">307,800</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 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;">104,271</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;">196</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;">(12</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;">104,455</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>
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  <tr>
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  <tr>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
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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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    <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"><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>
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  </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;">80,099</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>
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    <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;">(9</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>
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  </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;">50,318</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">383</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #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"><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;">50,697</div></td>
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  </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;">31,779</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;">91</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;">(16</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;">31,854</div></td>
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  </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;">1,041</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>
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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>
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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>
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  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total securities with a maturity of 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;">488,316</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>
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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>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></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;">493,847</div></td>
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  </tr>
  <tr>
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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; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
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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>
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    <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>
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  <tr>
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    <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;">Total equity securities included in other current assets (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"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4,712</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">(2,681</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;">2,031</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;">Total equity securities included in deposits and other assets (4)</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;">15,062</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;">15,938</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">31,000</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total 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;">19,774</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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">15,938</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">(2,681</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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">33,031</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total available-for-sale and equity securities</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">1,533,544</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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">24,515</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">(2,821</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;">1,555,238</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" id="za103de634c4d4cc69d2c374dfbfb01cd" 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"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"/></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="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>
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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; 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, 2019</div></td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><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>
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  <tr>
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  </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>
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    <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>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; 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: #FFFFFF;" valign="bottom">&#160;</td>
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  </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 (2)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
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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>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(27</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;">327,875</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </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;">21,065</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>
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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;">(5</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;">21,086</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total securities with a maturity of one year or less</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
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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;">2,012</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">&#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;">(118</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;">1,208,510</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;">428,627</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2,911</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;">(43</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;">431,495</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;">140,988</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">57</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" 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%; background-color: #CCEEFF; white-space: nowrap;" valign="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;">140,928</div></td>
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  </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;">35,822</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;">9</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>
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    <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;">35,819</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>
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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;">18</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>
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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;">19,321</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total securities with a maturity of 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;">624,746</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;">2,995</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;">(178</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;">627,563</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total 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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,831,362</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">5,007</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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(296</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">1,836,073</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; 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;">Total equity securities included in other current assets (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"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4,712</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(870</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">3,842</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;">Total equity securities included in deposits and other assets (4)</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;">10,000</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10,000</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total 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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">14,712</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">&#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"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(870</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">13,842</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; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total available-for-sale and equity securities</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,846,074</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">5,007</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>
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  </tr>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">________________</div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z61f6c267d21144238581ae579b649dc5" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
  <tr>
    <td style="width: 36pt; vertical-align: top; align: right; 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;">We hold our available-for-sale securities at amortized cost.</div></td>
  </tr>
</table>

<div><br/></div>

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  <tr>
    <td style="width: 36pt; vertical-align: top; align: right; 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;">Includes investments classified as cash equivalents on our consolidated balance sheet.</div></td>
  </tr>
</table>

<div><br/></div>

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  <tr>
    <td style="width: 36pt; vertical-align: top; align: right; 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 equity securities included in other current assets consisted of our investments in publicly traded companies. We recognize publicly traded equity securities at fair value.</div></td>
  </tr>
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<div><br/></div>

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  <tr>
    <td style="width: 36pt; vertical-align: top; align: right; 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;">Our equity securities included in deposits and other assets consisted of our investments in privately held companies. We recognize our private company equity securities at</span> cost minus impairments, plus or minus changes resulting from observable price changes in orderly transactions for the identical or similar investment of the same issuer<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> on our consolidated balance sheet.</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="top.Show.showAR( this, 'defref_us-gaap_ScheduleOfTemporaryImpairmentLossesInvestmentsTableTextBlock', window );">Temporarily Impaired Investments</a></td>
<td class="text">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">The </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">following is a summary of our investments we considered to be temporarily impaired at</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#160;</span>December 31, 2020<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;">(in thousands). All of these investments have less than 12 months of temporary impairment. </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We believe that the decline in value of these securities is temporary and is primarily related to the change in market interest rates since purchase. We believe it is more likely than not that we will be able to hold our debt securities to maturity. Therefore, we anticipate full recovery of our debt securities&#8217; amortized cost basis at maturity.</span></div>

<div><br/></div>

<table cellpadding="0" cellspacing="0" id="z0c03d0d401314f14abb08017a2d22100" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </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;">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>
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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;">$</div></td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">(81</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 64%;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 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%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="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">&#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;">29,988</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</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: 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;">8</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">76,941</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(13</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 64%;" valign="bottom"><div style="text-align: left; text-indent: -11.2pt; margin-left: 11.2pt; 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%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">160</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;">49,832</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;">(28</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: left; 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;">2</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" 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;">6,225</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"><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: 4px;" 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;" 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>
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    <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;">284,148</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>
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    <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;">(140</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>
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</table>
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<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
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<a href="javascript:void(0);" onclick="top.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>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
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<span style="display: none;">v3.20.4</span><table class="report" border="0" cellspacing="2" id="idm140142735058712">
<tr>
<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, 2020</div></th></tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_DebtDisclosureAbstract', window );"><strong>Long-Term Obligations and Commitments [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
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<tr class="ro">
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<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The carrying value of our long-term obligations was as follows (in thousands):</div>

<div><br/></div>

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    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/></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;">2020</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;">2019</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;">0.125 percent 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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">455,719</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">434,711</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
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  <tr>
    <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;">1 percent convertible senior notes (1)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">293,161</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;">275,333</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Long-term mortgage debt</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">59,984</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">59,913</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
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  <tr>
    <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;">Leases and other obligations</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;">30,710</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;">17,569</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%; 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</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">839,574</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">787,526</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; 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;">Less: current portion (1)</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;">(300,462</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;">(2,026</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: 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; 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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">539,112</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">785,500</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">________________</div>

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  <tr>
    <td style="width: 36pt; vertical-align: top; align: right; 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;">We classified the carrying value of our 1% Notes as a current liability on our consolidated balance sheet at December 31, 2020 because it matures in November 2021.</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="top.Show.showAR( this, 'defref_us-gaap_ConvertibleDebtTableTextBlock', window );">Convertible 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, 2020, we had the following <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">0.125%</span> Notes outstanding (amounts in millions except price per share data):</div>

<div><br/></div>

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  <tr>
    <td style="vertical-align: top; padding-bottom: 2px; white-space: nowrap;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/></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;">0.125% <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Notes</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: top; width: 88%; background-color: #CCEEFF; white-space: nowrap;" 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; 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;">548.8</div></td>
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  </tr>
  <tr>
    <td style="vertical-align: top; white-space: nowrap;" 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; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: top;" valign="bottom"><div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">December 15, 2024</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 88%; background-color: #CCEEFF; white-space: nowrap;" 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%; 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;">0.125</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%; white-space: nowrap;" 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%; white-space: nowrap;" valign="bottom">&#160;</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; text-align: right; width: 9%; white-space: nowrap;" 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; white-space: nowrap;" 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; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6.6</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
</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 table summarizes information about the equity and liability components of our outstanding </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">0.125%</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> Notes (in millions). We measured the fair values of the convertible notes outstanding based on quoted market prices, which is a Level 2 measurement at December 31, </span>2020<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> and </span>2019<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">:</span></div>

<div><br/></div>

<table cellpadding="0" cellspacing="0" id="z9adf776942de41cfa98e122ffee7ca9c" 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"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/></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; text-indent: 16pt;">2020</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;">2019</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;">Fair value of outstanding 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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">564.9</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">558.7</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>
  <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;">Principal amount of convertible notes outstanding</div></td>
    <td colspan="1" 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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">548.8</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">548.8</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;">Unamortized portion of debt discount</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">86.0</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">105.2</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 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 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"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">455.7</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">434.7</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: 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;">Carrying value of equity component</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">105.8</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">105.8</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
</table>

<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">At December 31, 2020, we had the following 1% Notes outstanding (amounts in millions except price per share data):</div>

<div><br/></div>

<table cellpadding="0" cellspacing="0" id="z7c00b82b222848c08f211e04a12df732" 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; white-space: nowrap;" valign="bottom"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/></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;">1% 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; white-space: nowrap;" 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; 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;">309.9</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: top; white-space: nowrap;" 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; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: top;" valign="bottom"><div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">November 30, 2021</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; background-color: #CCEEFF; white-space: nowrap;" 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; background-color: #CCEEFF; white-space: nowrap;" 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;">1 percent</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 88%; white-space: nowrap;" 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%; white-space: nowrap;" valign="bottom">&#160;</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; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">66.81</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; white-space: nowrap;" 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; 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;">4.6</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
</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;">The following table summarizes information about the equity and liability components of our outstanding </span>1%<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> Notes (in millions). We measured the fair values of the convertible notes outstanding based on quoted market prices, which is a Level 2 measurement at December 31, </span>2020<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> and </span>2019<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">:</span></div>

<div><br/></div>

<table cellpadding="0" cellspacing="0" id="z6aaac47fd8de480782bc6ae69dceb20c" 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"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/></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; text-indent: 16pt;">2020</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;">2019</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;">Fair value of outstanding 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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">338.5</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">354.8</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: 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;">Principal amount of convertible notes outstanding</div></td>
    <td colspan="1" 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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">309.9</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">309.9</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;">Unamortized portion of debt discount</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">15.8</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">32.8</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: 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;">Current/long-term 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"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">293.2</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">275.3</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: 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;">Carrying value of equity component</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">33.5</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">33.5</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>
</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 account for our convertible notes using an accounting standard that requires us to assign a value to our convertible debt equal to the estimated fair value of similar debt instruments without the conversion feature and to record the remaining portion in equity. As a result, we recorded our convertible notes at a discount, which we are amortizing as additional non-cash interest expense over the expected life of the respective debt. We determined our nonconvertible debt borrowing rate using a combination of the present value of the debt&#8217;s cash flows and a Black-Scholes valuation model. The following table summarizes the nonconvertible borrowing rate, effective interest rate and amortization period of our debt discount for our convertible notes:</div>

<div><br/></div>

<table cellpadding="0" cellspacing="0" id="z2fe2c231c3944d6a8692011908bb0bdd" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
  <tr>
    <td style="width: 39.54%; vertical-align: bottom;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"/></td>
    <td style="width: 2.25%; vertical-align: bottom;">&#160;</td>
    <td style="width: 28.82%; vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">1% Notes</div></td>
    <td style="width: 1.39%; vertical-align: top;">&#160;</td>
    <td style="width: 28%; 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;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">0.125%</span> Notes</div></td>
  </tr>
  <tr>
    <td style="width: 39.54%; vertical-align: bottom; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Nonconvertible debt borrowing rate</div></td>
    <td style="width: 2.25%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 28.82%; vertical-align: bottom; background-color: #CCEEFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">7.4 percent</div></td>
    <td style="width: 1.39%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 28%; vertical-align: bottom; background-color: #CCEEFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4.4 percent</div></td>
  </tr>
  <tr>
    <td style="width: 39.54%; vertical-align: bottom; background-color: #FFFFFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Effective interest rate (1)</div></td>
    <td style="width: 2.25%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 28.82%; vertical-align: bottom; background-color: #FFFFFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">7.5 percent</div></td>
    <td style="width: 1.39%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 28%; vertical-align: bottom; background-color: #FFFFFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4.9 percent</div></td>
  </tr>
  <tr>
    <td style="width: 39.54%; vertical-align: bottom; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Amortization period of debt discount</div></td>
    <td style="width: 2.25%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 28.82%; vertical-align: bottom; background-color: #CCEEFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">7 years</div></td>
    <td style="width: 1.39%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 28%; vertical-align: bottom; background-color: #CCEEFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">5 years</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" id="zfe3e4e94d24b42be98cc86e80ead96fa" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
  <tr>
    <td style="width: 36pt; vertical-align: top; align: right; 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;">For our 1% Notes, our effective interest rate represents our effective interest rate after our December 2019 debt exchange.</div></td>
  </tr>
</table>
<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_srt_ContractualObligationFiscalYearMaturityScheduleTableTextBlock', window );">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 debt and other obligation maturities, including fixed and determinable interest, at December 31, 2020 are as follows (in thousands):</div>

<div><br/></div>

<table cellpadding="0" cellspacing="0" id="z4c8baa70053148028f3836d3d205e2fe" 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;">2021</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">329,189</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;">2022</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3,495</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;">2023</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4,180</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;">2024</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">553,006</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;">2025</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3,494</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;">60,933</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;">Subtotal</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">954,297</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </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</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(300,462</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;">(21,758</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%;" valign="bottom"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Less: unamortized portion of debt discount</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(101,820</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: debt issuance costs</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(8,455</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;">Plus: lease liabilities</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;">17,310</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%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total long-term debt</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">539,112</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="top.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" id="z0a8a9123d7d24adcb53d3ae530505e1b" 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"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/></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;">At December 31, 2020</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 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 (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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">13.1</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
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    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">17.3</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: 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;">7.2 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;">7.0</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: 10pt;">________________</div>

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  <tr>
    <td style="width: 36pt; vertical-align: top; align: right; 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 <span style="-sec-ix-hidden:Fact_f81ca57385a04657b8ecd0f06d505159">deposits and other assets</span> on our consolidated balance sheet.</div></td>
  </tr>
</table>

<div><br/></div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="zd0fe2a08d108427ab40244fed97b9a07" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
  <tr>
    <td style="width: 36pt; vertical-align: top; align: right; 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;">Current portion of $2.0 million was included in <span style="-sec-ix-hidden:Fact_530181678e9244af8b37885d3ba85980">current portion of long-term obligations</span> on our consolidated balance sheet, with the difference included in <span style="-sec-ix-hidden:Fact_9c37cb3853f74a4f821bbe4ed37a06ba">long-term obligations</span>.</div></td>
  </tr>
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<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="top.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, 2020, the future payments for our operating lease liabilities are as follows (in thousands):</div>

<div><br/></div>

<table cellpadding="0" cellspacing="0" id="z04402bd2033b49df92fb5d8cb974b10a" 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"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/></td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Operating</span> <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Leases</span></div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;" 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; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">$</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: 88%;" valign="bottom"><div style="text-align: justify; margin-left: 18.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2021</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3,193</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;">2022</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2,968</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;">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;">2,707</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;">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">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2,583</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;">2025</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2,442</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%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: justify; 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; 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;">7,038</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: 88%;" 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%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">20,931</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: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">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">&#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: 88%; padding-bottom: 2px;" valign="bottom"><div style="text-align: left; margin-left: 18.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Imputed interest</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;">(3,621</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: left; margin-left: 36.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total operating lease 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;">17,310</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
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<span></span>
</td>
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<a href="javascript:void(0);" onclick="top.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="top.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="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher SEC<br> -Name Regulation S-K (SK)<br> -Number 229<br> -Section 303<br> -Paragraph (a)<br> -Subparagraph (5)<br></p></div>
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<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Tabular disclosure of borrowings which can be exchanged for a specified number of another security at the option of the issuer or the holder. Disclosures include, but are not limited to, principal amount, amortized premium or discount, and amount of liability and equity components.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.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="top.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="top.Show.toggleNext( this );">- Definition</a><div><p>Tabular disclosure of undiscounted cash flows of lessee's operating lease liability. Includes, but is not limited to, reconciliation of undiscounted cash flows to operating lease liability recognized in statement of financial position.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 842<br> -SubTopic 20<br> -Section 50<br> -Paragraph 6<br> -URI http://asc.fasb.org/extlink&amp;oid=121609121&amp;loc=SL77918701-209980<br></p></div>
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<span style="display: none;">v3.20.4</span><table class="report" border="0" cellspacing="2" id="idm140142732047304">
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<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Stockholders' Equity (Tables)<br></strong></div></th>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
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    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
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    <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; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>
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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%; padding-bottom: 4px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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  </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="top.Show.showAR( this, 'defref_us-gaap_ScheduleOfSharebasedCompensationRestrictedStockAndRestrictedStockUnitsActivityTableTextBlock', window );">RSU 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, 2020 (in thousands, except per share data):</div>

<div><br/></div>

<table cellpadding="0" cellspacing="0" id="zda6995a5dbd94d9990cbafed46af3aa1" 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"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/></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;">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;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Weighted Average</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Grant Date Fair</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Value Per Share</div></td>
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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;">Non-vested at December 31, 2019</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #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>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">55.80</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 76%;" valign="bottom"><div style="text-align: justify; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Granted</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">60.86</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>
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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"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">53.68</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 76%; padding-bottom: 2px;" valign="bottom"><div style="text-align: justify; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Cancelled/forfeited</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(134</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">58.96</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;">Non-vested at December 31, 2020</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2,374</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;">58.81</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="top.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, 2020, 2019 and 2018 (in thousands):</div>

<div><br/></div>

<table cellpadding="0" cellspacing="0" id="zf582273af94a47d4a55e546cbe3c3f20" 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"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/></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;">2020</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;">2019</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;">2018</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 products sold</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,991</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">438</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">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>
  </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;">115,584</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;">95,348</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;">76,557</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;">112,542</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; 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;">50,788</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;">54,595</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;">230,117</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">146,574</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">131,312</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="top.Show.showAR( this, 'defref_ions_ShareBasedCompensationLineItems', window );"><strong>Stockholders' Equity [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="top.Show.showAR( this, 'defref_us-gaap_ScheduleOfShareBasedPaymentAwardStockOptionsValuationAssumptionsTableTextBlock', window );">Weighted-Average Assumptions for Stock Options</a></td>
<td class="text">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Ionis Employee Stock Options:</div>

<div><br/></div>

<table cellpadding="0" cellspacing="0" id="z5de1b8387f794ea89da0aaf36c178756" 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"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/></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>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2020</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <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;">2019</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;">2018</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Risk-free interest rate</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1.5</div></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 colspan="1" style="vertical-align: bottom; width: 1%; background-color: #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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  </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>
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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;">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;">58.6</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">60.3</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;">63.0</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;">4.7 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;">4.8 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;">4.6 years</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
</table>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Ionis Board of Director Stock Options:</div>

<div><br/></div>

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  <tr>
    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/></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;">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;">2020</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;">2019</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;">2018</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;">0.5</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1.9</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;">2.8</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 64%;" valign="bottom"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Dividend yield</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.0</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.0</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.0</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Volatility</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">57.6</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">60.7</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;">61.5</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;" 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;">6.7 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;">6.6 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;">6.6 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="top.Show.showAR( this, 'defref_us-gaap_ScheduleOfShareBasedPaymentAwardEmployeeStockPurchasePlanValuationAssumptionsTableTextBlock', window );">Weighted-Average Assumptions for ESPP</a></td>
<td class="text">
<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Ionis ESPP:</div>

<div><br/></div>

<table cellpadding="0" cellspacing="0" id="z85916d3a965048b191b56294e70d2310" 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"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/></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;">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;">2020</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;">2019</div></td>
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<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="top.Show.showAR( this, 'defref_srt_ConsolidatedEntitiesAxis=ions_AkceaTherapeuticsIncMember', window );">Akcea [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="top.Show.showAR( this, 'defref_ions_ShareBasedCompensationLineItems', window );"><strong>Stockholders' Equity [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="top.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;">Akcea Employee Stock Options:</div>

<div><br/></div>

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    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
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  <tr>
    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #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>
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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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  </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>
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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;">0.0</div></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"><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>
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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="text-align: left; vertical-align: bottom; 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>
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  </tr>
  <tr>
    <td style="vertical-align: bottom;" valign="bottom"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Expected life</div></td>
    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom;" valign="bottom"><div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6.08 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;">Akcea Board of Director Stock Options:</div>

<div><br/></div>

<table cellpadding="0" cellspacing="0" id="z65411e08eef04f55b90f91e957d37dce" 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"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/></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;">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;">2020</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;">2019</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;">2018</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>
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<span></span>
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<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;">Akcea ESPP:</div>

<div><br/></div>

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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
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<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Tabular disclosure for stock option plans. Includes, but is not limited to, outstanding awards at beginning and end of year, grants, exercises, forfeitures, and weighted-average grant date fair value.</p></div>
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<span style="display: none;">v3.20.4</span><table class="report" border="0" cellspacing="2" id="idm140142732977192">
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Income (loss) before income taxes is comprised of (in thousands):</div>

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    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2019</div></td>
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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>
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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>
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<div><br/></div>

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    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
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  <tr>
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    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom;" 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;">Federal</div></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="text-align: left; vertical-align: bottom; 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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">35,861</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">438</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;">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;">3,782</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">14,329</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(1,442</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;">518</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; 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;">413</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;">374</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;">3,463</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;">50,603</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;">(630</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;">313,271</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(7,096</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;">(290,511</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;">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;">313,271</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;">(7,096</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;">(290,511</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 64%; 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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">316,734</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">43,507</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;">(291,141</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="top.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: justify; 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 income (loss) before taxes. The sources and tax effects of the differences are as follows (in thousands):</div>

<div><br/></div>

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    <td colspan="2" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>
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    <td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>
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    <td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>
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    <td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>
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    <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>
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    <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>
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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="text-align: left; vertical-align: bottom; 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>
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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="vertical-align: bottom; width: 1%; background-color: #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"><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>
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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"><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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    <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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    <td colspan="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%;" 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>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
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  <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>
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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; width: 1%; background-color: #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>
    <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>
    <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>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
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    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
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    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">364.9</div></td>
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  <tr>
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  <tr>
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  <tr>
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  </tr>
  <tr>
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  <tr>
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  </tr>
  <tr>
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  </tr>
  <tr>
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  </tr>
  <tr>
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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; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
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  </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;">Impacts from Akcea Acquisition</div></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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  </tr>
  <tr>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>
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  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 28%; 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;">Effective rate</div></td>
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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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  </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="top.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, 2020 and 2019 are as follows (in thousands):</div>

<div><br/></div>

<table cellpadding="0" cellspacing="0" id="zae724c9b7f994507b05f251f1d96b8e5" 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="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
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  <tr>
    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
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  <tr>
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    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
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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;">83,681</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">20,191</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>
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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;">210,455</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>
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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>
  </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;">80,055</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;">65,703</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;">98,443</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">77,861</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </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;">13,402</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;">12,510</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 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;">645,779</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">514,483</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;">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"><div style="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;">(2,920</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;">(6,110</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;">Fixed 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;">(3,611</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;">(1,958</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </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;">(5,808</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;">(3,884</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;">633,440</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">502,531</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;">(633,440</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;">(196,974</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;">305,557</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="top.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 (in thousands):</div>

<div><br/></div>

<table cellpadding="0" cellspacing="0" id="z20fa178d8de346858dcbfb940644c973" 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"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/></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;">2020</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;">2019</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;">2018</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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">69,784</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">68,301</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">78,014</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: 64%;" valign="bottom"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Decrease for prior period tax positions</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(24,154</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(867</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(12,814</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Increase for prior period tax positions</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">7,023</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">736</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-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;">Increase for current period tax positions</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,510</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <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;">1,614</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;">3,101</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 64%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Ending balance of unrecognized tax benefits</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">54,163</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">69,784</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">68,301</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
</table>
<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_IncomeTaxDisclosureAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_IncomeTaxDisclosureAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ScheduleOfComponentsOfIncomeTaxExpenseBenefitTableTextBlock">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Tabular disclosure of the components of income tax expense attributable to continuing operations for each year presented including, but not limited to: current tax expense (benefit), deferred tax expense (benefit), investment tax credits, government grants, the benefits of operating loss carryforwards, tax expense that results from allocating certain tax benefits either directly to contributed capital or to reduce goodwill or other noncurrent intangible assets of an acquired entity, adjustments of a deferred tax liability or asset for enacted changes in tax laws or rates or a change in the tax status of the entity, and adjustments of the beginning-of-the-year balances of a valuation allowance because of a change in circumstances that causes a change in judgment about the realizability of the related deferred tax asset in future years.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 9<br> -URI http://asc.fasb.org/extlink&amp;oid=84230637&amp;loc=d3e32639-109319<br></p></div>
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<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Tabular disclosure of the components of net deferred tax asset or liability recognized in an entity's statement of financial position, including the following: the total of all deferred tax liabilities, the total of all deferred tax assets, the total valuation allowance recognized for deferred tax assets.</p></div>
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<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Tabular disclosure of the reconciliation using percentage or dollar amounts of the reported amount of income tax expense attributable to continuing operations for the year to the amount of income tax expense that would result from applying domestic federal statutory tax rates to pretax income from continuing operations.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 12<br> -URI http://asc.fasb.org/extlink&amp;oid=84230637&amp;loc=d3e32687-109319<br></p></div>
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">- Definition</a><div><p>Tabular disclosure of income before income tax between domestic and foreign jurisdictions.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 235<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.4-08.(h)(1)(i))<br> -URI http://asc.fasb.org/extlink&amp;oid=120395691&amp;loc=d3e23780-122690<br></p></div>
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<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Tabular disclosure of the change in unrecognized tax benefits.</p></div>
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<span style="display: none;">v3.20.4</span><table class="report" border="0" cellspacing="2" id="idm140142740656872">
<tr>
<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>
</tr>
<tr><th class="th"><div>Dec. 31, 2020</div></th></tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementsAndLicensingAgreementsBiogenMember', window );">Biogen [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="top.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="top.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, 2020, 2019 and 2018, we earned the following revenue from our relationship with Biogen (in millions, except percentage amounts):</div>

<div><br/></div>

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    <td colspan="10" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Year Ended December 31,</div></td>
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    <td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -27pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">SPINRAZA royalties (commercial revenue)</div></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;">237.9</div></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="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">122.0</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <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;">180.6</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;">137.1</div></td>
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    <td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total revenue from our relationship with Biogen</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></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"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">375.0</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 64%;" valign="bottom"><div style="text-align: left; 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;">56</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">42</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;">63</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>
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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="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementsAndLicensingAgreementsAstrazenecaMember', window );">AstraZeneca [Member]</a></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="top.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="top.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, 2020, 2019 and 2018, we earned the following revenue from our relationship with AstraZeneca (in millions, except percentage amounts):</div>

<div><br/></div>

<table cellpadding="0" cellspacing="0" id="z01afabad46534511a6a9d546d3508d28" 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"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/></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>
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  <tr>
    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: 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;">2019</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;">2018</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -27pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">R&amp;D revenue</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">28.1</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></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>
  </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;">12</div></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"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">20</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="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementsAndLicensingAgreementsBayerMember', window );">Bayer [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="top.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="top.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, 2020, 2019 and 2018, we earned the following revenue from our relationship with Bayer (in millions, except percentage amounts):</div>

<div><br/></div>

<table cellpadding="0" cellspacing="0" id="z9c944936e6cb48bf94b3cd80005a253e" 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"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/></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;">2020</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;">2019</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;">2018</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -27pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">R&amp;D revenue</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3.2</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">14.3</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">5.0</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 64%;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Percentage of total revenue</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">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;">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;">1</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
</table>
<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGlaxoSmithKlineMember', window );">GSK [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="top.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="top.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, 2020, 2019 and 2018, we earned the following revenue from our relationship with GSK (in millions, except percentage amounts):</div>

<div><br/></div>

<table cellpadding="0" cellspacing="0" id="zd82f932b4364444296f6727d4a1a1d5e" 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"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/></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;">2020</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;">2019</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;">2018</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -27pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">R&amp;D revenue</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.2</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">25.4</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1.6</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 64%;" valign="bottom"><div style="text-align: left; 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;">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;">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>
  </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="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2014WithJanssenBiotechIncMember', window );">Janssen Biotech, Inc. [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="top.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="top.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, 2020, 2019 and 2018, we earned the following revenue from our relationship with Janssen (in millions, except percentage amounts):</div>

<div><br/></div>

<table cellpadding="0" cellspacing="0" id="z214ec07483da45419ff12bf6494b6cc8" 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"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/></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>
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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;">2019</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;">2018</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -27pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">R&amp;D revenue</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">0.1</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6.6</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 64%;" valign="bottom"><div style="text-align: left; 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;">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;">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;">1</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
</table>
<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember', 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="top.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="top.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, 2020 and 2019, we earned the following revenue from our relationship with Novartis (in millions, except percentage amounts):</div>

<div><br/></div>

<table cellpadding="0" cellspacing="0" id="zbc240042123541949eac40f85586e85a" 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"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/></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;">2020</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;">2019</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;">2018</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -27pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">R&amp;D revenue</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1.0</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">187.4</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">50.6</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 64%;" valign="bottom"><div style="text-align: left; 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;">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;">17</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;">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>
  </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="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2019WithPfizerMember', window );">Pfizer [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="top.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="top.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, 2020 and 2019, we earned the following revenue from our relationship with Pfizer (in millions, except percentage amounts):</div>

<div><br/></div>

<table cellpadding="0" cellspacing="0" id="z6cd9b1a78b1f4646b6991f4b40434cd7" 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"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/></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;">2020</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;">2019</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: -27pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">R&amp;D revenue</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">82.1</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">248.7</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>
  <tr>
    <td style="vertical-align: bottom; width: 76%;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Percentage of total revenue</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">11</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">22</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="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInAugust2018WithPtcTherapeuticsMember', window );">PTC Therapeutics [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="top.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="top.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, 2020, 2019 and 2018, we earned the following revenue from our relationship with PTC (in millions, except percentage amounts):</div>

<div><br/></div>

<table cellpadding="0" cellspacing="0" id="z00af651f87dd4ff3a8aa829ed62a0b47" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
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    <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>
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  <tr>
    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2020</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <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;">2019</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;">2018</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;">Licensing and other royalty revenue (commercial revenue)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1.6</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.2</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">12.0</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 64%;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Percentage of total revenue</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">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;">1</div></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"><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="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementsAndLicensingAgreementsRocheMember', window );">Roche [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="top.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, 2020, 2019 and 2018, we earned the following revenue from our relationship with Roche (in millions, except percentage amounts):</div>

<div><br/></div>

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  <tr>
    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/></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;">2020</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;">2019</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;">2018</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -27pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">R&amp;D revenue</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">5.9</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">57.0</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">8.3</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </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;">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;">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;">1</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
</table>
<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_AlnylamPharmaceuticalsIncMember', window );">Alnylam Pharmaceuticals, Inc. [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="top.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="top.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;">In the fourth quarter 2020, we completed an arbitration process with Alnylam. The arbitration panel awarded us $41.2 million for payments owed to us by Alnylam related to Alnylam&#8217;s agreement with Sanofi Genzyme. We recognized the $41.2 million payment from Alnylam as revenue in the fourth quarter of 2020 because we did not have any performance obligations for the respective payment.</div>

<div><br/></div>

<table cellpadding="0" cellspacing="0" id="ze601d61823704755a02ce987dfe37676" 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"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/></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;">2020</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;">2019</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;">2018</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -27pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">R&amp;D revenue</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">47.9</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">24.1</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2.0</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 64%;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Percentage of total revenue</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">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</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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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
</table>
<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems">
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<a href="javascript:void(0);" onclick="top.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>
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<div style="text-align: justify; text-indent: 36pt; margin-top: 2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following table summarizes the costs by category related to the Akcea Acquisition (in millions):</div>

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

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    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3.9</div></td>
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    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">11.4</div></td>
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    <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>
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<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; margin-top: 2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following table summarizes the severance and retention reserve included in accrued compensation for the period indicated related to Akcea Acquisition (in millions):</div>

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

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<span style="display: none;">v3.20.4</span><table class="report" border="0" cellspacing="2" id="idm140142822192360">
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<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Severance and Retention Costs related to our Restructured European Operations (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 table summarizes the costs by category related to our restructured European operations (in millions):</div>

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

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    <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;">8.3</div></td>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following table summarizes the severance and retention reserve included in accrued compensation for the periods indicated related to our restructured European operations (in millions):</div>

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

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<span style="display: none;">v3.20.4</span><table class="report" border="0" cellspacing="2" id="idm140142740867208">
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<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Segment Information and Concentration of Business Risk (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, 2020</div></th></tr>
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<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_SegmentReportingAbstract', window );"><strong>Segment Information and Concentration of Business Risk [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="top.Show.showAR( this, 'defref_us-gaap_ScheduleOfSegmentReportingInformationBySegmentTextBlock', window );">Segment Information</a></td>
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<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">The following tables show our segment revenue and income (loss) from operations for </span>2020, 2019 and 2018<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> (in thousands), respectively.</span></div>

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<table cellpadding="0" cellspacing="0" id="zef53d7fefabb427795be91924081cd7f" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td style="vertical-align: bottom; border-bottom: #000000 2px solid; white-space: nowrap;" valign="bottom"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2020</div></td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Ionis Core</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;">Akcea Therapeutics</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;">Elimination of</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Intercompany Activity</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;">Total</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; white-space: nowrap;" valign="bottom"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Revenue:</div></td>
    <td colspan="1" style="vertical-align: bottom; 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; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; 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; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; 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; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; 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; white-space: nowrap;" valign="bottom">&#160;</td>
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  <tr>
    <td style="vertical-align: top; white-space: nowrap;" valign="bottom"><div style="text-align: left; margin-left: 7.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Commercial revenue:</div></td>
    <td colspan="1" style="vertical-align: bottom; 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; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; 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; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; 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; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; 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; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 52%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="text-align: left; margin-left: 25.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">SPINRAZA royalties</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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">286,583</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">&#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; 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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">286,583</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: 52%; white-space: nowrap;" valign="bottom"><div style="text-align: left; margin-left: 25.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Product sales, net</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;">&#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%; 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;">69,999</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;">&#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%; 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;">69,999</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: 52%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="text-align: left; margin-left: 25.2pt; 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; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">11,334</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(3,217</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">8,117</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: top; width: 52%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"><div style="text-align: left; margin-left: 43.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total commercial revenue</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;">297,917</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;">69,999</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;">(3,217</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;">364,699</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: top; width: 52%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="text-align: left; margin-left: 7.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">R&amp;D revenue under collaborative agreements</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">325,024</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">82,321</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(42,780</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">364,565</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: top; width: 52%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"><div style="text-align: left; margin-left: 25.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total segment revenue</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
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  <tr>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
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    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">389,575</div></td>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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    <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;">$</div></td>
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  </tr>
  <tr>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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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; white-space: nowrap;" valign="bottom">&#160;</td>
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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; white-space: nowrap;" valign="bottom">&#160;</td>
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    <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><br/></div>

<table cellpadding="0" cellspacing="0" id="zd5bde97ab66c4903be53b04e577e42d6" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
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    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
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    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Akcea Therapeutics</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
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    <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; 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; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; 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; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; 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; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
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    <td colspan="1" style="vertical-align: bottom; 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; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; 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; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; 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; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; 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; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 52%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="text-align: left; margin-left: 25.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">SPINRAZA royalties</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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">292,992</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">&#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; 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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">292,992</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: 52%; white-space: nowrap;" valign="bottom"><div style="text-align: left; margin-left: 25.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Product sales, net</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;">&#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%; 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;">42,253</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;">&#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%; 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;">42,253</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: 52%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="text-align: left; margin-left: 25.2pt; 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; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">12,616</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10,172</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(5,583</div></td>
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    <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>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; 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%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
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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="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
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    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">770,149</div></td>
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  <tr>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
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  <tr>
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    <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;">$</div></td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">450,469</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;">$</div></td>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">756,716</div></td>
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  <tr>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
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    <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>
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<div><br/></div>

<table cellpadding="0" cellspacing="0" id="zfeba46abdf4c46b192c4196f9b159018" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
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    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
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    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>
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    <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; white-space: nowrap;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>
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  <tr>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; 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; white-space: nowrap;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>
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  <tr>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; 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>
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  <tr>
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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>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
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  <tr>
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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; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
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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; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
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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; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">14,755</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>
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  <tr>
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    <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>
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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; 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;">14,237</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;">&#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; 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;">254,922</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 52%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="text-align: left; margin-left: 7.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">R&amp;D revenue under collaborative agreements</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">401,259</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">50,630</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(107,137</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">344,752</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: top; width: 52%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"><div style="text-align: left; margin-left: 25.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total segment revenue</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">641,944</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">64,867</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(107,137</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">599,674</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>
  <tr>
    <td style="vertical-align: top; width: 52%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total operating expenses</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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">380,212</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">295,683</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>
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    <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;">(14,849</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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">661,046</div></td>
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  </tr>
  <tr>
    <td style="vertical-align: top; width: 52%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"><div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Income (loss) from operations</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">261,732</div></td>
    <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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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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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;">The following table shows our total assets by segment at December 31, 2020 and 2019 (in thousands), respectively.</div>

<div><br/></div>

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    <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;">Elimination of</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Intercompany Activity</div></td>
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    <td colspan="2" style="vertical-align: bottom; border-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</div></td>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
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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>
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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 for a fair statement of the results of the interim periods. Summarized fourth quarter data for 2020 and 2019 are as follows (in thousands, except per share data).</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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">260,652</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 76%;" valign="bottom"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net income (loss)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">(341,426</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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">203,957</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net income (loss) attributable to Ionis Pharmaceuticals, Inc. common stockholders</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">184,415</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 76%;" valign="bottom"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Basic net income (loss) per share (1) (2)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">(2.44</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"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1.31</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Diluted net income (loss) per share (1) (3)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(2.44</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1.28</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: 10pt;">________________</div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z95fc0fe83dcc44d3beffd99343c41418" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
  <tr>
    <td style="width: 36pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(1)</td>
    <td style="width: auto; vertical-align: top; text-align: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We </span>compute net income (loss) per share independently for each quarter during <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">the year.</span></div></td>
  </tr>
</table>

<div><br/></div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z7f159b28bab545f4b7ef06cc58aafa2d" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
  <tr>
    <td style="width: 36pt; vertical-align: top; align: right; 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;">As discussed in Note 1, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Organization and Significant Accounting Policies, </span>we compute basic net income (loss) per share by dividing the total net income (loss) attributable to our common stockholders by our weighted-average number of common shares outstanding during the period. Our basic net income (loss) per share calculation for each of the fourth quarters in 2020 and 2019 considered our net income (loss) for Ionis on a stand-alone basis plus our share of Akcea&#8217;s net loss for the period. To calculate the portion of Akcea&#8217;s net loss attributable to our ownership, we multiplied Akcea&#8217;s loss per share by the weighted average shares we owned in Akcea during the period. As a result of this calculation, our total net income (loss) available to Ionis common stockholders for the calculation of net income (loss) per share is different than net income (loss) attributable to Ionis Pharmaceuticals, Inc. common stockholders in the consolidated statements of operations.</div></td>
  </tr>
</table>

<div><br/></div>

<div style="text-align: justify; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our basic net income (loss) per share the quarter referenced was calculated as follows (in thousands, except per share amounts):</div>

<div><br/></div>

<table cellpadding="0" cellspacing="0" id="z575ab3fcea8448b08361487272ec926a" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td style="vertical-align: bottom; border-bottom: #000000 2px solid; white-space: nowrap;" valign="bottom"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Three Months Ended December 31 , 2020</div></td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Weighted</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Average Shares</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Owned in Akcea</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Akcea</span>&#8217;<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">s</span></div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Net Loss</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Per Share</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Basic Net Loss</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Per Share</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Calculation</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Akcea&#8217;s net loss in the pre-acquisition period attributable to our ownership</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">77,095</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(0.05</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">(3,603</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Akcea&#8217;s net loss in the post-acquisition period attributable to our ownership</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(85,987</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Akcea&#8217;s total net loss attributable to our ownership</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(89,590</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Ionis&#8217; stand-alone net loss</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(250,682</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net loss available to Ionis common stockholders</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
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  <tr>
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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; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
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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; white-space: nowrap;" valign="bottom">&#160;</td>
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  </tr>
  <tr>
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</table>

<div><br/></div>

<table cellpadding="0" cellspacing="0" id="z4d63d8880724435496c59a8fec3d2f7e" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
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    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Basic Net Income</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Per Share</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Calculation</div></td>
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  <tr>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
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    <td colspan="1" style="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="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">62,243</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: top; width: 64%; white-space: nowrap;" valign="bottom"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Akcea&#8217;s net income attributable to our ownership</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">&#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%; 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">&#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%; white-space: nowrap;" valign="bottom">&#160;</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; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">62,243</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: 64%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Ionis&#8217; stand-alone net income</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">121,552</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: top; width: 64%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net income available to Ionis common stockholders</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times 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; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">183,795</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Weighted average shares outstanding</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
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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: top; width: 64%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Basic net income per share</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1.31</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
</table>

<div><br/></div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z24e5fa74899b4127901c49f6468fa415" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
  <tr>
    <td style="width: 36pt; vertical-align: top; align: right; 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;">We had net income available to Ionis common stockholders for the fourth quarter of 2019. As a result, we computed diluted net income per share using the weighted-average number of common shares and dilutive common equivalent shares outstanding during the period as follows (in thousands except per share amounts):</div></td>
  </tr>
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<div><br/></div>

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<th class="tl" colspan="1" rowspan="1"><div style="width: 200px;"><strong>Organization and Significant Accounting Policies, Basis of Presentation (Details)<br></strong></div></th>
<th class="th"><div>Oct. 31, 2020</div></th>
<th class="th"><div>Sep. 30, 2020</div></th>
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<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_MinorityInterestOwnershipPercentageByParent', window );">Percentage ownership</a></td>
<td class="nump">100.00%<span></span>
</td>
<td class="nump">76.00%<span></span>
</td>
<td class="nump">100.00%<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_MinorityInterestOwnershipPercentageByParent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The parent entity's interest in net assets of the subsidiary, expressed as a percentage.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_MinorityInterestOwnershipPercentageByParent</td>
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<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>num:percentItemType</td>
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<td><strong> Balance Type:</strong></td>
<td>na</td>
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<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ProceedsFromIssuanceOrSaleOfEquityAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ProceedsFromIssuanceOrSaleOfEquityAbstract</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
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<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
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<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_srt_OwnershipAxis=ions_AkceaTherapeuticsIncMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">srt_OwnershipAxis=ions_AkceaTherapeuticsIncMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
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<DOCUMENT>
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<DESCRIPTION>IDEA: XBRL DOCUMENT
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<head>
<title></title>
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<span style="display: none;">v3.20.4</span><table class="report" border="0" cellspacing="2" id="idm140142740937976">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Organization and Significant Accounting Policies, Basic and Diluted Net Income (Loss) per Share (Details) - USD ($)<br> $ / shares in Units, shares in Thousands, $ in Thousands</strong></div></th>
<th class="th" colspan="1">2 Months Ended</th>
<th class="th" colspan="4">3 Months Ended</th>
<th class="th" colspan="1">10 Months Ended</th>
<th class="th" colspan="3">12 Months Ended</th>
</tr>
<tr>
<th class="th"><div>Dec. 31, 2020</div></th>
<th class="th" colspan="2"><div>Dec. 31, 2020</div></th>
<th class="th" colspan="2"><div>Dec. 31, 2019</div></th>
<th class="th"><div>Oct. 31, 2020</div></th>
<th class="th"><div>Dec. 31, 2020</div></th>
<th class="th"><div>Dec. 31, 2019</div></th>
<th class="th"><div>Dec. 31, 2018</div></th>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_EarningsPerShareBasicAbstract', window );"><strong>Basic Net Income (Loss) per Share [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_EarningsPerShareBasic', window );">Basic net income (loss) per share (in dollars per share)</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="num">$ (2.44)<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"><sup>[1],[2]</sup></td>
<td class="nump">$ 1.31<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"><sup>[1],[2]</sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="num">$ (3.23)<span></span>
</td>
<td class="nump">$ 2.12<span></span>
</td>
<td class="nump">$ 2.09<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_NetIncomeLoss', window );">Net income (loss)</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="num">$ (340,271)<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">$ 184,415<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="num">$ (451,286)<span></span>
</td>
<td class="nump">$ 294,146<span></span>
</td>
<td class="nump">$ 273,741<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_NetIncomeLossAvailableToCommonStockholdersBasic', window );">Net income (loss) available to Ionis common stockholders</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="num">$ (340,272)<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">$ 183,795<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="num">$ (451,487)<span></span>
</td>
<td class="nump">$ 296,563<span></span>
</td>
<td class="nump">$ 276,868<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_WeightedAverageNumberOfSharesOutstandingBasic', window );">Weighted average shares outstanding (in shares)</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">139,956<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">140,583<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">139,612<span></span>
</td>
<td class="nump">139,998<span></span>
</td>
<td class="nump">132,320<span></span>
</td>
</tr>
<tr class="rou">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_NetIncomeLossAvailableToCommonStockholdersDiluted', window );">Net income available to Ionis common shareholders</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">$ 196,485<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 296,563<span></span>
</td>
<td class="nump">$ 276,868<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_IncrementalCommonSharesAttributableToEmployeeStockPurchasePlan', window );">Shares issuable related to our ESPP (in shares)</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">18<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">18<span></span>
</td>
<td class="nump">6<span></span>
</td>
</tr>
<tr class="rou">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding', window );">Shares used in computing diluted net income per share (in shares)</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">153,303<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">139,612<span></span>
</td>
<td class="nump">142,872<span></span>
</td>
<td class="nump">134,056<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_EarningsPerShareDiluted', window );">Diluted net income per share (in dollars per share)</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="num">$ (2.44)<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"><sup>[2],[3]</sup></td>
<td class="nump">$ 1.28<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"><sup>[2],[3]</sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="num">$ (3.23)<span></span>
</td>
<td class="nump">$ 2.08<span></span>
</td>
<td class="nump">$ 2.07<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_EarningsPerShareBasicAbstract', window );"><strong>Basic Net Income (Loss) per Share [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_DebtInstrumentInterestRateStatedPercentage', window );">Interest rate on convertible senior notes</a></td>
<td class="nump">0.125%<span></span>
</td>
<td class="nump">0.125%<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">0.125%<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">0.125%<span></span>
</td>
<td class="nump">0.125%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_EarningsPerShareBasicAbstract', window );"><strong>Basic Net Income (Loss) per Share [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_DebtInstrumentInterestRateStatedPercentage', window );">Interest rate on convertible senior notes</a></td>
<td class="nump">1.00%<span></span>
</td>
<td class="nump">1.00%<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">1.00%<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">1.00%<span></span>
</td>
<td class="nump">1.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AwardTypeAxis=us-gaap_EmployeeStockOptionMember', window );">Stock Options [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_EarningsPerShareBasicAbstract', window );"><strong>Basic Net Income (Loss) per Share [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_IncrementalCommonSharesAttributableToShareBasedPaymentArrangements', window );">Shares issuable related to stock-based compensation (in shares)</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">1,467<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">2,090<span></span>
</td>
<td class="nump">1,216<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AwardTypeAxis=us-gaap_RestrictedStockMember', window );">Restricted Stock Awards [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_EarningsPerShareBasicAbstract', window );"><strong>Basic Net Income (Loss) per Share [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_IncrementalCommonSharesAttributableToShareBasedPaymentArrangements', window );">Shares issuable related to stock-based compensation (in shares)</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">848<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">766<span></span>
</td>
<td class="nump">514<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_StatementBusinessSegmentsAxis=ions_IonisCoreMember', window );">Ionis [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_EarningsPerShareBasicAbstract', window );"><strong>Basic Net Income (Loss) per Share [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
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<td class="text">&#160;<span></span>
</td>
<td class="num">$ (250,682)<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">$ 121,552<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="num">$ (253,725)<span></span>
</td>
<td class="nump">$ 262,490<span></span>
</td>
<td class="nump">$ 440,806<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_srt_ConsolidatedEntitiesAxis=ions_AkceaTherapeuticsIncMember', window );">Akcea [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_EarningsPerShareBasicAbstract', window );"><strong>Basic Net Income (Loss) per Share [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_NetIncomeLoss', window );">Net income (loss)</a></td>
<td class="num">$ (85,987)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="num">$ (197,762)<span></span>
</td>
<td class="nump">$ 34,073<span></span>
</td>
<td class="num">$ (163,938)<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_srt_ConsolidatedEntitiesAxis=ions_AkceaTherapeuticsIncMember', window );">Akcea [Member] | Common Stock [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_EarningsPerShareBasicAbstract', window );"><strong>Basic Net Income (Loss) per Share [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_WeightedAverageNumberOfSharesOwnedInSubsidiary', window );">Weighted average shares owned in Akcea (in shares)</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">77,095<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">70,100<span></span>
</td>
<td class="nump">59,812<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_EarningsPerShareBasic', window );">Basic net income (loss) per share (in dollars per share)</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="num">$ (1.45)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 0.49<span></span>
</td>
<td class="num">$ (2.74)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_NetIncomeLoss', window );">Net income (loss)</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="num">$ (111,775)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 34,073<span></span>
</td>
<td class="num">$ (163,938)<span></span>
</td>
</tr>
<tr><td colspan="10"></td></tr>
<tr><td colspan="10"><table class="outerFootnotes" width="100%">
<tr class="outerFootnote">
<td style="vertical-align: top; width: 12pt;" valign="top">[1]</td>
<td style="vertical-align: top;" valign="top">As discussed in Note 1, Organization and Significant Accounting Policies, we compute basic net income (loss) per share by dividing the total net income (loss) attributable to our common stockholders by our weighted-average number of common shares outstanding during the period. Our basic net income (loss) per share calculation for each of the fourth quarters in 2020 and 2019 considered our net income (loss) for Ionis on a stand-alone basis plus our share of Akcea&#8217;s net loss for the period. To calculate the portion of Akcea&#8217;s net loss attributable to our ownership, we multiplied Akcea&#8217;s loss per share by the weighted average shares we owned in Akcea during the period. As a result of this calculation, our total net income (loss) available to Ionis common stockholders for the calculation of net income (loss) per share is different than net income (loss) attributable to Ionis Pharmaceuticals, Inc. common stockholders in the consolidated statements of operations.</td>
</tr>
<tr class="outerFootnote">
<td style="vertical-align: top; width: 12pt;" valign="top">[2]</td>
<td style="vertical-align: top;" valign="top">We compute net income (loss) per share independently for each quarter during the year.</td>
</tr>
<tr class="outerFootnote">
<td style="vertical-align: top; width: 12pt;" valign="top">[3]</td>
<td style="vertical-align: top;" valign="top">We had net income available to Ionis common stockholders for the fourth quarter of 2019. As a result, we computed diluted net income per share using the weighted-average number of common shares and dilutive common equivalent shares outstanding during the period</td>
</tr>
</table></td></tr>
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<div style="display: none;">
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<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Additional shares included in the calculation of diluted EPS as a result of the potentially dilutive effect of shares issuable related to employee stock purchase plan.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">- Definition</a><div><p>Number of shares owned in the subsidiary during the reporting period determined by relating the portion of time within a reporting period that shares have been owned to the total time in that period.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.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="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02.22(a)(1))<br> -URI http://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">- Definition</a><div><p>The amount of net income (loss) for the period per each share of common stock or unit outstanding during the reporting period.</p></div>
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<a href="javascript:void(0);" onclick="top.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> Period Type:</strong></td>
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<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_EarningsPerShareBasicAbstract</td>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 55<br> -Paragraph 52<br> -URI http://asc.fasb.org/extlink&amp;oid=120380238&amp;loc=d3e4984-109258<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 250<br> -SubTopic 10<br> -Section 50<br> -Paragraph 7<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=109234566&amp;loc=d3e22644-107794<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 55<br> -Paragraph 15<br> -URI http://asc.fasb.org/extlink&amp;oid=120380238&amp;loc=d3e3842-109258<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 45<br> -Paragraph 2<br> -URI http://asc.fasb.org/extlink&amp;oid=121326447&amp;loc=d3e1252-109256<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 250<br> -SubTopic 10<br> -Section 50<br> -Paragraph 11<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=109234566&amp;loc=d3e22694-107794<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 250<br> -SubTopic 10<br> -Section 50<br> -Paragraph 4<br> -URI http://asc.fasb.org/extlink&amp;oid=109234566&amp;loc=d3e22595-107794<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 250<br> -SubTopic 10<br> -Section 50<br> -Paragraph 3<br> -URI http://asc.fasb.org/extlink&amp;oid=109234566&amp;loc=d3e22583-107794<br><br>Reference 8: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 45<br> -Paragraph 60B<br> -Subparagraph (d)<br> -URI http://asc.fasb.org/extlink&amp;oid=121326447&amp;loc=SL5780133-109256<br><br>Reference 9: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 942<br> -SubTopic 220<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-04(27))<br> -URI http://asc.fasb.org/extlink&amp;oid=120399700&amp;loc=SL114874048-224260<br><br>Reference 10: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=6371337&amp;loc=d3e3550-109257<br><br>Reference 11: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 944<br> -SubTopic 220<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-04(23))<br> -URI http://asc.fasb.org/extlink&amp;oid=120400993&amp;loc=SL114874131-224263<br><br>Reference 12: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 250<br> -SubTopic 10<br> -Section 50<br> -Paragraph 11<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=109234566&amp;loc=d3e22694-107794<br><br>Reference 13: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 45<br> -Paragraph 7<br> -URI http://asc.fasb.org/extlink&amp;oid=121326447&amp;loc=d3e1337-109256<br><br>Reference 14: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.5-03(25))<br> -URI http://asc.fasb.org/extlink&amp;oid=120395209&amp;loc=SL114868664-224227<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>num: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_IncrementalCommonSharesAttributableToShareBasedPaymentArrangements">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Additional shares included in the calculation of diluted EPS as a result of the potentially dilutive effect of share based payment arrangements using the treasury stock method.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 45<br> -Paragraph 22<br> -URI http://asc.fasb.org/extlink&amp;oid=121326447&amp;loc=d3e1707-109256<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=6371337&amp;loc=d3e3550-109257<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 45<br> -Paragraph 28A<br> -URI http://asc.fasb.org/extlink&amp;oid=121326447&amp;loc=d3e1500-109256<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 45<br> -Paragraph 23<br> -Subparagraph (c)<br> -URI http://asc.fasb.org/extlink&amp;oid=121326447&amp;loc=d3e1757-109256<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_IncrementalCommonSharesAttributableToShareBasedPaymentArrangements</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:sharesItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_NetIncomeLoss">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section 45<br> -Paragraph 1A<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=121641772&amp;loc=SL7669619-108580<br><br>Reference 2: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 31<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e8924-108599<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 250<br> -SubTopic 10<br> -Section 50<br> -Paragraph 11<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=109234566&amp;loc=d3e22694-107794<br><br>Reference 4: 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<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_NetIncomeLoss</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_NetIncomeLossAvailableToCommonStockholdersBasic">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount, after deduction of tax, noncontrolling interests, dividends on preferred stock and participating securities; of income (loss) available to common shareholders.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 250<br> -SubTopic 10<br> -Section 50<br> -Paragraph 4<br> -URI http://asc.fasb.org/extlink&amp;oid=109234566&amp;loc=d3e22595-107794<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 45<br> -Paragraph 10<br> -URI http://asc.fasb.org/extlink&amp;oid=121326447&amp;loc=d3e1448-109256<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 250<br> -SubTopic 10<br> -Section 50<br> -Paragraph 11<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=109234566&amp;loc=d3e22694-107794<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 45<br> -Paragraph 11<br> -URI http://asc.fasb.org/extlink&amp;oid=121326447&amp;loc=d3e1377-109256<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=6371337&amp;loc=d3e3550-109257<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 22<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e8736-108599<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 250<br> -SubTopic 10<br> -Section 50<br> -Paragraph 11<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=109234566&amp;loc=d3e22694-107794<br><br>Reference 8: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 45<br> -Paragraph 60B<br> -Subparagraph (c)<br> -URI http://asc.fasb.org/extlink&amp;oid=121326447&amp;loc=SL5780133-109256<br><br>Reference 9: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (f)<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e8933-108599<br><br>Reference 10: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 31<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e8924-108599<br><br>Reference 11: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 30<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e8906-108599<br><br>Reference 12: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 250<br> -SubTopic 10<br> -Section 50<br> -Paragraph 3<br> -URI http://asc.fasb.org/extlink&amp;oid=109234566&amp;loc=d3e22583-107794<br><br>Reference 13: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (c)<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e8933-108599<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_NetIncomeLossAvailableToCommonStockholdersBasic</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_NetIncomeLossAvailableToCommonStockholdersDiluted">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount, after deduction of tax, noncontrolling interests, dividends on preferred stock and participating securities, and addition from assumption of issuance of common shares for dilutive potential common shares; of income (loss) available to common shareholders.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 45<br> -Paragraph 60B<br> -Subparagraph (c)<br> -URI http://asc.fasb.org/extlink&amp;oid=121326447&amp;loc=SL5780133-109256<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=6371337&amp;loc=d3e3550-109257<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 45<br> -Paragraph 16<br> -URI http://asc.fasb.org/extlink&amp;oid=121326447&amp;loc=d3e1505-109256<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_NetIncomeLossAvailableToCommonStockholdersDiluted</td>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
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<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=6371337&amp;loc=d3e3550-109257<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 45<br> -Paragraph 16<br> -URI http://asc.fasb.org/extlink&amp;oid=121326447&amp;loc=d3e1505-109256<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>
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<td>us-gaap_</td>
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<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="top.Show.hideAR();">X</a></td></tr>
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<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=6371337&amp;loc=d3e3550-109257<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 45<br> -Paragraph 10<br> -URI http://asc.fasb.org/extlink&amp;oid=121326447&amp;loc=d3e1448-109256<br></p></div>
<a href="javascript:void(0);" onclick="top.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="top.Show.hideAR();">X</a></td></tr>
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<th class="th" colspan="4">1 Months Ended</th>
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<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerAbstract', window );"><strong>Revenue Recognition [Abstract]</strong></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="top.Show.showAR( this, 'defref_ions_RevenueFromContractWithCustomerNumberOfPerformanceObligationsAtInceptionOfContract', window );">Number of performance obligations at inception of contract | PerformanceObligation</a></td>
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<td class="text">&#160;<span></span>
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<td class="nump">1<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_NumberOfAgreementsWithCollaborationPartner', window );">Number of agreements | Agreement</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">2<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_srt_ProductOrServiceAxis=ions_LicensingAndOtherRoyaltiesMember', window );">Licensing and Other Royalties [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerAbstract', window );"><strong>Revenue Recognition [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">8,117<span></span>
</td>
<td class="nump">$ 17,205<span></span>
</td>
<td class="nump">$ 14,755<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="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJuly2015WithAstrazenecaMember', window );">AstraZeneca [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerAbstract', window );"><strong>Revenue Recognition [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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">$ 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>
<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="top.Show.showAR( this, 'defref_ions_UpfrontPaymentReceived', window );">Upfront payment received</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 65,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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="top.Show.showAR( this, 'defref_ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations', window );">Number of separate performance obligations | PerformanceObligation</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">1<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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="top.Show.showAR( this, 'defref_ions_RevenueFromContractWithCustomerTransactionPrice', window );">Transaction price</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 65,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJuly2015WithAstrazenecaMember', window );">AstraZeneca [Member] | ION455 [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>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerAbstract', window );"><strong>Revenue Recognition [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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">30,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="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="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember', window );">Roche IONIS-FB-L for Complement-Mediated Diseases [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerAbstract', window );"><strong>Revenue Recognition [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="num">(9,200)<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>
<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="top.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">$ 75,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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="top.Show.showAR( this, 'defref_ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations', window );">Number of separate performance obligations | PerformanceObligation</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">1<span></span>
</td>
<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="top.Show.showAR( this, 'defref_ions_RevenueFromContractWithCustomerTransactionPrice', window );">Transaction price</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 75,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember', window );">Biogen 2018 Strategic Neurology [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerAbstract', window );"><strong>Revenue Recognition [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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="top.Show.showAR( this, 'defref_ions_RevenueFromContractWithCustomerTransactionPriceAdditions', window );">Milestone payment received and added to 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">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>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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">$ 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>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations', window );">Number of separate performance obligations | PerformanceObligation</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="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="top.Show.showAR( this, 'defref_ions_RevenueFromContractWithCustomerTransactionPrice', window );">Transaction price</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 552,000<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember', window );">Biogen 2013 Strategic Neurology [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerAbstract', window );"><strong>Revenue Recognition [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 18,000<span></span>
</td>
<td class="num">$ (16,500)<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>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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">$ 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>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="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>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="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>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember', window );">Biogen 2013 Strategic Neurology [Member] | Licensing and Other Royalties [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerAbstract', window );"><strong>Revenue Recognition [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="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>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2004WithAlnylamPharmaceuticalsIncMember', window );">Alnylam [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerAbstract', window );"><strong>Revenue Recognition [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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">$ 41,200<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMay2015WithBayerMember', window );">Bayer [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>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerAbstract', window );"><strong>Revenue Recognition [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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="top.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">$ 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="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>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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">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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementAmendedInFebruary2017WithBayerMember', window );">Bayer [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>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerAbstract', window );"><strong>Revenue Recognition [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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="top.Show.showAR( this, 'defref_ions_UpfrontPaymentReceived', window );">Upfront payment received</a></td>
<td class="nump">$ 75,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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="top.Show.showAR( this, 'defref_ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations', window );">Number of separate performance obligations | PerformanceObligation</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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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="top.Show.showAR( this, 'defref_ions_RevenueFromContractWithCustomerTransactionPrice', window );">Transaction price</a></td>
<td class="nump">$ 75,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></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_NumberOfAgreementsWithCollaborationPartner">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The number of agreements entered into with the collaboration partner.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_NumberOfAgreementsWithCollaborationPartner</td>
</tr>
<tr>
<td style="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_RevenueFromContractWithCustomerNumberOfPerformanceObligationsAtInceptionOfContract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The number of performance obligations at the inception of a contract.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_RevenueFromContractWithCustomerNumberOfPerformanceObligationsAtInceptionOfContract</td>
</tr>
<tr>
<td style="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_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</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_RevenueFromContractWithCustomerTransactionPriceAdditions">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The additional amount of consideration the Company earned under the collaboration agreement that is added to the transaction price.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_RevenueFromContractWithCustomerTransactionPriceAdditions</td>
</tr>
<tr>
<td style="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_UpfrontPaymentReceived">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</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_RevenueFromContractWithCustomerAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 30<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e8906-108599<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 40<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e9031-108599<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 41<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e9038-108599<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e8933-108599<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e8933-108599<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=121604090&amp;loc=SL49130543-203045<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 22<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e8736-108599<br><br>Reference 8: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 22<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e8736-108599<br><br>Reference 9: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 42<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e9054-108599<br><br>Reference 10: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 50<br> -Paragraph 5<br> -URI http://asc.fasb.org/extlink&amp;oid=121604090&amp;loc=SL49130545-203045<br><br>Reference 11: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 924<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 11.L)<br> -URI http://asc.fasb.org/extlink&amp;oid=6472922&amp;loc=d3e499488-122856<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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_MajorCustomersAxis=ions_BiogenIncMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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_BiogenIncMember</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_LicensingAndOtherRoyaltiesMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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_LicensingAndOtherRoyaltiesMember</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_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJuly2015WithAstrazenecaMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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><strong> Name:</strong></td>
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<tr>
<td><strong> Name:</strong></td>
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<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember</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="top.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_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2004WithAlnylamPharmaceuticalsIncMember</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<td style="white-space:nowrap;">us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMay2015WithBayerMember</td>
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<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementAmendedInFebruary2017WithBayerMember</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<DOCUMENT>
<TYPE>XML
<SEQUENCE>72
<FILENAME>R36.htm
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<TEXT>
<html>
<head>
<title></title>
<link rel="stylesheet" type="text/css" href="report.css">
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<span style="display: none;">v3.20.4</span><table class="report" border="0" cellspacing="2" id="idm140142731517304">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Organization and Significant Accounting Policies, Contracts Receivable (Details)<br></strong></div></th>
<th class="th" colspan="1">12 Months Ended</th>
</tr>
<tr><th class="th"><div>Dec. 31, 2020</div></th></tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ContractReceivablesAbstract', window );"><strong>Contracts Receivable [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="top.Show.showAR( this, 'defref_ions_PeriodAfterBillingWhenPaymentIsReceived', window );">Period of time after billing when payment is received</a></td>
<td class="text">3 months<span></span>
</td>
</tr>
</table>
<div style="display: none;">
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<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</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>
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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_ContractReceivablesAbstract">
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<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>
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<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
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<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</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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<DOCUMENT>
<TYPE>XML
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<DESCRIPTION>IDEA: XBRL DOCUMENT
<TEXT>
<html>
<head>
<title></title>
<link rel="stylesheet" type="text/css" href="report.css">
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<span style="display: none;">v3.20.4</span><table class="report" border="0" cellspacing="2" id="idm140142826848584">
<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, 2020</div></th>
<th class="th"><div>Dec. 31, 2019</div></th>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="top.Show.showAR( this, 'defref_us-gaap_ContractWithCustomerLiabilityRevenueRecognized', window );">Revenue recognized from amounts in beginning deferred revenue balance</a></td>
<td class="nump">$ 100.4<span></span>
</td>
<td class="nump">$ 159.5<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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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">
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<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 50<br> -Paragraph 8<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=121604090&amp;loc=SL49130549-203045<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>74
<FILENAME>R38.htm
<DESCRIPTION>IDEA: XBRL DOCUMENT
<TEXT>
<html>
<head>
<title></title>
<link rel="stylesheet" type="text/css" href="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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<span style="display: none;">v3.20.4</span><table class="report" border="0" cellspacing="2" id="idm140142736050824">
<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 Thousands</strong></div></th>
<th class="th" colspan="3">12 Months Ended</th>
</tr>
<tr>
<th class="th"><div>Dec. 31, 2020</div></th>
<th class="th"><div>Dec. 31, 2019</div></th>
<th class="th"><div>Dec. 31, 2018</div></th>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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 " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ResearchAndDevelopmentExpense', window );">Research and development expenses</a></td>
<td class="nump">$ 531,000<span></span>
</td>
<td class="nump">$ 461,500<span></span>
</td>
<td class="nump">$ 411,900<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_FiniteLivedIntangibleAssetsFutureAmortizationExpenseAbstract', window );"><strong>Estimated Amortization 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="top.Show.showAR( this, 'defref_us-gaap_ImpairmentOfIntangibleAssetsFinitelived', window );">Non-cash charges related to write-down</a></td>
<td class="nump">1,948<span></span>
</td>
<td class="nump">2,226<span></span>
</td>
<td class="nump">802<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_FiniteLivedIntangibleAssetsByMajorClassAxis=us-gaap_PatentsMember', window );">Patents [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="top.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="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ResearchAndDevelopmentExpense', window );">Research and development expenses</a></td>
<td class="nump">$ 4,100<span></span>
</td>
<td class="nump">4,200<span></span>
</td>
<td class="nump">2,600<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_FiniteLivedIntangibleAssetUsefulLife', window );">Estimated useful life</a></td>
<td class="text">10 years 3 months 18 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="top.Show.showAR( this, 'defref_us-gaap_FiniteLivedIntangibleAssetsGross', window );">Cost</a></td>
<td class="nump">$ 37,000<span></span>
</td>
<td class="nump">34,000<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="top.Show.showAR( this, 'defref_us-gaap_FiniteLivedIntangibleAssetsAccumulatedAmortization', window );">Accumulated amortization</a></td>
<td class="nump">9,100<span></span>
</td>
<td class="nump">8,300<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_FiniteLivedIntangibleAssetsFutureAmortizationExpenseAbstract', window );"><strong>Estimated Amortization 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="top.Show.showAR( this, 'defref_us-gaap_FiniteLivedIntangibleAssetsAmortizationExpenseNextTwelveMonths', window );">2021</a></td>
<td class="nump">2,100<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_FiniteLivedIntangibleAssetsAmortizationExpenseYearTwo', window );">2022</a></td>
<td class="nump">2,000<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="top.Show.showAR( this, 'defref_us-gaap_FiniteLivedIntangibleAssetsAmortizationExpenseYearThree', window );">2023</a></td>
<td class="nump">1,900<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="top.Show.showAR( this, 'defref_us-gaap_FiniteLivedIntangibleAssetsAmortizationExpenseYearFour', window );">2024</a></td>
<td class="nump">1,700<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="top.Show.showAR( this, 'defref_us-gaap_FiniteLivedIntangibleAssetsAmortizationExpenseYearFive', window );">2025</a></td>
<td class="nump">1,600<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ImpairmentOfIntangibleAssetsFinitelived', window );">Non-cash charges related to write-down</a></td>
<td class="nump">1,900<span></span>
</td>
<td class="nump">2,200<span></span>
</td>
<td class="nump">800<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementsAndLicensingAgreementsMember', window );">Collaborative 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>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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 " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ResearchAndDevelopmentExpense', window );">Research and development expenses</a></td>
<td class="nump">$ 49,800<span></span>
</td>
<td class="nump">$ 83,200<span></span>
</td>
<td class="nump">$ 58,700<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_FiniteLivedIntangibleAssetUsefulLife">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Useful life of finite-lived intangible assets, 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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_FiniteLivedIntangibleAssetUsefulLife</td>
</tr>
<tr>
<td style="padding-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_FiniteLivedIntangibleAssetsAccumulatedAmortization">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Accumulated amount of amortization of assets, excluding financial assets and goodwill, lacking physical substance with a finite life.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 350<br> -SubTopic 30<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (a)(1)<br> -URI http://asc.fasb.org/extlink&amp;oid=66006027&amp;loc=d3e16323-109275<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_FiniteLivedIntangibleAssetsAccumulatedAmortization</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>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_FiniteLivedIntangibleAssetsAmortizationExpenseNextTwelveMonths">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of amortization for assets, excluding financial assets and goodwill, lacking physical substance with finite life expected to be recognized 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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 350<br> -SubTopic 30<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (a)(3)<br> -URI http://asc.fasb.org/extlink&amp;oid=66006027&amp;loc=d3e16323-109275<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_FiniteLivedIntangibleAssetsAmortizationExpenseNextTwelveMonths</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>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_FiniteLivedIntangibleAssetsAmortizationExpenseYearFive">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of amortization for assets, excluding financial assets and goodwill, lacking physical substance with finite life expected to be recognized 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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 350<br> -SubTopic 30<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (a)(3)<br> -URI http://asc.fasb.org/extlink&amp;oid=66006027&amp;loc=d3e16323-109275<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_FiniteLivedIntangibleAssetsAmortizationExpenseYearFive</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>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_FiniteLivedIntangibleAssetsAmortizationExpenseYearFour">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of amortization for assets, excluding financial assets and goodwill, lacking physical substance with finite life expected to be recognized 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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 350<br> -SubTopic 30<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (a)(3)<br> -URI http://asc.fasb.org/extlink&amp;oid=66006027&amp;loc=d3e16323-109275<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_FiniteLivedIntangibleAssetsAmortizationExpenseYearFour</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>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_FiniteLivedIntangibleAssetsAmortizationExpenseYearThree">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of amortization for assets, excluding financial assets and goodwill, lacking physical substance with finite life expected to be recognized 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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 350<br> -SubTopic 30<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (a)(3)<br> -URI http://asc.fasb.org/extlink&amp;oid=66006027&amp;loc=d3e16323-109275<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_FiniteLivedIntangibleAssetsAmortizationExpenseYearThree</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>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_FiniteLivedIntangibleAssetsAmortizationExpenseYearTwo">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of amortization for assets, excluding financial assets and goodwill, lacking physical substance with finite life expected to be recognized 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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 350<br> -SubTopic 30<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (a)(3)<br> -URI http://asc.fasb.org/extlink&amp;oid=66006027&amp;loc=d3e16323-109275<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_FiniteLivedIntangibleAssetsAmortizationExpenseYearTwo</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>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_FiniteLivedIntangibleAssetsFutureAmortizationExpenseAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_FiniteLivedIntangibleAssetsFutureAmortizationExpenseAbstract</td>
</tr>
<tr>
<td style="padding-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_FiniteLivedIntangibleAssetsGross">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount before amortization of assets, excluding financial assets and goodwill, lacking physical substance with a finite life.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 928<br> -SubTopic 340<br> -Section 50<br> -Paragraph 1<br> -URI http://asc.fasb.org/extlink&amp;oid=6473545&amp;loc=d3e61844-108004<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 350<br> -SubTopic 30<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (a)(1)<br> -URI http://asc.fasb.org/extlink&amp;oid=66006027&amp;loc=d3e16323-109275<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_FiniteLivedIntangibleAssetsGross</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>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_ImpairmentOfIntangibleAssetsFinitelived">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=121586364&amp;loc=d3e3602-108585<br><br>Reference 2: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 350<br> -SubTopic 30<br> -Section 50<br> -Paragraph 3<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=66006027&amp;loc=d3e16373-109275<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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_ResearchAndDevelopmentExpense">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 985<br> -SubTopic 20<br> -Section 50<br> -Paragraph 1<br> -URI http://asc.fasb.org/extlink&amp;oid=6501960&amp;loc=d3e128462-111756<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 730<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -URI http://asc.fasb.org/extlink&amp;oid=6420194&amp;loc=d3e21568-108373<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>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_ResearchAndDevelopmentExpenseAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>
</tr>
<tr>
<td style="padding-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_FiniteLivedIntangibleAssetsByMajorClassAxis=us-gaap_PatentsMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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_FiniteLivedIntangibleAssetsByMajorClassAxis=us-gaap_PatentsMember</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_CollaborativeArrangementsAndLicensingAgreementsMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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_CollaborativeArrangementsAndLicensingAgreementsMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
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<html>
<head>
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<span style="display: none;">v3.20.4</span><table class="report" border="0" cellspacing="2" id="idm140142726558296">
<tr>
<th class="tl" colspan="1" rowspan="1"><div style="width: 200px;"><strong>Organization and Significant Accounting Policies, Accrued Liabilities (Details) - USD ($)<br> $ in Thousands</strong></div></th>
<th class="th"><div>Dec. 31, 2020</div></th>
<th class="th"><div>Dec. 31, 2019</div></th>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="top.Show.showAR( this, 'defref_ions_AccruedClinicalExpenses', window );">Clincial expenses</a></td>
<td class="nump">$ 39,477<span></span>
</td>
<td class="nump">$ 24,461<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_AccruedInLicensingFeesCurrent', window );">In-licensing expenses</a></td>
<td class="nump">8,264<span></span>
</td>
<td class="nump">10,289<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_AccruedCommercialExpensesCurrent', window );">Commercial expenses</a></td>
<td class="nump">11,559<span></span>
</td>
<td class="nump">6,020<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_OtherAccruedLiabilitiesCurrent', window );">Other miscellaneous expenses</a></td>
<td class="nump">30,861<span></span>
</td>
<td class="nump">25,999<span></span>
</td>
</tr>
<tr class="rou">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AccruedLiabilitiesCurrent', window );">Total accrued liabilities</a></td>
<td class="nump">$ 90,161<span></span>
</td>
<td class="nump">$ 66,769<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_AccruedClinicalExpenses">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Carrying value as of the balance sheet date of obligations incurred through that date and payable for clinical expenses. Used to reflect the current portion of the liabilities (due within one year or within the normal operating cycle if longer).</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_AccruedClinicalExpenses</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
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<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_AccruedCommercialExpensesCurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</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>
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<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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</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>
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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>
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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_AccruedLiabilitiesCurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02.20)<br> -URI http://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>
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<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
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<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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02.20)<br> -URI http://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section 45<br> -Paragraph 6<br> -URI http://asc.fasb.org/extlink&amp;oid=121566466&amp;loc=d3e6911-107765<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section 45<br> -Paragraph 9<br> -URI http://asc.fasb.org/extlink&amp;oid=121566466&amp;loc=d3e7018-107765<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section 45<br> -Paragraph 8<br> -URI http://asc.fasb.org/extlink&amp;oid=121566466&amp;loc=d3e6935-107765<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>
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<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
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<td><strong> Period Type:</strong></td>
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<html>
<head>
<title></title>
<link rel="stylesheet" type="text/css" href="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;">v3.20.4</span><table class="report" border="0" cellspacing="2" id="idm140142735586696">
<tr>
<th class="tl" colspan="1" rowspan="1"><div style="width: 200px;"><strong>Organization and Significant Accounting Policies, Noncontrolling Interest in Akcea Therapeutics, Inc. (Details) - Akcea [Member]<br></strong></div></th>
<th class="th"><div>Oct. 31, 2020</div></th>
<th class="th"><div>Sep. 30, 2020</div></th>
<th class="th"><div>Jun. 30, 2017</div></th>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ProceedsFromIssuanceOrSaleOfEquityAbstract', window );"><strong>Noncontrolling Interest in Akcea Therapeutics, Inc. [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_MinorityInterestOwnershipPercentageByParent', window );">Percentage ownership</a></td>
<td class="nump">100.00%<span></span>
</td>
<td class="nump">76.00%<span></span>
</td>
<td class="nump">100.00%<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_srt_OwnershipAxis=ions_AkceaTherapeuticsIncMember', window );">Minimum [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ProceedsFromIssuanceOrSaleOfEquityAbstract', window );"><strong>Noncontrolling Interest in Akcea Therapeutics, Inc. [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_MinorityInterestOwnershipPercentageByParent', window );">Percentage ownership</a></td>
<td class="nump">68.00%<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="top.Show.showAR( this, 'defref_srt_OwnershipAxis=ions_AkceaTherapeuticsIncMember', window );">Maximum [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ProceedsFromIssuanceOrSaleOfEquityAbstract', window );"><strong>Noncontrolling Interest in Akcea Therapeutics, Inc. [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_MinorityInterestOwnershipPercentageByParent', window );">Percentage ownership</a></td>
<td class="nump">77.00%<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_us-gaap_MinorityInterestOwnershipPercentageByParent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The parent entity's interest in net assets of the subsidiary, expressed as a percentage.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_MinorityInterestOwnershipPercentageByParent</td>
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<td>num:percentItemType</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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</div></td></tr>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ProceedsFromIssuanceOrSaleOfEquityAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ProceedsFromIssuanceOrSaleOfEquityAbstract</td>
</tr>
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<td>us-gaap_</td>
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<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_srt_OwnershipAxis=ions_AkceaTherapeuticsIncMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">srt_OwnershipAxis=ions_AkceaTherapeuticsIncMember</td>
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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>
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<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_RangeAxis=srt_MinimumMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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>
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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>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_srt_RangeAxis=srt_MaximumMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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>
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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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<td><strong> Period Type:</strong></td>
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<span style="display: none;">v3.20.4</span><table class="report" border="0" cellspacing="2" id="idm140142741437576">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Organization and Significant Accounting Policies, Cash, Cash Equivalents and Investments (Details)<br> $ in Thousands</strong></div></th>
<th class="th" colspan="2">3 Months Ended</th>
<th class="th" colspan="1">9 Months Ended</th>
<th class="th" colspan="3">12 Months Ended</th>
</tr>
<tr>
<th class="th">
<div>Dec. 31, 2020 </div>
<div>USD ($) </div>
<div>Company</div>
</th>
<th class="th">
<div>Jun. 30, 2020 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Dec. 31, 2020 </div>
<div>Investment </div>
<div>Company</div>
</th>
<th class="th">
<div>Dec. 31, 2020 </div>
<div>USD ($) </div>
<div>Company</div>
</th>
<th class="th">
<div>Dec. 31, 2019 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Dec. 31, 2018 </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="top.Show.showAR( this, 'defref_us-gaap_CashCashEquivalentsAndShortTermInvestmentsAbstract', window );"><strong>Cash, Cash Equivalents and Investments [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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="top.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="nump">2<span></span>
</td>
<td class="text">&#160;<span></span>
</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="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="nump">7<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">7<span></span>
</td>
<td class="nump">7<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="top.Show.showAR( this, 'defref_ions_NumberOfInvestmentsInPrivatelyHeldCompaniesThatWereRevalued', window );">Number of investments in privately held companies that were revalued | Investment</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</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>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_GainLossOnInvestments', window );">Gain on investment</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 16,540<span></span>
</td>
<td class="nump">$ 192<span></span>
</td>
<td class="num">$ (210)<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_FinancialInstrumentAxis=ions_DynacureSasMember', window );">Dynacure SAS [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="top.Show.showAR( this, 'defref_us-gaap_CashCashEquivalentsAndShortTermInvestmentsAbstract', window );"><strong>Cash, Cash Equivalents and Investments [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_GainLossOnInvestments', window );">Gain on investment</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 6,300<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_FinancialInstrumentAxis=ions_SuzhouRiboLifeScienceCoLtdMember', window );">Suzhou-Ribo [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="top.Show.showAR( this, 'defref_us-gaap_CashCashEquivalentsAndShortTermInvestmentsAbstract', window );"><strong>Cash, Cash Equivalents and Investments [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_GainLossOnInvestments', window );">Gain on investment</a></td>
<td class="nump">$ 3,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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="top.Show.showAR( this, 'defref_us-gaap_FinancialInstrumentAxis=ions_AroBiotherapeuticsMember', window );">Aro Biotherapeutics [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="top.Show.showAR( this, 'defref_us-gaap_CashCashEquivalentsAndShortTermInvestmentsAbstract', window );"><strong>Cash, Cash Equivalents and Investments [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_GainLossOnInvestments', window );">Gain on investment</a></td>
<td class="nump">$ 5,500<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_NumberOfInvestmentsInPrivatelyHeldCompaniesThatWereRevalued">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Number of investments in privately-held companies that were revalued since the companies sold additional equity securities.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_NumberOfInvestmentsInPrivatelyHeldCompaniesThatWereRevalued</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
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<td><strong> Data Type:</strong></td>
<td>xbrli:integerItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
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<td>duration</td>
</tr>
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<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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</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>
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<td><strong> Period Type:</strong></td>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_CashCashEquivalentsAndShortTermInvestmentsAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_CashCashEquivalentsAndShortTermInvestmentsAbstract</td>
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<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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of realized and unrealized gain (loss) on investment.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 320<br> -SubTopic 10<br> -Section 50<br> -Paragraph 10<br> -Subparagraph (c)<br> -URI http://asc.fasb.org/extlink&amp;oid=121645371&amp;loc=d3e27405-111563<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.5-03.7(c),9(a))<br> -URI http://asc.fasb.org/extlink&amp;oid=120395209&amp;loc=SL114868664-224227<br><br>Reference 3: http://www.xbrl.org/2003/role/recommendedDisclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=121586364&amp;loc=d3e3602-108585<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>
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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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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_FinancialInstrumentAxis=ions_DynacureSasMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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_DynacureSasMember</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>na</td>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_FinancialInstrumentAxis=ions_SuzhouRiboLifeScienceCoLtdMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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_SuzhouRiboLifeScienceCoLtdMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
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<td><strong> Data Type:</strong></td>
<td>na</td>
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<td><strong> Balance Type:</strong></td>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_FinancialInstrumentAxis=ions_AroBiotherapeuticsMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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_AroBiotherapeuticsMember</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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<span style="display: none;">v3.20.4</span><table class="report" border="0" cellspacing="2" id="idm140142734582456">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Organization and Significant Accounting Policies, Inventory Valuation (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, 2020</div></th>
<th class="th"><div>Dec. 31, 2019</div></th>
<th class="th"><div>Dec. 31, 2018</div></th>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_InventoryNetAbstract', window );"><strong>Inventory Valuation [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="top.Show.showAR( this, 'defref_us-gaap_InventoryWriteDown', window );">Inventory write-off</a></td>
<td class="text"> <span></span>
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<td class="nump">$ 0<span></span>
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<tr class="re">
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<td class="nump">16,708<span></span>
</td>
<td class="nump">15,883<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_InventoryWorkInProcess', window );">Work in process</a></td>
<td class="nump">2,252<span></span>
</td>
<td class="nump">2,039<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="top.Show.showAR( this, 'defref_us-gaap_InventoryFinishedGoods', window );">Finished goods</a></td>
<td class="nump">3,005<span></span>
</td>
<td class="nump">258<span></span>
</td>
<td class="text">&#160;<span></span>
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</tr>
<tr class="rou">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_InventoryNet', window );">Total inventory</a></td>
<td class="nump">21,965<span></span>
</td>
<td class="nump">18,180<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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>
<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="top.Show.showAR( this, 'defref_us-gaap_InventoryNetAbstract', window );"><strong>Inventory Valuation [Abstract]</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="top.Show.showAR( this, 'defref_us-gaap_InventoryRawMaterials', window );">Raw materials</a></td>
<td class="nump">9,206<span></span>
</td>
<td class="nump">9,363<span></span>
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<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="top.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>
<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="top.Show.showAR( this, 'defref_us-gaap_InventoryNetAbstract', window );"><strong>Inventory Valuation [Abstract]</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="top.Show.showAR( this, 'defref_us-gaap_InventoryRawMaterials', window );">Raw materials</a></td>
<td class="nump">$ 7,502<span></span>
</td>
<td class="nump">$ 6,520<span></span>
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<td class="text">&#160;<span></span>
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<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_InventoryFinishedGoods">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02.6(a)(1))<br> -URI http://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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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<tr>
<td style="padding-right: 4px;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>
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<td>instant</td>
</tr>
</table></div>
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<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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section 45<br> -Paragraph 1<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=121566466&amp;loc=d3e6676-107765<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02.6(a))<br> -URI http://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>
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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>
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<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
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<td>instant</td>
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<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_InventoryNetAbstract</td>
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<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02.6(a)(4))<br> -URI http://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_InventoryRawMaterials</td>
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<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02.6(a)(3))<br> -URI http://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_InventoryWorkInProcess</td>
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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>
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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_InventoryWriteDown">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of loss from reductions in inventory due to subsequent measurement adjustments, including, but not limited to, physical deterioration, obsolescence, or changes in price levels.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 330<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -URI http://asc.fasb.org/extlink&amp;oid=116847112&amp;loc=d3e4542-108314<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_InventoryWriteDown</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>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_PublicUtilitiesInventoryAxis=ions_ClinicalRawMaterialsMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PublicUtilitiesInventoryAxis=ions_ClinicalRawMaterialsMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_PublicUtilitiesInventoryAxis=ions_CommercialRawMaterialsMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PublicUtilitiesInventoryAxis=ions_CommercialRawMaterialsMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
</div>
</body>
</html>
</TEXT>
</DOCUMENT>
<DOCUMENT>
<TYPE>XML
<SEQUENCE>79
<FILENAME>R43.htm
<DESCRIPTION>IDEA: XBRL DOCUMENT
<TEXT>
<html>
<head>
<title></title>
<link rel="stylesheet" type="text/css" href="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;">v3.20.4</span><table class="report" border="0" cellspacing="2" id="idm140142736331528">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Organization and Significant Accounting Policies, Property, Plant and Equipment (Details) - USD ($)<br> $ in Thousands</strong></div></th>
<th class="th" colspan="1">12 Months Ended</th>
<th class="th" colspan="1"></th>
</tr>
<tr>
<th class="th"><div>Dec. 31, 2020</div></th>
<th class="th"><div>Dec. 31, 2019</div></th>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="top.Show.showAR( this, 'defref_us-gaap_AccumulatedDepreciationDepletionAndAmortizationPropertyPlantAndEquipment', window );">Less accumulated depreciation</a></td>
<td class="num">$ (87,379)<span></span>
</td>
<td class="num">$ (74,013)<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentNet', window );">Property, plant and equipment, net</a></td>
<td class="nump">181,077<span></span>
</td>
<td class="nump">153,651<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="top.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="top.Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentGross', window );">Property, plant and equipment</a></td>
<td class="nump">245,394<span></span>
</td>
<td class="nump">204,602<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentNet', window );">Property, plant and equipment, net</a></td>
<td class="nump">158,015<span></span>
</td>
<td class="nump">130,589<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="top.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="top.Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentGross', window );">Property, plant and equipment</a></td>
<td class="nump">$ 68,990<span></span>
</td>
<td class="nump">60,965<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentByTypeAxis=ions_EquipmentAndComputerSoftwareMember', window );">Computer Software, Laboratory, Manufacturing and Other Equipment [Member] | Minimum [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="top.Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentUsefulLife', window );">Estimated useful lives</a></td>
<td class="text">3 years<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentByTypeAxis=ions_EquipmentAndComputerSoftwareMember', window );">Computer Software, Laboratory, Manufacturing and Other Equipment [Member] | Maximum [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="top.Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentUsefulLife', window );">Estimated useful lives</a></td>
<td class="text">10 years<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="top.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="top.Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentGross', window );">Property, plant and equipment</a></td>
<td class="nump">$ 137,879<span></span>
</td>
<td class="nump">119,830<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentByTypeAxis=us-gaap_BuildingAndBuildingImprovementsMember', window );">Building, Building Improvements and Building Systems [Member] | Minimum [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="top.Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentUsefulLife', window );">Estimated useful lives</a></td>
<td class="text">15 years<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentByTypeAxis=us-gaap_BuildingAndBuildingImprovementsMember', window );">Building, Building Improvements and Building Systems [Member] | Maximum [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="top.Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentUsefulLife', window );">Estimated useful lives</a></td>
<td class="text">40 years<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentByTypeAxis=us-gaap_LandImprovementsMember', window );">Land Improvements [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="top.Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentGross', window );">Property, plant and equipment</a></td>
<td class="nump">$ 8,391<span></span>
</td>
<td class="nump">2,853<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentUsefulLife', window );">Estimated useful lives</a></td>
<td class="text">20 years<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="top.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="top.Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentGross', window );">Property, plant and equipment</a></td>
<td class="nump">$ 17,263<span></span>
</td>
<td class="nump">13,600<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentByTypeAxis=us-gaap_LeaseholdImprovementsMember', window );">Leasehold Improvements [Member] | Minimum [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="top.Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentUsefulLife', window );">Estimated useful lives</a></td>
<td class="text">5 years<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentByTypeAxis=us-gaap_LeaseholdImprovementsMember', window );">Leasehold Improvements [Member] | Maximum [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="top.Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentUsefulLife', window );">Estimated useful lives</a></td>
<td class="text">15 years<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="top.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="top.Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentGross', window );">Property, plant and equipment</a></td>
<td class="nump">$ 12,871<span></span>
</td>
<td class="nump">7,354<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentByTypeAxis=us-gaap_FurnitureAndFixturesMember', window );">Furniture and Fixtures [Member] | Minimum [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="top.Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentUsefulLife', window );">Estimated useful lives</a></td>
<td class="text">5 years<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentByTypeAxis=us-gaap_FurnitureAndFixturesMember', window );">Furniture and Fixtures [Member] | Maximum [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="top.Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentUsefulLife', window );">Estimated useful lives</a></td>
<td class="text">10 years<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="top.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="top.Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentGross', window );">Property, plant and equipment</a></td>
<td class="nump">$ 23,062<span></span>
</td>
<td class="nump">$ 23,062<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_AccumulatedDepreciationDepletionAndAmortizationPropertyPlantAndEquipment">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 360<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (c)<br> -URI http://asc.fasb.org/extlink&amp;oid=6391035&amp;loc=d3e2868-110229<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02.14)<br> -URI http://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AccumulatedDepreciationDepletionAndAmortizationPropertyPlantAndEquipment</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
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<tr>
<td><strong> Data Type:</strong></td>
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</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_PropertyPlantAndEquipmentAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>
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</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
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<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_PropertyPlantAndEquipmentGross">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 360<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=6391035&amp;loc=d3e2868-110229<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02.13)<br> -URI http://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PropertyPlantAndEquipmentGross</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_PropertyPlantAndEquipmentNet">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(14))<br> -URI http://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 360<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -URI http://asc.fasb.org/extlink&amp;oid=6391035&amp;loc=d3e2868-110229<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 944<br> -SubTopic 210<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-03(a)(8))<br> -URI http://asc.fasb.org/extlink&amp;oid=120400017&amp;loc=d3e572229-122910<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(13))<br> -URI http://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PropertyPlantAndEquipmentNet</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_PropertyPlantAndEquipmentUsefulLife">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PropertyPlantAndEquipmentUsefulLife</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:durationItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_PropertyPlantAndEquipmentByTypeAxis=ions_PropertyPlantAndEquipmentExcludingLandMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PropertyPlantAndEquipmentByTypeAxis=ions_PropertyPlantAndEquipmentExcludingLandMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_PropertyPlantAndEquipmentByTypeAxis=ions_EquipmentAndComputerSoftwareMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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>
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</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_RangeAxis=srt_MaximumMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">srt_RangeAxis=srt_MaximumMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_PropertyPlantAndEquipmentByTypeAxis=us-gaap_BuildingAndBuildingImprovementsMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PropertyPlantAndEquipmentByTypeAxis=us-gaap_LandImprovementsMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_PropertyPlantAndEquipmentByTypeAxis=us-gaap_LeaseholdImprovementsMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PropertyPlantAndEquipmentByTypeAxis=us-gaap_LandMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
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<span style="display: none;">v3.20.4</span><table class="report" border="0" cellspacing="2" id="idm140142735724840">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Organization and Significant Accounting Policies, Long-Lived Assets (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, 2020</div></th>
<th class="th"><div>Dec. 31, 2019</div></th>
<th class="th"><div>Dec. 31, 2018</div></th>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AssetImpairmentChargesAbstract', window );"><strong>Long-Lived Assets [Abstract]</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="top.Show.showAR( this, 'defref_us-gaap_ImpairmentOfIntangibleAssetsFinitelived', window );">Charges related to write-down of patents</a></td>
<td class="nump">$ 1,948<span></span>
</td>
<td class="nump">$ 2,226<span></span>
</td>
<td class="nump">$ 802<span></span>
</td>
</tr>
</table>
<div style="display: none;">
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<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AssetImpairmentChargesAbstract</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<td><strong> Data Type:</strong></td>
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<td><strong> Period Type:</strong></td>
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<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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=121586364&amp;loc=d3e3602-108585<br><br>Reference 2: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 350<br> -SubTopic 30<br> -Section 50<br> -Paragraph 3<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=66006027&amp;loc=d3e16373-109275<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>
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<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
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<td><strong> Balance Type:</strong></td>
<td>debit</td>
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<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
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</table></div>
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<span style="display: none;">v3.20.4</span><table class="report" border="0" cellspacing="2" id="idm140142741571944">
<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, 2020</div></th></tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AwardTypeAxis=us-gaap_RestrictedStockUnitsRSUMember', window );">RSUs [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
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<td class="text">&#160;<span></span>
</td>
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<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1', window );">Vesting period</a></td>
<td class="text">4 years<span></span>
</td>
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</table>
<div style="display: none;">
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<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>
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<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (a)(1)<br> -URI http://asc.fasb.org/extlink&amp;oid=120381028&amp;loc=d3e5070-113901<br></p></div>
<a href="javascript:void(0);" onclick="top.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_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1</td>
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<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
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<html>
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<span style="display: none;">v3.20.4</span><table class="report" border="0" cellspacing="2" id="idm140142741074616">
<tr>
<th class="tl" colspan="2" rowspan="2"><div style="width: 200px;"><strong>Organization and Significant Accounting Policies, Accumulated Other Comprehensive Loss (Details) - USD ($)<br> $ in Thousands</strong></div></th>
<th class="th" colspan="3">12 Months Ended</th>
</tr>
<tr>
<th class="th"><div>Dec. 31, 2020</div></th>
<th class="th"><div>Dec. 31, 2019</div></th>
<th class="th"><div>Dec. 31, 2018</div></th>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ReclassificationFromAccumulatedOtherComprehensiveIncomeCurrentPeriodNetOfTaxAbstract', window );"><strong>Accumulated Other Comprehensive Loss [Roll Forward]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest', window );">Balance</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">$ 1,684,547<span></span>
</td>
<td class="nump">$ 1,187,160<span></span>
</td>
<td class="nump">$ 365,280<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_OtherComprehensiveIncomeLossAdjustmentsFromPurchaseOfNoncontrollingInterestOfSubsidiary', window );">Adjustments to other comprehensive loss from purchase of noncontrolling interest of Akcea Therapeutics, Inc.</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="num">(127)<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="top.Show.showAR( this, 'defref_us-gaap_OtherComprehensiveIncomeLossNetOfTax', window );">Net other comprehensive loss for the period</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">4,219<span></span>
</td>
<td class="nump">6,726<span></span>
</td>
<td class="num">(257)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest', window );">Balance</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">843,347<span></span>
</td>
<td class="nump">1,684,547<span></span>
</td>
<td class="nump">1,187,160<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_OtherComprehensiveIncomeLossTax', window );">Income tax expense (benefit) included in other comprehensive loss</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">0<span></span>
</td>
<td class="num">(1,400)<span></span>
</td>
<td class="num">(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="top.Show.showAR( this, 'defref_us-gaap_StatementEquityComponentsAxis=us-gaap_AociIncludingPortionAttributableToNoncontrollingInterestMember', window );">Accumulated Other Comprehensive Loss [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ReclassificationFromAccumulatedOtherComprehensiveIncomeCurrentPeriodNetOfTaxAbstract', window );"><strong>Accumulated Other Comprehensive Loss [Roll Forward]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest', window );">Balance</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="num">(25,290)<span></span>
</td>
<td class="num">(32,016)<span></span>
</td>
<td class="num">(31,759)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest', window );">Balance</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="num">(21,071)<span></span>
</td>
<td class="num">(25,290)<span></span>
</td>
<td class="num">(32,016)<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_StatementEquityComponentsAxis=us-gaap_AccumulatedNetInvestmentGainLossIncludingPortionAttributableToNoncontrollingInterestMember', window );">Unrealized Gains (Losses) on Securities [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ReclassificationFromAccumulatedOtherComprehensiveIncomeCurrentPeriodNetOfTaxAbstract', window );"><strong>Accumulated Other Comprehensive Loss [Roll Forward]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_OtherComprehensiveIncomeLossBeforeReclassificationsNetOfTax', window );">Other comprehensive loss before reclassifications, net of tax</a></td>
<td class="th" style="border-bottom: 0px;"><sup>[1]</sup></td>
<td class="nump">3,729<span></span>
</td>
<td class="nump">6,633<span></span>
</td>
<td class="num">(280)<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_StatementEquityComponentsAxis=us-gaap_AccumulatedForeignCurrencyAdjustmentIncludingPortionAttributableToNoncontrollingInterestMember', window );">Currency Translation Adjustment [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ReclassificationFromAccumulatedOtherComprehensiveIncomeCurrentPeriodNetOfTaxAbstract', window );"><strong>Accumulated Other Comprehensive Loss [Roll Forward]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_OtherComprehensiveIncomeLossBeforeReclassificationsNetOfTax', window );">Other comprehensive loss before reclassifications, net of tax</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">$ 617<span></span>
</td>
<td class="nump">$ 93<span></span>
</td>
<td class="nump">$ 23<span></span>
</td>
</tr>
<tr><td colspan="4"></td></tr>
<tr><td colspan="4"><table class="outerFootnotes" width="100%"><tr class="outerFootnote">
<td style="vertical-align: top; width: 12pt;" valign="top">[1]</td>
<td style="vertical-align: top;" valign="top">We did not have tax expense included in our other comprehensive loss for the year ended December 31, 2020. For the years ended December 31, 2019 and 2018, we had a tax benefit $1.4 million and $0.3 million included in other comprehensive loss respectively.</td>
</tr></table></td></tr>
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<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Adjustments to other comprehensive income (loss) from purchase of noncontrolling interest of subsidiary.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_OtherComprehensiveIncomeLossAdjustmentsFromPurchaseOfNoncontrollingInterestOfSubsidiary</td>
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<td><strong> Data Type:</strong></td>
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<td><strong> Balance Type:</strong></td>
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<td>duration</td>
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</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_OtherComprehensiveIncomeLossBeforeReclassificationsNetOfTax">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount after tax, before reclassification adjustments of other comprehensive income (loss).</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 830<br> -SubTopic 30<br> -Section 45<br> -Paragraph 17<br> -URI http://asc.fasb.org/extlink&amp;oid=118261656&amp;loc=d3e32136-110900<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 830<br> -SubTopic 30<br> -Section 50<br> -Paragraph 1<br> -URI http://asc.fasb.org/extlink&amp;oid=6450520&amp;loc=d3e32583-110901<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section 45<br> -Paragraph 14A<br> -URI http://asc.fasb.org/extlink&amp;oid=121641772&amp;loc=SL7669686-108580<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section 55<br> -Paragraph 15<br> -URI http://asc.fasb.org/extlink&amp;oid=121640130&amp;loc=d3e1436-108581<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 830<br> -SubTopic 30<br> -Section 45<br> -Paragraph 20<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=118261656&amp;loc=d3e32211-110900<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_OtherComprehensiveIncomeLossBeforeReclassificationsNetOfTax</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
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</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_OtherComprehensiveIncomeLossNetOfTax">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount after tax and reclassification adjustments of other comprehensive income (loss).</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section 45<br> -Paragraph 1A<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=121641772&amp;loc=SL7669619-108580<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 505<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -URI http://asc.fasb.org/extlink&amp;oid=109259400&amp;loc=d3e21463-112644<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 830<br> -SubTopic 30<br> -Section 45<br> -Paragraph 17<br> -URI http://asc.fasb.org/extlink&amp;oid=118261656&amp;loc=d3e32136-110900<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.5-03(21))<br> -URI http://asc.fasb.org/extlink&amp;oid=120395209&amp;loc=SL114868664-224227<br><br>Reference 5: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section 55<br> -Paragraph 15<br> -URI http://asc.fasb.org/extlink&amp;oid=121640130&amp;loc=d3e1436-108581<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 830<br> -SubTopic 30<br> -Section 45<br> -Paragraph 20<br> -URI http://asc.fasb.org/extlink&amp;oid=118261656&amp;loc=d3e32211-110900<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 830<br> -SubTopic 30<br> -Section 50<br> -Paragraph 1<br> -URI http://asc.fasb.org/extlink&amp;oid=6450520&amp;loc=d3e32583-110901<br><br>Reference 8: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section 45<br> -Paragraph 1B<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=121641772&amp;loc=SL7669625-108580<br><br>Reference 9: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 942<br> -SubTopic 220<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-04(23))<br> -URI http://asc.fasb.org/extlink&amp;oid=120399700&amp;loc=SL114874048-224260<br><br>Reference 10: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 944<br> -SubTopic 220<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-04(19))<br> -URI http://asc.fasb.org/extlink&amp;oid=120400993&amp;loc=SL114874131-224263<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_OtherComprehensiveIncomeLossNetOfTax</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<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_OtherComprehensiveIncomeLossTax">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of tax expense (benefit) allocated to other comprehensive income (loss).</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 20<br> -Section 45<br> -Paragraph 11<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=120385591&amp;loc=d3e39076-109324<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 830<br> -SubTopic 30<br> -Section 45<br> -Paragraph 17<br> -URI http://asc.fasb.org/extlink&amp;oid=118261656&amp;loc=d3e32136-110900<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 830<br> -SubTopic 30<br> -Section 45<br> -Paragraph 20<br> -Subparagraph (c)<br> -URI http://asc.fasb.org/extlink&amp;oid=118261656&amp;loc=d3e32211-110900<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 20<br> -Section 45<br> -Paragraph 2<br> -Subparagraph (d)<br> -URI http://asc.fasb.org/extlink&amp;oid=120385591&amp;loc=d3e38679-109324<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 942<br> -SubTopic 220<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-04(23))<br> -URI http://asc.fasb.org/extlink&amp;oid=120399700&amp;loc=SL114874048-224260<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.5-03(21))<br> -URI http://asc.fasb.org/extlink&amp;oid=120395209&amp;loc=SL114868664-224227<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 10<br> -URI http://asc.fasb.org/extlink&amp;oid=84230637&amp;loc=d3e32672-109319<br><br>Reference 8: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 830<br> -SubTopic 30<br> -Section 50<br> -Paragraph 1<br> -URI http://asc.fasb.org/extlink&amp;oid=6450520&amp;loc=d3e32583-110901<br><br>Reference 9: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section 45<br> -Paragraph 12<br> -URI http://asc.fasb.org/extlink&amp;oid=121641772&amp;loc=d3e640-108580<br><br>Reference 10: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 944<br> -SubTopic 220<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-04(19))<br> -URI http://asc.fasb.org/extlink&amp;oid=120400993&amp;loc=SL114874131-224263<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_OtherComprehensiveIncomeLossTax</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>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_ReclassificationFromAccumulatedOtherComprehensiveIncomeCurrentPeriodNetOfTaxAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ReclassificationFromAccumulatedOtherComprehensiveIncomeCurrentPeriodNetOfTaxAbstract</td>
</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_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of stockholders' equity (deficit), net of receivables from officers, directors, owners, and affiliates of the entity, attributable to both the parent and noncontrolling interests. Amount excludes temporary equity. Alternate caption for the concept is permanent equity.</p></div>
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<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>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>
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<td><strong> Name:</strong></td>
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<head>
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<span style="display: none;">v3.20.4</span><table class="report" border="0" cellspacing="2" id="idm140142726578152">
<tr>
<th class="tl" colspan="1" rowspan="1"><div style="width: 200px;"><strong>Organization and Significant Accounting Policies, Convertible Debt (Details)<br></strong></div></th>
<th class="th"><div>Dec. 31, 2020</div></th>
<th class="th"><div>Dec. 31, 2019</div></th>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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">
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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="top.Show.showAR( this, 'defref_us-gaap_DebtInstrumentInterestRateStatedPercentage', window );">Interest rate on convertible senior notes</a></td>
<td class="nump">0.125%<span></span>
</td>
<td class="nump">0.125%<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_LongtermConvertibleDebtCurrentAndNoncurrentAbstract', window );"><strong>Convertible Debt [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="top.Show.showAR( this, 'defref_us-gaap_DebtInstrumentInterestRateStatedPercentage', window );">Interest rate on convertible senior notes</a></td>
<td class="nump">1.00%<span></span>
</td>
<td class="nump">1.00%<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02.22(a)(1))<br> -URI http://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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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<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.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="top.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_ConvertibleSeniorNotes1PercentMember</td>
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<TEXT>
<html>
<head>
<title></title>
<link rel="stylesheet" type="text/css" href="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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<body>
<span style="display: none;">v3.20.4</span><table class="report" border="0" cellspacing="2" id="idm140142735697976">
<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, 2020</div></th>
<th class="th"><div>Dec. 31, 2019</div></th>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="top.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>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_DebtInstrumentInterestRateStatedPercentage', window );">Interest rate on convertible senior notes</a></td>
<td class="nump">0.125%<span></span>
</td>
<td class="nump">0.125%<span></span>
</td>
</tr>
</table>
<div style="display: none;">
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<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02.22(a)(1))<br> -URI http://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.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="top.Show.hideAR();">X</a></td></tr>
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<a href="javascript:void(0);" onclick="top.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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<head>
<title></title>
<link rel="stylesheet" type="text/css" href="report.css">
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<span style="display: none;">v3.20.4</span><table class="report" border="0" cellspacing="2" id="idm140142726465592">
<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, 2020 </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="top.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="top.Show.showAR( this, 'defref_us-gaap_NumberOfOperatingSegments', window );">Number of operating segments</a></td>
<td class="nump">2<span></span>
</td>
</tr>
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<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 18<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e8672-108599<br></p></div>
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>
</tr>
<tr>
<td style="padding-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>86
<FILENAME>R50.htm
<DESCRIPTION>IDEA: XBRL DOCUMENT
<TEXT>
<html>
<head>
<title></title>
<link rel="stylesheet" type="text/css" href="report.css">
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<span style="display: none;">v3.20.4</span><table class="report" border="0" cellspacing="2" id="idm140142735257816">
<tr>
<th class="tl" colspan="2" rowspan="1"><div style="width: 200px;"><strong>Organization and Significant Accounting Policies, Fair Value Measurements (Details) - Recurring Basis [Member] - USD ($)<br> $ in Thousands</strong></div></th>
<th class="th" colspan="2"><div>Dec. 31, 2020</div></th>
<th class="th" colspan="2"><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="top.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>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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">$ 221,125<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">$ 418,406<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_EquitySecuritiesFvNi', window );">Investment in ProQR NV</a></td>
<td class="th" style="border-bottom: 0px;"><sup>[2]</sup></td>
<td class="nump">2,031<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">4,506<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="rou">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AssetsFairValueDisclosure', window );">Total</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">1,745,363<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">2,258,985<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_FairValueByMeasurementFrequencyAxis=us-gaap_FairValueMeasurementsRecurringMember', 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="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecurities', window );">Available-for-sale securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">846,315<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"><sup>[3]</sup></td>
<td class="nump">1,102,568<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"><sup>[4]</sup></td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_FairValueByMeasurementFrequencyAxis=us-gaap_FairValueMeasurementsRecurringMember', window );">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>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecurities', window );">Available-for-sale securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">10,000<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">19,000<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_FairValueByMeasurementFrequencyAxis=us-gaap_FairValueMeasurementsRecurringMember', 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="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecurities', window );">Available-for-sale securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">174,861<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"><sup>[5]</sup></td>
<td class="nump">329,404<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"><sup>[6]</sup></td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_FairValueByMeasurementFrequencyAxis=us-gaap_FairValueMeasurementsRecurringMember', window );">Debt Securities issued by U.S. Government Agencies [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>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecurities', 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">800<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_FairValueByMeasurementFrequencyAxis=us-gaap_FairValueMeasurementsRecurringMember', 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="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecurities', window );">Available-for-sale securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">358,497<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"><sup>[7]</sup></td>
<td class="nump">363,694<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"><sup>[5]</sup></td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_FairValueByMeasurementFrequencyAxis=us-gaap_FairValueMeasurementsRecurringMember', window );">Debt Securities issued by the U.S. Treasury [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>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecurities', window );">Available-for-sale securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">17,500<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>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_FairValueByMeasurementFrequencyAxis=us-gaap_FairValueMeasurementsRecurringMember', 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="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecurities', window );">Available-for-sale securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup>[5]</sup></td>
<td class="nump">136,309<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">40,407<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_FairValueByMeasurementFrequencyAxis=us-gaap_FairValueMeasurementsRecurringMember', 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="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecurities', window );">Available-for-sale securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup>[5]</sup></td>
<td class="nump">6,225<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>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_FairValueByMeasurementFrequencyAxis=us-gaap_FairValueMeasurementsRecurringMember', window );">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>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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">221,125<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">418,406<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_EquitySecuritiesFvNi', window );">Investment in ProQR NV</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">2,031<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>
</tr>
<tr class="reu">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AssetsFairValueDisclosure', window );">Total</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">581,653<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">782,100<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_FairValueByMeasurementFrequencyAxis=us-gaap_FairValueMeasurementsRecurringMember', window );">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>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecurities', 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>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_FairValueByMeasurementFrequencyAxis=us-gaap_FairValueMeasurementsRecurringMember', window );">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>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecurities', 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>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_FairValueByMeasurementFrequencyAxis=us-gaap_FairValueMeasurementsRecurringMember', window );">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>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecurities', window );">Available-for-sale securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">358,497<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">363,694<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_FairValueByMeasurementFrequencyAxis=us-gaap_FairValueMeasurementsRecurringMember', window );">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>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecurities', 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>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_FairValueByMeasurementFrequencyAxis=us-gaap_FairValueMeasurementsRecurringMember', window );">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>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecurities', 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="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_FairValueByMeasurementFrequencyAxis=us-gaap_FairValueMeasurementsRecurringMember', window );">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>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_EquitySecuritiesFvNi', window );">Investment in ProQR NV</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>
</tr>
<tr class="reu">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AssetsFairValueDisclosure', window );">Total</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">1,163,710<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">1,472,379<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_FairValueByMeasurementFrequencyAxis=us-gaap_FairValueMeasurementsRecurringMember', window );">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>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecurities', window );">Available-for-sale securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">846,315<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">1,102,568<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_FairValueByMeasurementFrequencyAxis=us-gaap_FairValueMeasurementsRecurringMember', window );">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>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecurities', window );">Available-for-sale securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">174,861<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">329,404<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_FairValueByMeasurementFrequencyAxis=us-gaap_FairValueMeasurementsRecurringMember', window );">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>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecurities', 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>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_FairValueByMeasurementFrequencyAxis=us-gaap_FairValueMeasurementsRecurringMember', window );">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>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecurities', window );">Available-for-sale securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">136,309<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">40,407<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_FairValueByMeasurementFrequencyAxis=us-gaap_FairValueMeasurementsRecurringMember', window );">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>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecurities', window );">Available-for-sale securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">$ 6,225<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>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_FairValueByMeasurementFrequencyAxis=us-gaap_FairValueMeasurementsRecurringMember', window );">Significant Unobservable Inputs (Level 3) [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_CashAndCashEquivalentsFairValueDisclosure', window );">Cash equivalents</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">0<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_EquitySecuritiesFvNi', window );">Investment in ProQR NV</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">4,506<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="reu">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AssetsFairValueDisclosure', window );">Total</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">4,506<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_FairValueByMeasurementFrequencyAxis=us-gaap_FairValueMeasurementsRecurringMember', window );">Significant Unobservable Inputs (Level 3) [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>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecurities', 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>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_FairValueByMeasurementFrequencyAxis=us-gaap_FairValueMeasurementsRecurringMember', window );">Significant Unobservable Inputs (Level 3) [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>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecurities', 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>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_FairValueByMeasurementFrequencyAxis=us-gaap_FairValueMeasurementsRecurringMember', window );">Significant Unobservable Inputs (Level 3) [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>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecurities', 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>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_FairValueByMeasurementFrequencyAxis=us-gaap_FairValueMeasurementsRecurringMember', window );">Significant Unobservable Inputs (Level 3) [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>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecurities', 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>
</tr>
<tr><td colspan="5"></td></tr>
<tr><td colspan="5"><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 on our consolidated balance sheet.</td>
</tr>
<tr class="outerFootnote">
<td style="vertical-align: top; width: 12pt;" valign="top">[2]</td>
<td style="vertical-align: top;" valign="top">Included in other current assets on our consolidated balance sheet.</td>
</tr>
<tr class="outerFootnote">
<td style="vertical-align: top; width: 12pt;" valign="top">[3]</td>
<td style="vertical-align: top;" valign="top">$10.0 million included in cash and cash equivalents on our consolidated balance sheet, with the difference included in short-term investments on our consolidated balance sheet.</td>
</tr>
<tr class="outerFootnote">
<td style="vertical-align: top; width: 12pt;" valign="top">[4]</td>
<td style="vertical-align: top;" valign="top">$19.0 million included in cash and cash equivalents on our consolidated balance sheet, with the difference included in short-term investments on our consolidated balance sheet.</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 short-term investments.</td>
</tr>
<tr class="outerFootnote">
<td style="vertical-align: top; width: 12pt;" valign="top">[6]</td>
<td style="vertical-align: top;" valign="top">$0.8 million included in cash and cash equivalents on our consolidated balance sheet, with the difference included in short-term investments on our consolidated balance sheet.</td>
</tr>
<tr class="outerFootnote">
<td style="vertical-align: top; width: 12pt;" valign="top">[7]</td>
<td style="vertical-align: top;" valign="top">$17.5 million included in cash and cash equivalents on our consolidated balance sheet, with the difference included in short-term investments on our consolidated balance sheet.</td>
</tr>
</table></td></tr>
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<div style="display: none;">
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<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 820<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=117815213&amp;loc=d3e19207-110258<br></p></div>
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of investment in debt and equity securities categorized neither as held-to-maturity nor trading.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.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="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.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="top.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).</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 825<br> -SubTopic 10<br> -Section 45<br> -Paragraph 1A<br> -URI http://asc.fasb.org/extlink&amp;oid=99377092&amp;loc=SL75136599-209740<br></p></div>
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
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<td><strong> Name:</strong></td>
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<td style="white-space:nowrap;">us-gaap_FairValueByFairValueHierarchyLevelAxis=us-gaap_FairValueInputsLevel1Member</td>
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<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></td>
</tr>
</table></div>
</div></td></tr>
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<tr>
<td><strong> Name:</strong></td>
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<tr>
<td><strong> Name:</strong></td>
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<DOCUMENT>
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<DESCRIPTION>IDEA: XBRL DOCUMENT
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<html>
<head>
<title></title>
<link rel="stylesheet" type="text/css" href="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;">v3.20.4</span><table class="report" border="0" cellspacing="2" id="idm140142732038728">
<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, 2020 </div>
<div>Company</div>
</th></tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="top.Show.showAR( this, 'defref_ions_AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage', window );">One year or less</a></td>
<td class="nump">73.00%<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="top.Show.showAR( this, 'defref_ions_AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage', window );">After one year but within two years</a></td>
<td class="nump">18.00%<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="top.Show.showAR( this, 'defref_ions_AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeAndOneHalfYearsPercentage', window );">After two years but within three and a half years</a></td>
<td class="nump">9.00%<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="top.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="top.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">91.00%<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="top.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="top.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="top.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>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_InvestmentsAllOtherInvestmentsAbstract', window );"><strong>Ownership Interests in Private and Public Companies [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="top.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>
<td class="nump">7<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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">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_AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</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>
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<td>num:percentItemType</td>
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<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeAndOneHalfYearsPercentage">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</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>
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<td><strong> Data Type:</strong></td>
<td>num:percentItemType</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_AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</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>num: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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</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>num:percentItemType</td>
</tr>
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<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_ions_AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</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>num: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_ions_MaximumContractMaturityPeriodRange1">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</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>
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<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_MaximumContractMaturityPeriodRange2">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</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>
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<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
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<td><strong> Data Type:</strong></td>
<td>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>
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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_ions_MaximumContractMaturityPeriodRange3">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</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_ions_NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</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>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AvailableForSaleSecuritiesDebtMaturitiesAbstract">
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<td style="white-space:nowrap;">us-gaap_AvailableForSaleSecuritiesDebtMaturitiesAbstract</td>
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<DOCUMENT>
<TYPE>XML
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<DESCRIPTION>IDEA: XBRL DOCUMENT
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<html>
<head>
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<span style="display: none;">v3.20.4</span><table class="report" border="0" cellspacing="2" id="idm140142740742248">
<tr>
<th class="tl" colspan="2" rowspan="2"><div style="width: 200px;"><strong>Investments, Summary of Investments (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, 2020</div></th>
<th class="th" colspan="2"><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="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract', window );"><strong>Summary of Investments [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>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="rou">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiCost', window );">Cost</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">$ 1,533,544<span></span>
</td>
<td class="nump">$ 1,846,074<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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">24,515<span></span>
</td>
<td class="nump">5,007<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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">(2,821)<span></span>
</td>
<td class="num">(1,166)<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="reu">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNi', window );">Estimated fair value</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">1,555,238<span></span>
</td>
<td class="nump">1,849,915<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_InvestmentTypeAxis=us-gaap_DebtSecuritiesMember', window );">Available-for-sale Securities [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract', window );"><strong>Summary of Investments [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>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="rou">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis', window );">Cost</a></td>
<td class="th" style="border-bottom: 0px;"><sup>[1]</sup></td>
<td class="nump">1,513,770<span></span>
</td>
<td class="nump">1,831,362<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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">8,577<span></span>
</td>
<td class="nump">5,007<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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">(140)<span></span>
</td>
<td class="num">(296)<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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">1,522,207<span></span>
</td>
<td class="nump">1,836,073<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_InvestmentTypeAxis=us-gaap_DebtSecuritiesMember', window );">Available-for-sale Securities [Member] | Securities with Maturity of One Year or Less [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract', window );"><strong>Summary of Investments [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>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="rou">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis', window );">Cost</a></td>
<td class="th" style="border-bottom: 0px;"><sup>[1]</sup></td>
<td class="nump">1,025,454<span></span>
</td>
<td class="nump">1,206,616<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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">2,977<span></span>
</td>
<td class="nump">2,012<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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">(71)<span></span>
</td>
<td class="num">(118)<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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">1,028,360<span></span>
</td>
<td class="nump">1,208,510<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_InvestmentTypeAxis=us-gaap_DebtSecuritiesMember', window );">Available-for-sale Securities [Member] | Securities with Maturity of More than One Year [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract', window );"><strong>Summary of Investments [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>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="rou">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis', window );">Cost</a></td>
<td class="th" style="border-bottom: 0px;"><sup>[1]</sup></td>
<td class="nump">488,316<span></span>
</td>
<td class="nump">624,746<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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">5,600<span></span>
</td>
<td class="nump">2,995<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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">(69)<span></span>
</td>
<td class="num">(178)<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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">493,847<span></span>
</td>
<td class="nump">627,563<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_InvestmentTypeAxis=us-gaap_CorporateDebtSecuritiesMember', window );">Corporate Debt Securities [Member] | Securities with Maturity of One Year or Less [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract', window );"><strong>Summary of Investments [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>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="rou">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis', window );">Cost</a></td>
<td class="th" style="border-bottom: 0px;"><sup>[1],[2]</sup></td>
<td class="nump">514,182<span></span>
</td>
<td class="nump">669,665<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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">2,194<span></span>
</td>
<td class="nump">1,451<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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">(41)<span></span>
</td>
<td class="num">(43)<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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">516,335<span></span>
</td>
<td class="nump">671,073<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_InvestmentTypeAxis=us-gaap_CorporateDebtSecuritiesMember', window );">Corporate Debt Securities [Member] | Securities with Maturity of More than One Year [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract', window );"><strong>Summary of Investments [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>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="rou">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis', window );">Cost</a></td>
<td class="th" style="border-bottom: 0px;"><sup>[1]</sup></td>
<td class="nump">325,079<span></span>
</td>
<td class="nump">428,627<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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">4,941<span></span>
</td>
<td class="nump">2,911<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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">(40)<span></span>
</td>
<td class="num">(43)<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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">329,980<span></span>
</td>
<td class="nump">431,495<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_InvestmentTypeAxis=us-gaap_USGovernmentAgenciesDebtSecuritiesMember', window );">Debt Securities issued by U.S. Government Agencies [Member] | Securities with Maturity of One Year or Less [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract', window );"><strong>Summary of Investments [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>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="rou">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis', window );">Cost</a></td>
<td class="th" style="border-bottom: 0px;"><sup>[1]</sup></td>
<td class="nump">94,234<span></span>
</td>
<td class="nump">188,216<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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">354<span></span>
</td>
<td class="nump">303<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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">(2)<span></span>
</td>
<td class="num">(43)<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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">94,586<span></span>
</td>
<td class="nump">188,476<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_InvestmentTypeAxis=us-gaap_USGovernmentAgenciesDebtSecuritiesMember', window );">Debt Securities issued by U.S. Government Agencies [Member] | Securities with Maturity of More than One Year [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract', window );"><strong>Summary of Investments [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>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="rou">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis', window );">Cost</a></td>
<td class="th" style="border-bottom: 0px;"><sup>[1]</sup></td>
<td class="nump">80,099<span></span>
</td>
<td class="nump">140,988<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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">185<span></span>
</td>
<td class="nump">57<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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">(9)<span></span>
</td>
<td class="num">(117)<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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">80,275<span></span>
</td>
<td class="nump">140,928<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_InvestmentTypeAxis=us-gaap_USTreasurySecuritiesMember', window );">Debt Securities issued by the U.S. Treasury [Member] | Securities with Maturity of One Year or Less [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract', window );"><strong>Summary of Investments [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>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="rou">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis', window );">Cost</a></td>
<td class="th" style="border-bottom: 0px;"><sup>[1],[2]</sup></td>
<td class="nump">307,576<span></span>
</td>
<td class="nump">327,670<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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">233<span></span>
</td>
<td class="nump">232<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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">(9)<span></span>
</td>
<td class="num">(27)<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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">307,800<span></span>
</td>
<td class="nump">327,875<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_InvestmentTypeAxis=us-gaap_USTreasurySecuritiesMember', window );">Debt Securities issued by the U.S. Treasury [Member] | Securities with Maturity of More than One Year [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract', window );"><strong>Summary of Investments [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>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="rou">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis', window );">Cost</a></td>
<td class="th" style="border-bottom: 0px;"><sup>[1]</sup></td>
<td class="nump">50,318<span></span>
</td>
<td class="nump">35,822<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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">383<span></span>
</td>
<td class="nump">9<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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">(4)<span></span>
</td>
<td class="num">(12)<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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">50,697<span></span>
</td>
<td class="nump">35,819<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_InvestmentTypeAxis=us-gaap_USStatesAndPoliticalSubdivisionsMember', window );">Debt Securities issued by States of the U.S. and Political Subdivisions of the States [Member] | Securities with Maturity of One Year or Less [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract', window );"><strong>Summary of Investments [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>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="rou">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis', window );">Cost</a></td>
<td class="th" style="border-bottom: 0px;"><sup>[1]</sup></td>
<td class="nump">104,271<span></span>
</td>
<td class="nump">21,065<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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">196<span></span>
</td>
<td class="nump">26<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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">(12)<span></span>
</td>
<td class="num">(5)<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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">104,455<span></span>
</td>
<td class="nump">21,086<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_InvestmentTypeAxis=us-gaap_USStatesAndPoliticalSubdivisionsMember', window );">Debt Securities issued by States of the U.S. and Political Subdivisions of the States [Member] | Securities with Maturity of More than One Year [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract', window );"><strong>Summary of Investments [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>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="rou">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis', window );">Cost</a></td>
<td class="th" style="border-bottom: 0px;"><sup>[1]</sup></td>
<td class="nump">31,779<span></span>
</td>
<td class="nump">19,309<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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">91<span></span>
</td>
<td class="nump">18<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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">(16)<span></span>
</td>
<td class="num">(6)<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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">31,854<span></span>
</td>
<td class="nump">19,321<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_InvestmentTypeAxis=us-gaap_OtherDebtSecuritiesMember', window );">Other Municipal Debt Securities [Member] | Securities with Maturity of One Year or Less [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract', window );"><strong>Summary of Investments [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>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="rou">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis', window );">Cost</a></td>
<td class="th" style="border-bottom: 0px;"><sup>[1]</sup></td>
<td class="nump">5,191<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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">0<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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">(7)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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">5,184<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_InvestmentTypeAxis=us-gaap_OtherDebtSecuritiesMember', window );">Other Municipal Debt Securities [Member] | Securities with Maturity of More than One Year [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract', window );"><strong>Summary of Investments [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>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="rou">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis', window );">Cost</a></td>
<td class="th" style="border-bottom: 0px;"><sup>[1]</sup></td>
<td class="nump">1,041<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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">0<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="nump">0<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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">1,041<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_InvestmentTypeAxis=us-gaap_EquitySecuritiesMember', window );">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>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract', window );"><strong>Summary of Investments [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>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_EquitySecuritiesFvNiCost', window );">Cost</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">19,774<span></span>
</td>
<td class="nump">14,712<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_EquitySecuritiesFvNiUnrealizedGain', window );">Gross unrealized gains</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">15,938<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_EquitySecuritiesFvNiUnrealizedLoss', window );">Gross unrealized losses</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="num">(2,681)<span></span>
</td>
<td class="num">(870)<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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">33,031<span></span>
</td>
<td class="nump">13,842<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_InvestmentTypeAxis=ions_EquitySecuritiesPubliclyTradedCompaniesMember', window );">Equity Securities in Publicly Traded Company [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract', window );"><strong>Summary of Investments [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>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_EquitySecuritiesFvNiCost', window );">Cost</a></td>
<td class="th" style="border-bottom: 0px;"><sup>[3]</sup></td>
<td class="nump">4,712<span></span>
</td>
<td class="nump">4,712<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_EquitySecuritiesFvNiUnrealizedGain', window );">Gross unrealized gains</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_EquitySecuritiesFvNiUnrealizedLoss', window );">Gross unrealized losses</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="num">(2,681)<span></span>
</td>
<td class="num">(870)<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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">2,031<span></span>
</td>
<td class="nump">3,842<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_InvestmentTypeAxis=ions_EquitySecuritiesPrivateCompaniesMember', window );">Equity Securities in Private Companies [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract', window );"><strong>Summary of Investments [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>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_EquitySecuritiesFvNiCost', window );">Cost</a></td>
<td class="th" style="border-bottom: 0px;"><sup>[4]</sup></td>
<td class="nump">15,062<span></span>
</td>
<td class="nump">10,000<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_EquitySecuritiesFvNiUnrealizedGain', window );">Gross unrealized gains</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">15,938<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"><sup>[4]</sup></td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_EquitySecuritiesFvNiUnrealizedLoss', window );">Gross unrealized losses</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"><sup>[4]</sup></td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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">$ 31,000<span></span>
</td>
<td class="nump">$ 10,000<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"><sup>[4]</sup></td>
</tr>
<tr><td colspan="4"></td></tr>
<tr><td colspan="4"><table class="outerFootnotes" width="100%">
<tr class="outerFootnote">
<td style="vertical-align: top; width: 12pt;" valign="top">[1]</td>
<td style="vertical-align: top;" valign="top">We hold our available-for-sale securities at amortized cost.</td>
</tr>
<tr class="outerFootnote">
<td style="vertical-align: top; width: 12pt;" valign="top">[2]</td>
<td style="vertical-align: top;" valign="top">Includes investments classified as cash equivalents on our consolidated balance sheet.</td>
</tr>
<tr class="outerFootnote">
<td style="vertical-align: top; width: 12pt;" valign="top">[3]</td>
<td style="vertical-align: top;" valign="top">Our equity securities included in other current assets consisted of our investments in publicly traded companies. We recognize publicly traded equity securities at fair value.</td>
</tr>
<tr class="outerFootnote">
<td style="vertical-align: top; width: 12pt;" valign="top">[4]</td>
<td style="vertical-align: top;" valign="top">Our equity securities included in deposits and other assets consisted of our investments in privately held companies. We recognize our private company equity securities at 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 on our consolidated balance sheet.</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_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNi">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</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>
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<td><strong> Period Type:</strong></td>
<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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</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>
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<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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</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_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 320<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=121645371&amp;loc=d3e27161-111563<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>
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<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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 320<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)<br> -URI http://asc.fasb.org/extlink&amp;oid=121645371&amp;loc=d3e27161-111563<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>
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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>
</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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 320<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=121645371&amp;loc=d3e27161-111563<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 326<br> -SubTopic 30<br> -Section 45<br> -Paragraph 1<br> -URI http://asc.fasb.org/extlink&amp;oid=121558606&amp;loc=SL82898722-210454<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 942<br> -SubTopic 210<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-03(6))<br> -URI http://asc.fasb.org/extlink&amp;oid=120398452&amp;loc=d3e534808-122878<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 326<br> -SubTopic 30<br> -Section 45<br> -Paragraph 1<br> -URI http://asc.fasb.org/extlink&amp;oid=121558606&amp;loc=SL82898722-210454<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 320<br> -SubTopic 10<br> -Section 45<br> -Paragraph 1<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=121553693&amp;loc=d3e26610-111562<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 320<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (aa)<br> -URI http://asc.fasb.org/extlink&amp;oid=121645371&amp;loc=d3e27161-111563<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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_AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_EquitySecuritiesFvNi">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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).</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 825<br> -SubTopic 10<br> -Section 45<br> -Paragraph 1A<br> -URI http://asc.fasb.org/extlink&amp;oid=99377092&amp;loc=SL75136599-209740<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 321<br> -SubTopic 10<br> -Section 50<br> -Paragraph 4<br> -URI http://asc.fasb.org/extlink&amp;oid=120269885&amp;loc=SL75117546-209714<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 321<br> -SubTopic 10<br> -Section 50<br> -Paragraph 4<br> -URI http://asc.fasb.org/extlink&amp;oid=120269885&amp;loc=SL75117546-209714<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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_InvestmentTypeAxis=us-gaap_DebtSecuritiesMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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_InvestmentTypeAxis=us-gaap_DebtSecuritiesMember</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_InvestmentSecondaryCategorizationAxis=ions_SecuritiesWithMaturityOfOneYearOrLessMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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_InvestmentSecondaryCategorizationAxis=ions_SecuritiesWithMaturityOfOneYearOrLessMember</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_InvestmentSecondaryCategorizationAxis=ions_SecuritiesWithMaturityOfMoreThanOneYearMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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_InvestmentSecondaryCategorizationAxis=ions_SecuritiesWithMaturityOfMoreThanOneYearMember</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_InvestmentTypeAxis=us-gaap_CorporateDebtSecuritiesMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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_InvestmentTypeAxis=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_InvestmentTypeAxis=us-gaap_USGovernmentAgenciesDebtSecuritiesMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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_InvestmentTypeAxis=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_InvestmentTypeAxis=us-gaap_USTreasurySecuritiesMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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_InvestmentTypeAxis=us-gaap_USTreasurySecuritiesMember</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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</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_InvestmentTypeAxis=us-gaap_USStatesAndPoliticalSubdivisionsMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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_InvestmentTypeAxis=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>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_InvestmentTypeAxis=us-gaap_OtherDebtSecuritiesMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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_InvestmentTypeAxis=us-gaap_OtherDebtSecuritiesMember</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>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_InvestmentTypeAxis=us-gaap_EquitySecuritiesMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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_InvestmentTypeAxis=us-gaap_EquitySecuritiesMember</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>
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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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</div></td></tr>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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_InvestmentTypeAxis=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>
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<tr>
<td><strong> Period Type:</strong></td>
<td></td>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_InvestmentTypeAxis=ions_EquitySecuritiesPrivateCompaniesMember">
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<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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_InvestmentTypeAxis=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>
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<td><strong> Balance Type:</strong></td>
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<span style="display: none;">v3.20.4</span><table class="report" border="0" cellspacing="2" id="idm140142735298216">
<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, 2020 </div>
<div>USD ($) </div>
<div>Investment</div>
</th>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesAbstract', window );"><strong>Temporarily Impaired Investments [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableforsaleSecuritiesInUnrealizedLossPositionsQualitativeDisclosureNumberOfPositions1', window );">Number of investments | Investment</a></td>
<td class="nump">226<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThanTwelveMonthsFairValue', window );">Estimated fair value, less than 12 months of temporary impairment</a></td>
<td class="nump">$ 284,148<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss', window );">Unrealized losses, less than 12 months of temporary impairment</a></td>
<td class="num">$ (140)<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_InvestmentTypeAxis=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="top.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="top.Show.showAR( this, 'defref_us-gaap_AvailableforsaleSecuritiesInUnrealizedLossPositionsQualitativeDisclosureNumberOfPositions1', window );">Number of investments | Investment</a></td>
<td class="nump">54<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThanTwelveMonthsFairValue', window );">Estimated fair value, less than 12 months of temporary impairment</a></td>
<td class="nump">$ 121,162<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss', window );">Unrealized losses, less than 12 months of temporary impairment</a></td>
<td class="num">$ (81)<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_InvestmentTypeAxis=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="top.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="top.Show.showAR( this, 'defref_us-gaap_AvailableforsaleSecuritiesInUnrealizedLossPositionsQualitativeDisclosureNumberOfPositions1', window );">Number of investments | Investment</a></td>
<td class="nump">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="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThanTwelveMonthsFairValue', window );">Estimated fair value, less than 12 months of temporary impairment</a></td>
<td class="nump">$ 29,988<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss', window );">Unrealized losses, less than 12 months of temporary impairment</a></td>
<td class="num">$ (11)<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_InvestmentTypeAxis=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="top.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="top.Show.showAR( this, 'defref_us-gaap_AvailableforsaleSecuritiesInUnrealizedLossPositionsQualitativeDisclosureNumberOfPositions1', window );">Number of investments | Investment</a></td>
<td class="nump">8<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThanTwelveMonthsFairValue', window );">Estimated fair value, less than 12 months of temporary impairment</a></td>
<td class="nump">$ 76,941<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss', window );">Unrealized losses, less than 12 months of temporary impairment</a></td>
<td class="num">$ (13)<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_InvestmentTypeAxis=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="top.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="top.Show.showAR( this, 'defref_us-gaap_AvailableforsaleSecuritiesInUnrealizedLossPositionsQualitativeDisclosureNumberOfPositions1', window );">Number of investments | Investment</a></td>
<td class="nump">160<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThanTwelveMonthsFairValue', window );">Estimated fair value, less than 12 months of temporary impairment</a></td>
<td class="nump">$ 49,832<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss', window );">Unrealized losses, less than 12 months of temporary impairment</a></td>
<td class="num">$ (28)<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_InvestmentTypeAxis=us-gaap_OtherDebtSecuritiesMember', window );">Other Municipal Debt Securities [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="top.Show.showAR( this, 'defref_us-gaap_AvailableforsaleSecuritiesInUnrealizedLossPositionsQualitativeDisclosureNumberOfPositions1', window );">Number of investments | Investment</a></td>
<td class="nump">2<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThanTwelveMonthsFairValue', window );">Estimated fair value, less than 12 months of temporary impairment</a></td>
<td class="nump">$ 6,225<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss', window );">Unrealized losses, less than 12 months of temporary impairment</a></td>
<td class="num">$ (7)<span></span>
</td>
</tr>
</table>
<div style="display: none;">
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<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of accumulated unrealized loss on investments in debt and equity securities classified as available-for-sale that have been in a continuous loss position for less than twelve months.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
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<td><strong> Balance Type:</strong></td>
<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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>This item represents the aggregate fair value of investments in debt and equity securities categorized neither as held-to-maturity nor trading securities that have been in a continuous unrealized loss position for less than twelve months.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThanTwelveMonthsFairValue</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<td><strong> Balance Type:</strong></td>
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<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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Number of investment positions in available-for-sale investments in a continuous unrealized loss position for which an other-than-temporary impairment (OTTI) has not been recognized in the income statement.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 320<br> -SubTopic 10<br> -Section 50<br> -Paragraph 6<br> -Subparagraph (b)(3)<br> -URI http://asc.fasb.org/extlink&amp;oid=121645371&amp;loc=d3e27290-111563<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AvailableforsaleSecuritiesInUnrealizedLossPositionsQualitativeDisclosureNumberOfPositions1</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>
<td>na</td>
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<td><strong> Period Type:</strong></td>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
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<a href="javascript:void(0);" onclick="top.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_InvestmentTypeAxis=us-gaap_CorporateDebtSecuritiesMember</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<td><strong> Data Type:</strong></td>
<td>na</td>
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<td><strong> Balance Type:</strong></td>
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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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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_InvestmentTypeAxis=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>
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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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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_InvestmentTypeAxis=us-gaap_USTreasurySecuritiesMember</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<td><strong> Data Type:</strong></td>
<td>na</td>
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<td><strong> Balance Type:</strong></td>
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<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
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<td style="white-space:nowrap;">us-gaap_InvestmentTypeAxis=us-gaap_USStatesAndPoliticalSubdivisionsMember</td>
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<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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_InvestmentTypeAxis=us-gaap_OtherDebtSecuritiesMember</td>
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<span style="display: none;">v3.20.4</span><table class="report" border="0" cellspacing="2" id="idm140142741299880">
<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" colspan="2"><div>Dec. 31, 2020</div></th>
<th class="th"><div>Dec. 31, 2019</div></th>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_LoansPayableToBank', window );">Long-term mortgage debt</a></td>
<td class="nump">$ 59,984<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">$ 59,913<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_LeasesAndOtherObligations', window );">Leases and other obligations</a></td>
<td class="nump">30,710<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">17,569<span></span>
</td>
</tr>
<tr class="rou">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_DebtAndCapitalLeaseObligations', window );">Total</a></td>
<td class="nump">839,574<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">787,526<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_LongTermDebtAndCapitalLeaseObligationsCurrent', window );">Less: current portion</a></td>
<td class="num">(300,462)<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="num">(2,026)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_LongTermDebtAndCapitalLeaseObligations', window );">Total Long-Term Obligations</a></td>
<td class="nump">539,112<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">785,500<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes0125PercentMember', window );">0.125 Percent Convertible Senior Notes [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ConvertibleDebt', window );">Convertible senior notes</a></td>
<td class="nump">$ 455,719<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">$ 434,711<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_DebtInstrumentInterestRateStatedPercentage', window );">Interest rate on convertible senior notes</a></td>
<td class="nump">0.125%<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">0.125%<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes1PercentMember', window );">1 Percent Convertible Senior Notes [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ConvertibleDebt', window );">Convertible senior notes</a></td>
<td class="nump">$ 293,161<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"><sup>[1]</sup></td>
<td class="nump">$ 275,333<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_DebtInstrumentInterestRateStatedPercentage', window );">Interest rate on convertible senior notes</a></td>
<td class="nump">1.00%<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">1.00%<span></span>
</td>
</tr>
<tr><td colspan="4"></td></tr>
<tr><td colspan="4"><table class="outerFootnotes" width="100%"><tr class="outerFootnote">
<td style="vertical-align: top; width: 12pt;" valign="top">[1]</td>
<td style="vertical-align: top;" valign="top">We classified the carrying value of our 1% Notes as a current liability on our consolidated balance sheet at December 31, 2020 because it matures in November 2021.</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_LeasesAndOtherObligations">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Present value of lessee's discounted obligation for lease payments and the aggregate of other miscellaneous borrowings owed.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_LeasesAndOtherObligations</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: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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 944<br> -SubTopic 210<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-03(a)(16))<br> -URI http://asc.fasb.org/extlink&amp;oid=120400017&amp;loc=d3e572229-122910<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(22))<br> -URI http://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 942<br> -SubTopic 210<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-03(16))<br> -URI http://asc.fasb.org/extlink&amp;oid=120398452&amp;loc=d3e534808-122878<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>
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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>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DebtAndCapitalLeaseObligations">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of short-term and long-term debt and lease obligation.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 942<br> -SubTopic 210<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-03.13,16)<br> -URI http://asc.fasb.org/extlink&amp;oid=120398452&amp;loc=d3e534808-122878<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 944<br> -SubTopic 210<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-03.16)<br> -URI http://asc.fasb.org/extlink&amp;oid=120400017&amp;loc=d3e572229-122910<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DebtAndCapitalLeaseObligations</td>
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<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</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_DebtInstrumentInterestRateStatedPercentage">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02.22(a)(1))<br> -URI http://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DebtInstrumentInterestRateStatedPercentage</td>
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<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<tr>
<td><strong> Data Type:</strong></td>
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<td><strong> Balance Type:</strong></td>
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<td><strong> Period Type:</strong></td>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(22))<br> -URI http://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 944<br> -SubTopic 210<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-03(16)(a))<br> -URI http://asc.fasb.org/extlink&amp;oid=120400017&amp;loc=d3e572229-122910<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 942<br> -SubTopic 210<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-03(16))<br> -URI http://asc.fasb.org/extlink&amp;oid=120398452&amp;loc=d3e534808-122878<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_LoansPayableToBank</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<tr>
<td><strong> Data Type:</strong></td>
<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_LongTermDebtAndCapitalLeaseObligations">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of long-term debt and lease obligation, classified as noncurrent.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(22))<br> -URI http://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_LongTermDebtAndCapitalLeaseObligations</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>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_LongTermDebtAndCapitalLeaseObligationsCurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of long-term debt and lease obligation, classified as current.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02.20)<br> -URI http://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_LongTermDebtAndCapitalLeaseObligationsCurrent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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_DebtInstrumentAxis=ions_ConvertibleSeniorNotes0125PercentMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes0125PercentMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes1PercentMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes1PercentMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
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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></div>
</div></td></tr>
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<DOCUMENT>
<TYPE>XML
<SEQUENCE>91
<FILENAME>R55.htm
<DESCRIPTION>IDEA: XBRL DOCUMENT
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<head>
<title></title>
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<span style="display: none;">v3.20.4</span><table class="report" border="0" cellspacing="2" id="idm140142735814360">
<tr>
<th class="tl" colspan="2" rowspan="2"><div style="width: 200px;"><strong>Long-Term Obligations and Commitments, Convertible Notes (Details)<br> $ / shares in Units, $ in Thousands, shares in Millions</strong></div></th>
<th class="th" colspan="1">1 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, 2019 </div>
<div>USD ($) </div>
<div>$ / shares</div>
</th>
<th class="th">
<div>Dec. 31, 2020 </div>
<div>USD ($) </div>
<div>shares </div>
<div>$ / shares</div>
</th>
<th class="th">
<div>Dec. 31, 2019 </div>
<div>USD ($) </div>
<div>$ / shares</div>
</th>
<th class="th">
<div>Dec. 31, 2018 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Dec. 31, 2016 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Nov. 30, 2014 </div>
<div>USD ($)</div>
</th>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract', window );"><strong>Convertible Notes [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_CallSpread', window );">Cost of call spread</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">$ 52,600<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_PaymentsForHedgeFinancingActivities', window );">Purchase of note hedges</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">108,700<span></span>
</td>
<td class="nump">$ 0<span></span>
</td>
<td class="nump">$ 108,684<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 " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ProceedsFromIssuanceOfWarrants', window );">Proceeds from issuance of warrants</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">$ 56,100<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">$ 56,110<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 custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_DebtInstrumentConvertibleConversionPriceIncludingCallSpread', window );">Conversion price per share, including note hedges (in dollars per share) | $ / shares</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">$ 123.38<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 123.38<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ConvertibleDebtCurrent', window );">Current debt</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">$ 0<span></span>
</td>
<td class="nump">293,161<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="top.Show.showAR( this, 'defref_us-gaap_GainsLossesOnExtinguishmentOfDebt', window );">Loss on early retirement of debt</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>
<td class="num">(21,865)<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 " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AmortizationOfFinancingCostsAndDiscounts', window );">Amortization of debt discount and debt issuance costs</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 38,700<span></span>
</td>
<td class="nump">$ 39,300<span></span>
</td>
<td class="nump">$ 35,200<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="top.Show.showAR( this, 'defref_us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes0125PercentMember', window );">0.125% Convertible Senior Notes [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract', window );"><strong>Convertible Notes [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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_DebtInstrumentMaturityDate', window );">Maturity date</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">Dec. 15,  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="top.Show.showAR( this, 'defref_us-gaap_DebtInstrumentInterestRateStatedPercentage', window );">Interest rate</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></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="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_DebtInstrumentConvertibleConversionPrice1', window );">Conversion price per share (in dollars per share) | $ / shares</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></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="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_DebtInstrumentConvertibleNumberOfEquityInstruments', window );">Total shares of common stock subject to conversion (in shares) | shares</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">6.6<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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="top.Show.showAR( this, 'defref_ions_DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange', window );">Percentage of principal amount used as purchase price upon occurrence of fundamental change</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></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="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_DebtInstrumentCarryingAmount', window );">Principal amount of convertible notes outstanding</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">$ 548,800<span></span>
</td>
<td class="nump">$ 548,800<span></span>
</td>
<td class="nump">$ 548,800<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_DebtInstrumentUnamortizedDiscountPremiumNet', window );">Unamortized portion of debt discount</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">105,200<span></span>
</td>
<td class="nump">86,000<span></span>
</td>
<td class="nump">105,200<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ConvertibleDebtNoncurrent', window );">Long-term debt</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">434,711<span></span>
</td>
<td class="nump">455,719<span></span>
</td>
<td class="nump">434,711<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_DebtInstrumentConvertibleCarryingAmountOfTheEquityComponent', window );">Carrying value of equity component</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">105,800<span></span>
</td>
<td class="nump">$ 105,800<span></span>
</td>
<td class="nump">105,800<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_DebtInstrumentInterestRateEffectivePercentage', window );">Effective interest rate</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">4.90%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_DebtInstrumentConvertibleRemainingDiscountAmortizationPeriod1', window );">Amortization period of debt discount</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></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>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes0125PercentMember', window );">0.125% Convertible Senior Notes [Member] | Level 2 [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract', window );"><strong>Convertible Notes [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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_LongTermDebtFairValue', window );">Fair value of outstanding notes</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">558,700<span></span>
</td>
<td class="nump">$ 564,900<span></span>
</td>
<td class="nump">558,700<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes0125PercentMember', window );">0.125% Convertible Senior Notes [Member] | Borrowing Rate [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract', window );"><strong>Convertible Notes [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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_DebtInstrumentMeasurementInput', window );">Nonconvertible debt measurement input rate</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">0.044<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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="top.Show.showAR( this, 'defref_us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes0125PercentIssuedInExchangeFor1PercentNotesMember', window );">0.125 Percent Convertible Senior Notes Issued in Exchange for 1 Percent Notes [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract', window );"><strong>Convertible Notes [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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_DebtInstrumentFaceAmount', window );">Face amount of offering</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">439,300<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">439,300<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes0125PercentIssuedUnderSubscriptionAgreementsMember', window );">0.125 Percent Convertible Senior Notes Issued under Subscription Agreements [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract', window );"><strong>Convertible Notes [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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_DebtInstrumentFaceAmount', window );">Face amount of offering</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">109,500<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">109,500<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes1PercentMember', window );">1% Convertible Senior Notes [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract', window );"><strong>Convertible Notes [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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_DebtInstrumentRepurchasedFaceAmount', window );">Principal amount repurchased</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">$ 375,600<span></span>
</td>
<td class="text">&#160;<span></span>
</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="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_DebtInstrumentFaceAmount', window );">Face amount of offering</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 185,500<span></span>
</td>
<td class="nump">$ 500,000<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_DebtInstrumentMaturityDate', window );">Maturity date</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">Nov. 30,  2021<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_DebtInstrumentInterestRateStatedPercentage', window );">Interest rate</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">1.00%<span></span>
</td>
<td class="nump">1.00%<span></span>
</td>
<td class="nump">1.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_DebtInstrumentConvertibleConversionPrice1', window );">Conversion price per share (in dollars per share) | $ / shares</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 66.81<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_DebtInstrumentConvertibleNumberOfEquityInstruments', window );">Total shares of common stock subject to conversion (in shares) | shares</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">4.6<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange', window );">Percentage of principal amount used as purchase price upon occurrence of fundamental change</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></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="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_DebtInstrumentCarryingAmount', window );">Principal amount of convertible notes outstanding</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">$ 309,900<span></span>
</td>
<td class="nump">$ 309,900<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>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_DebtInstrumentUnamortizedDiscountPremiumNet', window );">Unamortized portion of debt discount</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">32,800<span></span>
</td>
<td class="nump">15,800<span></span>
</td>
<td class="nump">32,800<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ConvertibleDebtCurrent', window );">Current debt</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">293,200<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="top.Show.showAR( this, 'defref_us-gaap_ConvertibleDebtNoncurrent', window );">Long-term debt</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">275,333<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">275,333<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_DebtInstrumentConvertibleCarryingAmountOfTheEquityComponent', window );">Carrying value of equity component</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">33,500<span></span>
</td>
<td class="nump">$ 33,500<span></span>
</td>
<td class="nump">33,500<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_GainsLossesOnExtinguishmentOfDebt', window );">Loss on early retirement of debt</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="num">(21,900)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_DebtInstrumentInterestRateEffectivePercentage', window );">Effective interest rate</a></td>
<td class="th" style="border-bottom: 0px;"><sup>[1]</sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">7.50%<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="top.Show.showAR( this, 'defref_us-gaap_DebtInstrumentConvertibleRemainingDiscountAmortizationPeriod1', window );">Amortization period of debt discount</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">7 years<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes1PercentMember', window );">1% Convertible Senior Notes [Member] | Level 2 [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract', window );"><strong>Convertible Notes [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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_LongTermDebtFairValue', window );">Fair value of outstanding notes</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">$ 354,800<span></span>
</td>
<td class="nump">$ 338,500<span></span>
</td>
<td class="nump">$ 354,800<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes1PercentMember', window );">1% Convertible Senior Notes [Member] | Borrowing Rate [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract', window );"><strong>Convertible Notes [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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_DebtInstrumentMeasurementInput', window );">Nonconvertible debt measurement input rate</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">0.074<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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="top.Show.showAR( this, 'defref_us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes275PercentMember', window );">2 3/4 Percent Convertible Senior Notes [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract', window );"><strong>Convertible Notes [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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_DebtInstrumentRepurchasedFaceAmount', window );">Principal amount repurchased</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 61,100<span></span>
</td>
<td class="nump">$ 140,000<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_DebtInstrumentInterestRateStatedPercentage', window );">Interest rate</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">2.75%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr><td colspan="7"></td></tr>
<tr><td colspan="7"><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">For our 1% Notes, our effective interest rate represents our effective interest rate after our December 2019 debt exchange.</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_CallSpread">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.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> Balance Type:</strong></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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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.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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</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AmortizationOfFinancingCostsAndDiscounts">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of amortization expense attributable to debt discount (premium) and debt issuance costs.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=121586364&amp;loc=d3e3602-108585<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 835<br> -SubTopic 30<br> -Section 45<br> -Paragraph 3<br> -URI http://asc.fasb.org/extlink&amp;oid=119993939&amp;loc=d3e28555-108399<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AmortizationOfFinancingCostsAndDiscounts</td>
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<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
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</tr>
</table></div>
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</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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(19))<br> -URI http://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>
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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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02.22)<br> -URI http://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>
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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>
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</table></div>
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</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>
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<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
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<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
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<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
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<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_DebtInstrumentCarryingAmount">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 20<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (b)(1)<br> -URI http://asc.fasb.org/extlink&amp;oid=120520924&amp;loc=SL6031897-161870<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 944<br> -SubTopic 210<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-03(16))<br> -URI http://asc.fasb.org/extlink&amp;oid=120400017&amp;loc=d3e572229-122910<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(22))<br> -URI http://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 942<br> -SubTopic 210<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-03(16))<br> -URI http://asc.fasb.org/extlink&amp;oid=120398452&amp;loc=d3e534808-122878<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>
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<td><strong> Balance Type:</strong></td>
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<td><strong> Period Type:</strong></td>
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</div></td></tr>
</table>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The carrying amount of the equity component of convertible debt which may be settled in cash upon conversion.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 20<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=120520924&amp;loc=SL6031897-161870<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DebtInstrumentConvertibleCarryingAmountOfTheEquityComponent</td>
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<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 20<br> -Section 50<br> -Paragraph 5<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=120520924&amp;loc=SL6031898-161870<br></p></div>
<a href="javascript:void(0);" onclick="top.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> Balance Type:</strong></td>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
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<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The number of equity instruments that the holder of the debt instrument would receive if the debt was converted to equity.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 505<br> -SubTopic 10<br> -Section 50<br> -Paragraph 3<br> -URI http://asc.fasb.org/extlink&amp;oid=109259400&amp;loc=d3e21475-112644<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 505<br> -SubTopic 10<br> -Section 50<br> -Paragraph 7<br> -URI http://asc.fasb.org/extlink&amp;oid=109259400&amp;loc=d3e21521-112644<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 505<br> -SubTopic 10<br> -Section 50<br> -Paragraph 6<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=109259400&amp;loc=d3e21506-112644<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02.22(a)(5))<br> -URI http://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="top.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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</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DebtInstrumentConvertibleRemainingDiscountAmortizationPeriod1">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Remaining amortization period for discount on the liability component of convertible debt which may be settled in cash upon conversion, 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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 20<br> -Section 50<br> -Paragraph 5<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=120520924&amp;loc=SL6031898-161870<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DebtInstrumentConvertibleRemainingDiscountAmortizationPeriod1</td>
</tr>
<tr>
<td style="padding-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_DebtInstrumentFaceAmount">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 835<br> -SubTopic 30<br> -Section 45<br> -Paragraph 2<br> -URI http://asc.fasb.org/extlink&amp;oid=119993939&amp;loc=d3e28551-108399<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 835<br> -SubTopic 30<br> -Section 55<br> -Paragraph 8<br> -URI http://asc.fasb.org/extlink&amp;oid=114775985&amp;loc=d3e28878-108400<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 20<br> -Section 50<br> -Paragraph 6<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=120520924&amp;loc=SL6036836-161870<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 835<br> -SubTopic 30<br> -Section 45<br> -Paragraph 2<br> -URI http://asc.fasb.org/extlink&amp;oid=119993939&amp;loc=d3e28551-108399<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02.22(a)(1))<br> -URI http://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>num: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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02.22(a)(1))<br> -URI http://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>num:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DebtInstrumentMaturityDate">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Date when the debt instrument is scheduled to be fully repaid, in CCYY-MM-DD format.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02.22(a)(2))<br> -URI http://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br><br>Reference 2: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 820<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (bbb)(2)<br> -URI http://asc.fasb.org/extlink&amp;oid=117815213&amp;loc=d3e19207-110258<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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_DebtInstrumentMeasurementInput">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Value of input used to measure debt instrument, including, but not limited to, convertible and non-convertible debt.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 820<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (bbb)(2)<br> -URI http://asc.fasb.org/extlink&amp;oid=117815213&amp;loc=d3e19207-110258<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DebtInstrumentMeasurementInput</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:decimalItemType</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_DebtInstrumentRepurchasedFaceAmount">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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_DebtInstrumentUnamortizedDiscountPremiumNet">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount, after accumulated amortization, of debt discount (premium).</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 835<br> -SubTopic 30<br> -Section 45<br> -Paragraph 3<br> -URI http://asc.fasb.org/extlink&amp;oid=119993939&amp;loc=d3e28555-108399<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 835<br> -SubTopic 30<br> -Section 45<br> -Paragraph 2<br> -URI http://asc.fasb.org/extlink&amp;oid=119993939&amp;loc=d3e28551-108399<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 835<br> -SubTopic 30<br> -Section 45<br> -Paragraph 4<br> -URI http://asc.fasb.org/extlink&amp;oid=119993939&amp;loc=d3e28567-108399<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 835<br> -SubTopic 30<br> -Section 45<br> -Paragraph 1A<br> -URI http://asc.fasb.org/extlink&amp;oid=119993939&amp;loc=d3e28541-108399<br><br>Reference 5: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 835<br> -SubTopic 30<br> -Section 55<br> -Paragraph 8<br> -URI http://asc.fasb.org/extlink&amp;oid=114775985&amp;loc=d3e28878-108400<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DebtInstrumentUnamortizedDiscountPremiumNet</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 50<br> -Section 40<br> -Paragraph 4<br> -URI http://asc.fasb.org/extlink&amp;oid=117329964&amp;loc=d3e12355-112629<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 50<br> -Section 40<br> -Paragraph 2<br> -URI http://asc.fasb.org/extlink&amp;oid=117329964&amp;loc=d3e12317-112629<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=121586364&amp;loc=d3e3602-108585<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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_LongTermDebtFairValue">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The fair value amount of long-term debt whether such amount is presented as a separate caption or as a parenthetical disclosure. Additionally, this element may be used in connection with the fair value disclosures required in the footnote disclosures to the financial statements. The element may be used in both the balance sheet and disclosure in the same submission.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_LongTermDebtFairValue</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>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_PaymentsForHedgeFinancingActivities">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 15<br> -URI http://asc.fasb.org/extlink&amp;oid=121586364&amp;loc=d3e3291-108585<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 27<br> -URI http://asc.fasb.org/extlink&amp;oid=121586364&amp;loc=d3e3581-108585<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PaymentsForHedgeFinancingActivities</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ProceedsFromIssuanceOfWarrants">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 14<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=121586364&amp;loc=d3e3255-108585<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>
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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>
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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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes0125PercentMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<td><strong> Data Type:</strong></td>
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<td><strong> Balance Type:</strong></td>
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<td><strong> Period Type:</strong></td>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_FairValueByFairValueHierarchyLevelAxis=us-gaap_FairValueInputsLevel2Member">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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_FairValueByFairValueHierarchyLevelAxis=us-gaap_FairValueInputsLevel2Member</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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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_MeasurementInputTypeAxis=us-gaap_MeasurementInputDiscountRateMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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_MeasurementInputTypeAxis=us-gaap_MeasurementInputDiscountRateMember</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>
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<td></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_us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes0125PercentIssuedInExchangeFor1PercentNotesMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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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<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 class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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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<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 class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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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<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><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes275PercentMember</td>
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<span style="display: none;">v3.20.4</span><table class="report" border="0" cellspacing="2" id="idm140142736641528">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Long-Term Obligations and Commitments, Line of Credit Arrangement (Details) - USD ($)<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>Sep. 30, 2019</div></th>
<th class="th"><div>Dec. 31, 2020</div></th>
<th class="th"><div>Dec. 31, 2019</div></th>
<th class="th"><div>Dec. 31, 2018</div></th>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_LineOfCreditFacilityAbstract', window );"><strong>Line of Credit Arrangement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RepaymentsOfLongTermLinesOfCredit', window );">Payment of outstanding borrowings</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 0<span></span>
</td>
<td class="nump">$ 12,500<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="top.Show.showAR( this, 'defref_us-gaap_DebtInstrumentAxis=ions_FixedRateNoteWithMorganStanleyMember', window );">Fixed Rate Note with Morgan Stanley [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="top.Show.showAR( this, 'defref_us-gaap_LineOfCreditFacilityAbstract', window );"><strong>Line of Credit Arrangement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RepaymentsOfLongTermLinesOfCredit', window );">Payment of outstanding borrowings</a></td>
<td class="nump">$ 12,500<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_LineOfCreditFacilityAxis=ions_MorganStanleyPrivateBankNationalAssociationMember', window );">Morgan Stanley [Member] | Revolving Line of Credit [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="top.Show.showAR( this, 'defref_us-gaap_LineOfCreditFacilityAbstract', window );"><strong>Line of Credit Arrangement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_DebtInstrumentTerm', window );">Term of agreement</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>
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<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_LineOfCreditFacilityMaximumBorrowingCapacity', window );">Maximum borrowing capacity</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 30,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
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<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DebtInstrumentTerm">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Period of time between issuance and maturity of debt instrument, 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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DebtInstrumentTerm</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 class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_LineOfCreditFacilityAbstract</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>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_LineOfCreditFacilityMaximumBorrowingCapacity">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Maximum borrowing capacity under the credit facility without consideration of any current restrictions on the amount that could be borrowed or the amounts currently outstanding under the facility.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02.19(b),22(b))<br> -URI http://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_LineOfCreditFacilityMaximumBorrowingCapacity</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>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_RepaymentsOfLongTermLinesOfCredit">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The cash outflow for the settlement of obligation drawn from a contractual arrangement with the lender, including letter of credit, standby letter of credit and revolving credit arrangements, under which borrowings can be made up to a specific amount at any point in time with maturities due beyond one year or the operating cycle, if longer.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 15<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=121586364&amp;loc=d3e3291-108585<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_RepaymentsOfLongTermLinesOfCredit</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>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>
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</table></div>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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_FixedRateNoteWithMorganStanleyMember</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>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>
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<a href="javascript:void(0);" onclick="top.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_LineOfCreditFacilityAxis=ions_MorganStanleyPrivateBankNationalAssociationMember</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>
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<td><strong> Period Type:</strong></td>
<td></td>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_CreditFacilityAxis=us-gaap_RevolvingCreditFacilityMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
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<a href="javascript:void(0);" onclick="top.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_CreditFacilityAxis=us-gaap_RevolvingCreditFacilityMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
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<td><strong> Data Type:</strong></td>
<td>na</td>
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<td><strong> Balance Type:</strong></td>
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<DOCUMENT>
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<DESCRIPTION>IDEA: XBRL DOCUMENT
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<head>
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<span style="display: none;">v3.20.4</span><table class="report" border="0" cellspacing="2" id="idm140142724579944">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Long-Term Obligations and Commitments, Research and Development and Manufacturing Facilities (Details)<br> $ in Millions</strong></div></th>
<th class="th" colspan="2">1 Months Ended</th>
<th class="th" colspan="1">12 Months Ended</th>
</tr>
<tr>
<th class="th">
<div>Jul. 31, 2017 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Jul. 31, 2015 </div>
<div>Facility</div>
</th>
<th class="th"><div>Dec. 31, 2020</div></th>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_PaymentsToAcquirePropertyPlantAndEquipmentAbstract', window );"><strong>Research and Development and Manufacturing 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>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_NumberOfPurchasedFacilitiesFinancedWithMortgageDebt', window );">Number of purchased facilities financed with mortgage debt | Facility</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">2<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_PaymentsToAcquirePropertyPlantAndEquipmentAbstract', window );"><strong>Research and Development and Manufacturing 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>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_DebtInstrumentFaceAmount', window );">Face amount</a></td>
<td class="nump">$ 60.4<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="top.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>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_PaymentsToAcquirePropertyPlantAndEquipmentAbstract', window );"><strong>Research and Development and Manufacturing 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>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_PaymentsToAcquireBuildings', window );">Payment to acquire building</a></td>
<td class="nump">$ 79.4<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_DebtInstrumentInterestRateStatedPercentage', window );">Interest rate</a></td>
<td class="nump">3.88%<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="top.Show.showAR( this, 'defref_ions_PeriodToMakeInterestOnlyPaymentsOnMortgageLoan', window );">Period to make interest only payments on mortgage loan</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">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="top.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>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_PaymentsToAcquirePropertyPlantAndEquipmentAbstract', window );"><strong>Research and Development and Manufacturing 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>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_PaymentsToAcquireBuildings', window );">Payment to acquire building</a></td>
<td class="nump">$ 14.0<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_DebtInstrumentInterestRateStatedPercentage', window );">Interest rate</a></td>
<td class="nump">4.20%<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="top.Show.showAR( this, 'defref_ions_PeriodToMakeInterestOnlyPaymentsOnMortgageLoan', window );">Period to make interest only payments on mortgage loan</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">5 years<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_NumberOfPurchasedFacilitiesFinancedWithMortgageDebt">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The number of purchased facilities financed with mortgage debt.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</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>
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<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:durationItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
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<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DebtInstrumentFaceAmount">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 835<br> -SubTopic 30<br> -Section 45<br> -Paragraph 2<br> -URI http://asc.fasb.org/extlink&amp;oid=119993939&amp;loc=d3e28551-108399<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 835<br> -SubTopic 30<br> -Section 55<br> -Paragraph 8<br> -URI http://asc.fasb.org/extlink&amp;oid=114775985&amp;loc=d3e28878-108400<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DebtInstrumentInterestRateStatedPercentage">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02.22(a)(1))<br> -URI http://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>num:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_PaymentsToAcquireBuildings">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 13<br> -Subparagraph (c)<br> -URI http://asc.fasb.org/extlink&amp;oid=121586364&amp;loc=d3e3213-108585<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>
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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_PaymentsToAcquirePropertyPlantAndEquipmentAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PaymentsToAcquirePropertyPlantAndEquipmentAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DebtInstrumentAxis=ions_LongTermMortgageDebtMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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_PropertyPlantAndEquipmentByTypeAxis=ions_PrimaryResearchAndDevelopmentFacilityMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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>
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<html>
<head>
<title></title>
<link rel="stylesheet" type="text/css" href="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;">v3.20.4</span><table class="report" border="0" cellspacing="2" id="idm140142736337944">
<tr>
<th class="tl" colspan="1" rowspan="1"><div style="width: 200px;"><strong>Long-Term Obligations and Commitments, Maturity Schedules (Details) - USD ($)<br> $ in Thousands</strong></div></th>
<th class="th"><div>Dec. 31, 2020</div></th>
<th class="th"><div>Dec. 31, 2019</div></th>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_MaturitiesOfLongtermDebtAndCapitalLeaseObligationsAbstract', window );"><strong>Annual Debt and Other Obligation Maturities [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="top.Show.showAR( this, 'defref_us-gaap_ContractualObligationDueInNextTwelveMonths', window );">2021</a></td>
<td class="nump">$ 329,189<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ContractualObligationDueInSecondYear', window );">2022</a></td>
<td class="nump">3,495<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ContractualObligationDueInThirdYear', window );">2023</a></td>
<td class="nump">4,180<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ContractualObligationDueInFourthYear', window );">2024</a></td>
<td class="nump">553,006<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ContractualObligationDueInFifthYear', window );">2025</a></td>
<td class="nump">3,494<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ContractualObligationDueAfterFifthYear', window );">Thereafter</a></td>
<td class="nump">60,933<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="top.Show.showAR( this, 'defref_us-gaap_ContractualObligation', window );">Subtotal</a></td>
<td class="nump">954,297<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_LongTermDebtAndCapitalLeaseObligationsCurrent', window );">Less: current portion</a></td>
<td class="num">(300,462)<span></span>
</td>
<td class="num">$ (2,026)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_InterestPayableCurrentAndNoncurrent', window );">Less: fixed and determinable interest</a></td>
<td class="num">(21,758)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_DebtInstrumentUnamortizedDiscount', window );">Less: unamortized portion of debt discount</a></td>
<td class="num">(101,820)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_DeferredFinanceCostsNet', window );">Less: debt issuance costs</a></td>
<td class="num">(8,455)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_DeferredRentCredit', window );">Plus: lease liabilities</a></td>
<td class="nump">17,310<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_LongTermDebtAndCapitalLeaseObligations', window );">Total long-term debt</a></td>
<td class="nump">$ 539,112<span></span>
</td>
<td class="nump">$ 785,500<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_ContractualObligation">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of contractual obligation, including but not limited to, long-term debt, capital lease obligations, operating lease obligations, purchase obligations, and other commitments.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ContractualObligation</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>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_ContractualObligationDueAfterFifthYear">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of contractual obligation to be paid 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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ContractualObligationDueAfterFifthYear</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>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_ContractualObligationDueInFifthYear">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of contractual obligation 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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ContractualObligationDueInFifthYear</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>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_ContractualObligationDueInFourthYear">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of contractual obligation 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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ContractualObligationDueInFourthYear</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>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_ContractualObligationDueInNextTwelveMonths">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of contractual obligation 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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ContractualObligationDueInNextTwelveMonths</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>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_ContractualObligationDueInSecondYear">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of contractual obligation 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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ContractualObligationDueInSecondYear</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>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_ContractualObligationDueInThirdYear">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of contractual obligation 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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ContractualObligationDueInThirdYear</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>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_DebtInstrumentUnamortizedDiscount">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount, after accumulated amortization, of debt discount.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 835<br> -SubTopic 30<br> -Section 45<br> -Paragraph 1A<br> -URI http://asc.fasb.org/extlink&amp;oid=119993939&amp;loc=d3e28541-108399<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 835<br> -SubTopic 30<br> -Section 55<br> -Paragraph 8<br> -URI http://asc.fasb.org/extlink&amp;oid=114775985&amp;loc=d3e28878-108400<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DebtInstrumentUnamortizedDiscount</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02.17)<br> -URI http://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 835<br> -SubTopic 30<br> -Section 45<br> -Paragraph 3<br> -URI http://asc.fasb.org/extlink&amp;oid=119993939&amp;loc=d3e28555-108399<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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_DeferredRentCredit">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The cumulative difference between the rental payments required by a lease agreement and the rental income or expense recognized on a straight-line basis, or other systematic and rational basis more representative of the time pattern in which use or benefit is granted or derived from the leased property, expected to be recognized in income or expense over the term of the leased property by the lessor or lessee, respectively.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 840<br> -SubTopic 20<br> -Section 25<br> -Paragraph 1<br> -URI http://asc.fasb.org/extlink&amp;oid=121549951&amp;loc=d3e39896-112707<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DeferredRentCredit</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>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_InterestPayableCurrentAndNoncurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 942<br> -SubTopic 210<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-03.15(5))<br> -URI http://asc.fasb.org/extlink&amp;oid=120398452&amp;loc=d3e534808-122878<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 944<br> -SubTopic 210<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-03.15(a))<br> -URI http://asc.fasb.org/extlink&amp;oid=120400017&amp;loc=d3e572229-122910<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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_LongTermDebtAndCapitalLeaseObligations">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of long-term debt and lease obligation, classified as noncurrent.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(22))<br> -URI http://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_LongTermDebtAndCapitalLeaseObligations</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>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_LongTermDebtAndCapitalLeaseObligationsCurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of long-term debt and lease obligation, classified as current.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02.20)<br> -URI http://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_LongTermDebtAndCapitalLeaseObligationsCurrent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>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_MaturitiesOfLongtermDebtAndCapitalLeaseObligationsAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_MaturitiesOfLongtermDebtAndCapitalLeaseObligationsAbstract</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>
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</div></td></tr>
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<span style="display: none;">v3.20.4</span><table class="report" border="0" cellspacing="2" id="idm140142735016680">
<tr>
<th class="tl" colspan="2" 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="3">12 Months Ended</th>
</tr>
<tr>
<th class="th">
<div>Dec. 31, 2020 </div>
<div>USD ($) </div>
<div>Option</div>
</th>
<th class="th">
<div>Dec. 31, 2019 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Dec. 31, 2018 </div>
<div>USD ($)</div>
</th>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_LesseeDisclosureAbstract', window );"><strong>Operating Leases [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_OperatingLeaseRightOfUseAsset', window );">Right-of-use operating lease assets</a></td>
<td class="th" style="border-bottom: 0px;"><sup>[1]</sup></td>
<td class="nump">$ 13,100<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_OperatingLeaseRightOfUseAssetStatementOfFinancialPositionExtensibleList', window );">Operating Lease, Right-of-Use Asset, Statement of Financial Position [Extensible List]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">us-gaap:OtherAssetsNoncurrent<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_OperatingLeaseLiability', window );">Operating lease liabilities</a></td>
<td class="th" style="border-bottom: 0px;"><sup>[2]</sup></td>
<td class="nump">$ 17,310<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_OperatingLeaseWeightedAverageRemainingLeaseTerm1', window );">Weighted average remaining lease term</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">7 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="top.Show.showAR( this, 'defref_us-gaap_OperatingLeaseWeightedAverageDiscountRatePercent', window );">Weighted average discount rate</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></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="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_OperatingLeaseLiabilityCurrent', window );">Current portion of operating lease liabilities</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">$ 2,000<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="top.Show.showAR( this, 'defref_us-gaap_OperatingLeaseLiabilityCurrentStatementOfFinancialPositionExtensibleList', window );">Operating Lease, Liability, Current, Statement of Financial Position [Extensible List]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">us-gaap:LongTermDebtAndCapitalLeaseObligationsCurrent<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_OperatingLeaseLiabilityNoncurrentStatementOfFinancialPositionExtensibleList', window );">Operating Lease, Liability, Noncurrent, Statement of Financial Position [Extensible List]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">ions:LongTermObligationsNoncurrent<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_OperatingLeasePayments', window );">Operating lease cash payments</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">$ 3,800<span></span>
</td>
<td class="nump">$ 3,900<span></span>
</td>
<td class="nump">$ 1,700<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_OperatingLeaseLiabilitiesPaymentsDueAbstract', window );"><strong>Annual Future Payments for Operating Lease Liabilities [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>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueNextTwelveMonths', window );">2021</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">3,193<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearTwo', window );">2022</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">2,968<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearThree', window );">2023</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">2,707<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearFour', window );">2024</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">2,583<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearFive', window );">2025</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">2,442<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueAfterYearFive', window );">Thereafter</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">7,038<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="top.Show.showAR( this, 'defref_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue', window );">Total minimum lease payments</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">20,931<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_LesseeOperatingLeaseLiabilityUndiscountedExcessAmount', window );">Imputed interest</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="num">(3,621)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_OperatingLeaseLiability', window );">Total operating lease liabilities</a></td>
<td class="th" style="border-bottom: 0px;"><sup>[2]</sup></td>
<td class="nump">17,310<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_OperatingLeaseExpense', window );">Rent expense</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">$ 3,700<span></span>
</td>
<td class="nump">$ 3,600<span></span>
</td>
<td class="nump">$ 2,600<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_GeographicDistributionAxis=ions_CarlsbadFacilityMember', window );">Carlsbad Facility [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_LesseeDisclosureAbstract', window );"><strong>Operating Leases [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>
<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="top.Show.showAR( this, 'defref_ions_LesseeLeasingArrangementsOperatingLeasesNumberOfOptionsToExtendLease', window );">Number of options to extend lease | Option</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></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="top.Show.showAR( this, 'defref_us-gaap_LesseeOperatingLeaseRenewalTerm', window );">Term of lease extension</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></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="top.Show.showAR( this, 'defref_us-gaap_GeographicDistributionAxis=ions_CarlsbadOfficeSpacesMember', window );">Carlsbad Office Spaces [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_LesseeDisclosureAbstract', window );"><strong>Operating Leases [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>
<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="top.Show.showAR( this, 'defref_ions_LesseeLeasingArrangementsOperatingLeasesNumberOfOptionsToExtendLease', window );">Number of options to extend lease | Option</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></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="top.Show.showAR( this, 'defref_us-gaap_LesseeOperatingLeaseRenewalTerm', window );">Term of lease extension</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></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="top.Show.showAR( this, 'defref_srt_ConsolidatedEntitiesAxis=ions_AkceaTherapeuticsIncMember', window );">Akcea [Member] | Boston Office Space [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_LesseeDisclosureAbstract', window );"><strong>Operating Leases [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>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_LesseeOperatingLeaseRenewalTerm', window );">Term of lease extension</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></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="top.Show.showAR( this, 'defref_us-gaap_LesseeOperatingLeaseTermOfContract', window );">Term of lease</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></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 custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_LesseeOperatingLeasePeriodOfFreeRent', window );">Period of free rent under lease</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></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="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_LesseeOperatingLeaseAllowanceForTenantImprovements', window );">Tenant improvement allowance</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">$ 3,800<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_LesseeOperatingLeaseInitialLetterOfCreditToSecureLeaseObligation', window );">Initial amount of letter of credit</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">2,400<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="top.Show.showAR( this, 'defref_ions_LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnThirdAnniversaryOfRentCommencementDate', window );">Letter of credit on third anniversary of rent commencement date</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">1,800<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnFifthAnniversaryOfRentCommencementDate', window );">Letter of credit on fifth anniversary of rent commencement date</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">$ 1,200<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr><td colspan="4"></td></tr>
<tr><td colspan="4"><table class="outerFootnotes" width="100%">
<tr class="outerFootnote">
<td style="vertical-align: top; width: 12pt;" valign="top">[1]</td>
<td style="vertical-align: top;" valign="top">Included in <span style="-sec-ix-hidden:Fact_f81ca57385a04657b8ecd0f06d505159">deposits and other assets</span> on our consolidated balance sheet.</td>
</tr>
<tr class="outerFootnote">
<td style="vertical-align: top; width: 12pt;" valign="top">[2]</td>
<td style="vertical-align: top;" valign="top">Current portion of $2.0 million was included in <span style="-sec-ix-hidden:Fact_530181678e9244af8b37885d3ba85980">current portion of long-term obligations</span> on our consolidated balance sheet, with the difference included in <span style="-sec-ix-hidden:Fact_9c37cb3853f74a4f821bbe4ed37a06ba">long-term obligations</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_LesseeLeasingArrangementsOperatingLeasesNumberOfOptionsToExtendLease">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The number of options to extend the lease under the lessee's operating leasing arrangement.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_LesseeLeasingArrangementsOperatingLeasesNumberOfOptionsToExtendLease</td>
</tr>
<tr>
<td style="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_LesseeOperatingLeaseAllowanceForTenantImprovements">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Allowance for tenant improvements to the office space included in the lessee's operating lease.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_LesseeOperatingLeaseAllowanceForTenantImprovements</td>
</tr>
<tr>
<td style="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_LesseeOperatingLeaseInitialLetterOfCreditToSecureLeaseObligation">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Initial letter of credit provided to lessor to secure lease obligation under lessee's operating lease.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_LesseeOperatingLeaseInitialLetterOfCreditToSecureLeaseObligation</td>
</tr>
<tr>
<td style="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_LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnFifthAnniversaryOfRentCommencementDate">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Letter of credit provided to lessor to secure lease obligation under lessee's operating lease on the fifth anniversary of the rent commencement date.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnFifthAnniversaryOfRentCommencementDate</td>
</tr>
<tr>
<td style="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_LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnThirdAnniversaryOfRentCommencementDate">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Letter of credit provided to lessor to secure lease obligation under lessee's operating lease on the third anniversary of the rent commencement date.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnThirdAnniversaryOfRentCommencementDate</td>
</tr>
<tr>
<td style="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_LesseeOperatingLeasePeriodOfFreeRent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</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_us-gaap_LesseeDisclosureAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 842<br> -SubTopic 20<br> -Section 50<br> -Paragraph 6<br> -URI http://asc.fasb.org/extlink&amp;oid=121609121&amp;loc=SL77918701-209980<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 842<br> -SubTopic 20<br> -Section 50<br> -Paragraph 6<br> -URI http://asc.fasb.org/extlink&amp;oid=121609121&amp;loc=SL77918701-209980<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 842<br> -SubTopic 20<br> -Section 50<br> -Paragraph 6<br> -URI http://asc.fasb.org/extlink&amp;oid=121609121&amp;loc=SL77918701-209980<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 842<br> -SubTopic 20<br> -Section 50<br> -Paragraph 6<br> -URI http://asc.fasb.org/extlink&amp;oid=121609121&amp;loc=SL77918701-209980<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 842<br> -SubTopic 20<br> -Section 50<br> -Paragraph 6<br> -URI http://asc.fasb.org/extlink&amp;oid=121609121&amp;loc=SL77918701-209980<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 842<br> -SubTopic 20<br> -Section 50<br> -Paragraph 6<br> -URI http://asc.fasb.org/extlink&amp;oid=121609121&amp;loc=SL77918701-209980<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 842<br> -SubTopic 20<br> -Section 50<br> -Paragraph 6<br> -URI http://asc.fasb.org/extlink&amp;oid=121609121&amp;loc=SL77918701-209980<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 842<br> -SubTopic 20<br> -Section 50<br> -Paragraph 6<br> -URI http://asc.fasb.org/extlink&amp;oid=121609121&amp;loc=SL77918701-209980<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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_LesseeOperatingLeaseRenewalTerm">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 842<br> -SubTopic 20<br> -Section 50<br> -Paragraph 3<br> -Subparagraph (a)(3)<br> -URI http://asc.fasb.org/extlink&amp;oid=121609121&amp;loc=SL77918673-209980<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 842<br> -SubTopic 20<br> -Section 50<br> -Paragraph 3<br> -Subparagraph (a)(3)<br> -URI http://asc.fasb.org/extlink&amp;oid=121609121&amp;loc=SL77918673-209980<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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_OperatingLeaseExpense">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of operating lease expense. Excludes sublease income.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 842<br> -SubTopic 20<br> -Section 45<br> -Paragraph 4<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=121603541&amp;loc=SL77918638-209977<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_OperatingLeaseExpense</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_OperatingLeaseLiabilitiesPaymentsDueAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_OperatingLeaseLiabilitiesPaymentsDueAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_OperatingLeaseLiability">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 842<br> -SubTopic 20<br> -Section 45<br> -Paragraph 1<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=121603541&amp;loc=SL77918627-209977<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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_OperatingLeaseLiabilityCurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 842<br> -SubTopic 20<br> -Section 45<br> -Paragraph 1<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=121603541&amp;loc=SL77918627-209977<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_OperatingLeaseLiabilityCurrent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_OperatingLeaseLiabilityCurrentStatementOfFinancialPositionExtensibleList">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 842<br> -SubTopic 20<br> -Section 45<br> -Paragraph 2<br> -URI http://asc.fasb.org/extlink&amp;oid=121603541&amp;loc=SL77918631-209977<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_OperatingLeaseLiabilityCurrentStatementOfFinancialPositionExtensibleList</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>srt-types:extensibleListItemType</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_OperatingLeaseLiabilityNoncurrentStatementOfFinancialPositionExtensibleList">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Indicates line item in statement of financial position that includes noncurrent operating lease liability.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 842<br> -SubTopic 20<br> -Section 45<br> -Paragraph 2<br> -URI http://asc.fasb.org/extlink&amp;oid=121603541&amp;loc=SL77918631-209977<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_OperatingLeaseLiabilityNoncurrentStatementOfFinancialPositionExtensibleList</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>srt-types:extensibleListItemType</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_OperatingLeasePayments">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 842<br> -SubTopic 20<br> -Section 45<br> -Paragraph 5<br> -Subparagraph (c)<br> -URI http://asc.fasb.org/extlink&amp;oid=121603541&amp;loc=SL77918643-209977<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 842<br> -SubTopic 20<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (g)(1)<br> -URI http://asc.fasb.org/extlink&amp;oid=121609121&amp;loc=SL77918686-209980<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 842<br> -SubTopic 20<br> -Section 45<br> -Paragraph 1<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=121603541&amp;loc=SL77918627-209977<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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_OperatingLeaseRightOfUseAssetStatementOfFinancialPositionExtensibleList">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Indicates line item in statement of financial position that includes operating lease right-of-use asset.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 842<br> -SubTopic 20<br> -Section 45<br> -Paragraph 2<br> -URI http://asc.fasb.org/extlink&amp;oid=121603541&amp;loc=SL77918631-209977<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_OperatingLeaseRightOfUseAssetStatementOfFinancialPositionExtensibleList</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>srt-types:extensibleListItemType</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_OperatingLeaseWeightedAverageDiscountRatePercent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 842<br> -SubTopic 20<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (g)(4)<br> -URI http://asc.fasb.org/extlink&amp;oid=121609121&amp;loc=SL77918686-209980<br><br>Reference 2: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 842<br> -SubTopic 20<br> -Section 55<br> -Paragraph 53<br> -URI http://asc.fasb.org/extlink&amp;oid=121568110&amp;loc=SL77918982-209971<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>num: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>
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<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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 842<br> -SubTopic 20<br> -Section 55<br> -Paragraph 53<br> -URI http://asc.fasb.org/extlink&amp;oid=121568110&amp;loc=SL77918982-209971<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 842<br> -SubTopic 20<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (g)(3)<br> -URI http://asc.fasb.org/extlink&amp;oid=121609121&amp;loc=SL77918686-209980<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>
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<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
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<td>xbrli:durationItemType</td>
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<td><strong> Balance Type:</strong></td>
<td>na</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_GeographicDistributionAxis=ions_CarlsbadFacilityMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
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<a href="javascript:void(0);" onclick="top.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_GeographicDistributionAxis=ions_CarlsbadFacilityMember</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="top.Show.hideAR();">X</a></td></tr>
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<a href="javascript:void(0);" onclick="top.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_GeographicDistributionAxis=ions_CarlsbadOfficeSpacesMember</td>
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<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 class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
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<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">srt_ConsolidatedEntitiesAxis=ions_AkceaTherapeuticsIncMember</td>
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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 class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
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<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_GeographicDistributionAxis=ions_BostonOfficeSpaceMember</td>
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<head>
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<span style="display: none;">v3.20.4</span><table class="report" border="0" cellspacing="2" id="idm140142740744296">
<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, 2020</div></th>
<th class="th"><div>Dec. 31, 2019</div></th>
<th class="th"><div>Dec. 31, 2018</div></th>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="top.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="top.Show.showAR( this, 'defref_us-gaap_CommonStockSharesIssued', window );">Common stock, shares issued (in shares)</a></td>
<td class="nump">140,365,594<span></span>
</td>
<td class="nump">140,339,615<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_CommonStockSharesOutstanding', window );">Common stock, shares outstanding (in shares)</a></td>
<td class="nump">140,365,594<span></span>
</td>
<td class="nump">140,339,615<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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">$ 52,036<span></span>
</td>
<td class="nump">$ 119,657<span></span>
</td>
<td class="nump">$ 27,900<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="top.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="top.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="top.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="top.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="top.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="top.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="top.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>
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<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="top.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="top.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="top.Show.showAR( this, 'defref_us-gaap_CommonStockSharesIssued', window );">Common stock, shares issued (in shares)</a></td>
<td class="nump">140,400,000<span></span>
</td>
<td class="nump">140,300,000<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="top.Show.showAR( this, 'defref_us-gaap_CommonStockSharesOutstanding', window );">Common stock, shares outstanding (in shares)</a></td>
<td class="nump">140,400,000<span></span>
</td>
<td class="nump">140,300,000<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="top.Show.showAR( this, 'defref_us-gaap_CommonStockCapitalSharesReservedForFutureIssuance', window );">Common shares reserved for future issuance (in shares)</a></td>
<td class="nump">26,100,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensationGross', window );">Number of shares issued for stock option exercises, vesting of restricted stock units, and ESPP purchases (in shares)</a></td>
<td class="nump">1,700,000<span></span>
</td>
<td class="nump">3,100,000<span></span>
</td>
<td class="nump">1,500,000<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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">$ 52,000<span></span>
</td>
<td class="nump">$ 119,700<span></span>
</td>
<td class="nump">$ 27,900<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_CommonStockCapitalSharesReservedForFutureIssuance">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Aggregate number of common shares reserved for future issuance.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02.29)<br> -URI http://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>
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<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="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>
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<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(29))<br> -URI http://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_CommonStockSharesAuthorized</td>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(29))<br> -URI http://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_CommonStockSharesIssued</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:sharesItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_CommonStockSharesOutstanding">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 505<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -URI http://asc.fasb.org/extlink&amp;oid=109259400&amp;loc=d3e21463-112644<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(29))<br> -URI http://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>
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<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_PreferredStockNumberOfSharesParValueAndOtherDisclosuresAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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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<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(28))<br> -URI http://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PreferredStockSharesAuthorized</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
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<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:sharesItemType</td>
</tr>
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<td><strong> Balance Type:</strong></td>
<td>na</td>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_PreferredStockSharesIssued">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(28))<br> -URI http://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PreferredStockSharesIssued</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
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<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:sharesItemType</td>
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<td><strong> Balance Type:</strong></td>
<td>na</td>
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<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
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</table></div>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(28))<br> -URI http://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PreferredStockSharesOutstanding</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
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<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:sharesItemType</td>
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<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
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<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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2A<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=120381028&amp;loc=SL79508275-113901<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 14<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=121586364&amp;loc=d3e3255-108585<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>
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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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<td><strong> Period Type:</strong></td>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.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>na</td>
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<td>duration</td>
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<span style="display: none;">v3.20.4</span><table class="report" border="0" cellspacing="2" id="idm140142726595336">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Stockholders' Equity, Share Repurchase Program (Details) - USD ($)<br> $ in Thousands</strong></div></th>
<th class="th" colspan="1">3 Months Ended</th>
<th class="th" colspan="3">12 Months Ended</th>
<th class="th" colspan="1"></th>
</tr>
<tr>
<th class="th"><div>Mar. 31, 2020</div></th>
<th class="th"><div>Dec. 31, 2020</div></th>
<th class="th"><div>Dec. 31, 2019</div></th>
<th class="th"><div>Dec. 31, 2018</div></th>
<th class="th"><div>Sep. 30, 2019</div></th>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ClassOfStockDisclosuresAbstract', window );"><strong>Share Repurchase Program [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_StockRepurchaseProgramAuthorizedAmount1', window );">Authorized amount of share repurchase program</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 125,000<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_StockRepurchasedDuringPeriodShares', window );">Shares repurchased (in shares)</a></td>
<td class="nump">1,500,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">535,000<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="top.Show.showAR( this, 'defref_us-gaap_PaymentsForRepurchaseOfCommonStock', window );">Shares repurchased</a></td>
<td class="nump">$ 90,500<span></span>
</td>
<td class="nump">$ 90,548<span></span>
</td>
<td class="nump">$ 34,392<span></span>
</td>
<td class="nump">$ 0<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
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<div style="display: none;">
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<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ClassOfStockDisclosuresAbstract</td>
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<td><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="top.Show.toggleNext( this );">- Definition</a><div><p>The cash outflow to reacquire common stock during the period.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 15<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=121586364&amp;loc=d3e3291-108585<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PaymentsForRepurchaseOfCommonStock</td>
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<td><strong> Balance Type:</strong></td>
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<td><strong> Period Type:</strong></td>
<td>duration</td>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of stock repurchase plan authorized.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_StockRepurchaseProgramAuthorizedAmount1</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><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_StockRepurchasedDuringPeriodShares">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
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<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Number of shares that have been repurchased during the period and have not been retired and are not held in treasury. Some state laws may govern the circumstances under which an entity may acquire its own stock and prescribe the accounting treatment therefore. This element is used when state law does not recognize treasury stock.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 505<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -URI http://asc.fasb.org/extlink&amp;oid=109259400&amp;loc=d3e21463-112644<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(29))<br> -URI http://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 505<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.3-04)<br> -URI http://asc.fasb.org/extlink&amp;oid=120397183&amp;loc=d3e187085-122770<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(28))<br> -URI http://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_StockRepurchasedDuringPeriodShares</td>
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<td><strong> Period Type:</strong></td>
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<span style="display: none;">v3.20.4</span><table class="report" border="0" cellspacing="2" id="idm140142741220536">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Stockholders' Equity, Stock Plans (Details)<br></strong></div></th>
<th class="th" colspan="1">1 Months Ended</th>
<th class="th" colspan="1">12 Months Ended</th>
<th class="th" colspan="1"></th>
<th class="th" colspan="1"></th>
<th class="th" colspan="1"></th>
<th class="th" colspan="1"></th>
<th class="th" colspan="1"></th>
<th class="th" colspan="1"></th>
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<tr>
<th class="th">
<div>Jun. 30, 2009 </div>
<div>shares</div>
</th>
<th class="th">
<div>Dec. 31, 2020 </div>
<div>Officer </div>
<div>$ / shares </div>
<div>shares</div>
</th>
<th class="th">
<div>Jun. 30, 2020 </div>
<div>shares</div>
</th>
<th class="th">
<div>Dec. 31, 2019 </div>
<div>shares</div>
</th>
<th class="th">
<div>Jun. 30, 2019 </div>
<div>shares</div>
</th>
<th class="th">
<div>May 31, 2017 </div>
<div>shares</div>
</th>
<th class="th">
<div>Jun. 30, 2015 </div>
<div>shares</div>
</th>
<th class="th">
<div>May 31, 2015 </div>
<div>shares</div>
</th>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AwardTypeAxis=us-gaap_StockOptionMember', window );">Stock Options [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber', window );">Number of options outstanding (in shares)</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">12,335,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">11,001,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisableNumber', window );">Number of options exercisable (in shares)</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">7,366,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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="top.Show.showAR( this, 'defref_us-gaap_AwardTypeAxis=us-gaap_RestrictedStockUnitsRSUMember', window );">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>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1', window );">Vesting period</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">4 years<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAuthorized', window );">Number of shares authorized (in shares)</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">20,000,000.0<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>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber', window );">Number of options outstanding (in shares)</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">30,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisableNumber', window );">Number of options exercisable (in shares)</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">30,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAvailableForGrant', window );">Number of shares available for grant (in shares)</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">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>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1', window );">Vesting period</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">4 years<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod', window );">Award term</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">7 years<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage', window );">Vesting percentage</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">25.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardRequisiteServicePeriod1', window );">Period before options are exercisable</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">1 year<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAuthorized', window );">Number of shares authorized (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="nump">23,000,000.0<span></span>
</td>
<td class="nump">16,000,000.0<span></span>
</td>
<td class="nump">11,000,000.0<span></span>
</td>
<td class="nump">5,500,000<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber', window );">Number of options outstanding (in shares)</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">11,400,000<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>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisableNumber', window );">Number of options exercisable (in shares)</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">6,700,000<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>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAvailableForGrant', window );">Number of shares available for grant (in shares)</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">4,300,000<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>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_NumberOfExecutiveOfficersTerminatedBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers', window );">Number of executive officers terminated before change in control when vesting will accelerate for executive officers | Officer</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">1<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_PeriodBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers', window );">Period before change in control when vesting will accelerate for executive officers</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">3 months<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_PeriodAfterChangeInControlWhenVestingWillAccelerateForExecutiveOfficers', window );">Period after change in control when vesting will accelerate for executive officers</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">12 months<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_PlanNameAxis=ions_EquityIncentivePlan2011Member', window );">2011 Equity Incentive Plan [Member] | Restricted Stock Units [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1', window );">Vesting period</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">4 years<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNonOptionEquityInstrumentsOutstandingNumber', window );">Number of awards outstanding (in shares)</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">2,200,000<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>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAuthorized', window );">Number of shares authorized (in shares)</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">2,600,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber', window );">Number of options outstanding (in shares)</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">10,000.00<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>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisableNumber', window );">Number of options exercisable (in shares)</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">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>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAvailableForGrant', window );">Number of shares available for grant (in shares)</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">2,600,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_PlanNameAxis=ions_EquityIncentivePlan2020Member', window );">2020 Equity Incentive Plan [Member] | Stock Options [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1', window );">Vesting period</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">4 years<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_PlanNameAxis=ions_NonemployeeDirectorsStockOptionPlan2002Member', window );">2002 Non-Employee Directors' Stock Option Plan [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAuthorized', window );">Number of shares authorized (in shares)</a></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="nump">2,000,000.0<span></span>
</td>
<td class="nump">1,200,000<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber', window );">Number of options outstanding (in shares)</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">1,000,000.0<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>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisableNumber', window );">Number of options exercisable (in shares)</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">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>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAvailableForGrant', window );">Number of shares available for grant (in shares)</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">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>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod', window );">Award term</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">10 years<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNonOptionEquityInstrumentsOutstandingNumber', window );">Number of awards outstanding (in shares)</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">100,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAuthorized', window );">Number of shares authorized (in shares)</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">3,200,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfAdditionalSharesAuthorized', window );">Number of additional shares reserved for issuance (in shares)</a></td>
<td class="nump">150,000<span></span>
</td>
<td class="nump">150,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardMaximumEmployeeSubscriptionRate', window );">Maximum percentage of employee compensation used to purchase shares</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">10.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardPurchasePriceOfCommonStockPercent', window );">Percentage of fair market value used to determine purchase price of stock</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">85.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardHoldingPeriod', window );">Holding period for purchased stock</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">6 months<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_StockIssuedDuringPeriodSharesEmployeeStockPurchasePlans', window );">Shares purchased and issued under ESPP (in shares)</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">60,000.00<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>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_EmployeeStockPurchasePlanWeightedAverageSalesPriceOfSharesPurchased', window );">Weighted average purchase price (in dollars per share) | $ / shares</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 43.65<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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="top.Show.showAR( this, 'defref_ions_EmployeeStockPurchasePlanSharesAvailableForPurchase', window );">Shares available for purchase under ESPP (in shares)</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">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>
</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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</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>num: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_NumberOfExecutiveOfficersTerminatedBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (a)(1)<br> -URI http://asc.fasb.org/extlink&amp;oid=120381028&amp;loc=d3e5070-113901<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (a)(1)<br> -URI http://asc.fasb.org/extlink&amp;oid=120381028&amp;loc=d3e5070-113901<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -URI http://asc.fasb.org/extlink&amp;oid=120381028&amp;loc=d3e5070-113901<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>num: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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)(1)(ii)<br> -URI http://asc.fasb.org/extlink&amp;oid=120381028&amp;loc=d3e5070-113901<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)(1)(i)<br> -URI http://asc.fasb.org/extlink&amp;oid=120381028&amp;loc=d3e5070-113901<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (a)(3)<br> -URI http://asc.fasb.org/extlink&amp;oid=120381028&amp;loc=d3e5070-113901<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -URI http://asc.fasb.org/extlink&amp;oid=120381028&amp;loc=d3e5070-113901<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)(1)(iii)<br> -URI http://asc.fasb.org/extlink&amp;oid=120381028&amp;loc=d3e5070-113901<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -URI http://asc.fasb.org/extlink&amp;oid=120381028&amp;loc=d3e5070-113901<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)(1)(i)-(ii)<br> -URI http://asc.fasb.org/extlink&amp;oid=120381028&amp;loc=d3e5070-113901<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (a)(1)<br> -URI http://asc.fasb.org/extlink&amp;oid=120381028&amp;loc=d3e5070-113901<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>num: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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (a)(2)<br> -URI http://asc.fasb.org/extlink&amp;oid=120381028&amp;loc=d3e5070-113901<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>num: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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 505<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -URI http://asc.fasb.org/extlink&amp;oid=109259400&amp;loc=d3e21463-112644<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 505<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.3-04)<br> -URI http://asc.fasb.org/extlink&amp;oid=120397183&amp;loc=d3e187085-122770<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(28))<br> -URI http://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(29))<br> -URI http://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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_AwardTypeAxis=us-gaap_RestrictedStockUnitsRSUMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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_StockOptionPlan1989Member">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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_PlanNameAxis=ions_EquityIncentivePlan2020Member">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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>
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<DOCUMENT>
<TYPE>XML
<SEQUENCE>99
<FILENAME>R63.htm
<DESCRIPTION>IDEA: XBRL DOCUMENT
<TEXT>
<html>
<head>
<title></title>
<link rel="stylesheet" type="text/css" href="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;">v3.20.4</span><table class="report" border="0" cellspacing="2" id="idm140142739926184">
<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, 2020</div></th>
<th class="th"><div>Dec. 31, 2019</div></th>
<th class="th"><div>Dec. 31, 2018</div></th>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="top.Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber', window );">Outstanding at beginning of period (in shares)</a></td>
<td class="nump">11,001<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodGross', window );">Granted (in shares)</a></td>
<td class="nump">2,764<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_StockIssuedDuringPeriodSharesStockOptionsExercised', window );">Exercised (in shares)</a></td>
<td class="num">(1,069)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsForfeituresAndExpirationsInPeriod', window );">Cancelled/forfeited/expired (in shares)</a></td>
<td class="num">(361)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber', window );">Outstanding at end of period (in shares)</a></td>
<td class="nump">12,335<span></span>
</td>
<td class="nump">11,001<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisableNumber', window );">Exercisable at end of period (in shares)</a></td>
<td class="nump">7,366<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="top.Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePrice', window );">Outstanding at beginning of period (in dollars per share)</a></td>
<td class="nump">$ 51.48<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageExercisePrice', window );">Granted (in dollars per share)</a></td>
<td class="nump">59.89<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardOptionsExercisesInPeriodWeightedAverageExercisePrice', window );">Exercised (in dollars per share)</a></td>
<td class="nump">40.88<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardOptionsForfeituresInPeriodWeightedAverageExercisePrice', window );">Cancelled/forfeited/expired (in dollars per share)</a></td>
<td class="nump">56.48<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePrice', window );">Outstanding at end of period (in dollars per share)</a></td>
<td class="nump">54.14<span></span>
</td>
<td class="nump">$ 51.48<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisableWeightedAverageExercisePrice', window );">Exercisable at end of period (in dollars per share)</a></td>
<td class="nump">$ 52.45<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="top.Show.showAR( this, 'defref_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsOutstandingWeightedAverageRemainingContractualTerm2', window );">Average remaining contractual term, outstanding at end of period</a></td>
<td class="text">4 years 1 month 28 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="top.Show.showAR( this, 'defref_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsExercisableWeightedAverageRemainingContractualTerm1', window );">Average remaining contractual term, exercisable at end of period</a></td>
<td class="text">3 years 1 month 28 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="top.Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingIntrinsicValue', window );">Aggregate intrinsic value, outstanding at end of period</a></td>
<td class="nump">$ 55,885<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsExercisableIntrinsicValue1', window );">Aggregate intrinsic value, exercisable at end of period</a></td>
<td class="nump">$ 43,267<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue', window );">Weighted average fair value of options granted (in dollars per share)</a></td>
<td class="nump">$ 29.43<span></span>
</td>
<td class="nump">$ 28.76<span></span>
</td>
<td class="nump">$ 25.49<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisesInPeriodTotalIntrinsicValue', window );">Intrinsic value of options exercised</a></td>
<td class="nump">$ 15,500<span></span>
</td>
<td class="nump">$ 83,800<span></span>
</td>
<td class="nump">$ 34,800<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ProceedsFromStockOptionsExercised', window );">Cash received from exercise of stock options</a></td>
<td class="nump">$ 43,700<span></span>
</td>
<td class="nump">$ 105,900<span></span>
</td>
<td class="nump">$ 18,900<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisesInPeriodWeightedAverageFairValue', window );">Weighted-average fair value of options exercised (in dollars per share)</a></td>
<td class="nump">$ 55.33<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="top.Show.showAR( this, 'defref_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedStockOptions', window );">Unrecognized compensation cost related to non-vested stock options</a></td>
<td class="nump">$ 54,100<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</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>num: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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (i)<br> -URI http://asc.fasb.org/extlink&amp;oid=120381028&amp;loc=d3e5070-113901<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (i)<br> -URI http://asc.fasb.org/extlink&amp;oid=120381028&amp;loc=d3e5070-113901<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2A<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=120381028&amp;loc=SL79508275-113901<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 14<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=121586364&amp;loc=d3e3255-108585<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)(1)(iii)<br> -URI http://asc.fasb.org/extlink&amp;oid=120381028&amp;loc=d3e5070-113901<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)(1)(iii)<br> -URI http://asc.fasb.org/extlink&amp;oid=120381028&amp;loc=d3e5070-113901<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>num: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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (d)(2)<br> -URI http://asc.fasb.org/extlink&amp;oid=120381028&amp;loc=d3e5070-113901<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)(1)(iv)(3)-(4)<br> -URI http://asc.fasb.org/extlink&amp;oid=120381028&amp;loc=d3e5070-113901<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (d)(1)<br> -URI http://asc.fasb.org/extlink&amp;oid=120381028&amp;loc=d3e5070-113901<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>num: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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -URI http://asc.fasb.org/extlink&amp;oid=120381028&amp;loc=d3e5070-113901<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -URI http://asc.fasb.org/extlink&amp;oid=120381028&amp;loc=d3e5070-113901<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)(1)(i)-(ii)<br> -URI http://asc.fasb.org/extlink&amp;oid=120381028&amp;loc=d3e5070-113901<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:sharesItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingRollForward">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingRollForward</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePrice">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)(1)(i)<br> -URI http://asc.fasb.org/extlink&amp;oid=120381028&amp;loc=d3e5070-113901<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePrice</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>num:perShareItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePriceRollforward">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePriceRollforward</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardOptionsExercisesInPeriodWeightedAverageExercisePrice">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>num:perShareItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardOptionsForfeituresInPeriodWeightedAverageExercisePrice">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardOptionsForfeituresInPeriodWeightedAverageExercisePrice</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>num:perShareItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageExercisePrice">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>num: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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -URI http://asc.fasb.org/extlink&amp;oid=120381028&amp;loc=d3e5070-113901<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsExercisableIntrinsicValue1</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsExercisableWeightedAverageRemainingContractualTerm1">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -URI http://asc.fasb.org/extlink&amp;oid=120381028&amp;loc=d3e5070-113901<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsExercisableWeightedAverageRemainingContractualTerm1</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:durationItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsOutstandingWeightedAverageRemainingContractualTerm2">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (e)(1)<br> -URI http://asc.fasb.org/extlink&amp;oid=120381028&amp;loc=d3e5070-113901<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsOutstandingWeightedAverageRemainingContractualTerm2</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:durationItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_StockIssuedDuringPeriodSharesStockOptionsExercised">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)(1)(iv)(2)<br> -URI http://asc.fasb.org/extlink&amp;oid=120381028&amp;loc=d3e5070-113901<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 505<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.3-04)<br> -URI http://asc.fasb.org/extlink&amp;oid=120397183&amp;loc=d3e187085-122770<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(28))<br> -URI http://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(29))<br> -URI http://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br><br>Reference 5: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 505<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -URI http://asc.fasb.org/extlink&amp;oid=109259400&amp;loc=d3e21463-112644<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_StockIssuedDuringPeriodSharesStockOptionsExercised</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:sharesItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AwardTypeAxis=us-gaap_StockOptionMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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>
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<span style="display: none;">v3.20.4</span><table class="report" border="0" cellspacing="2" id="idm140142728245816">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Stockholders' Equity, Restricted Stock Unit Activity (Details) - Restricted Stock Units [Member] - USD ($)<br> $ / shares in Units, shares in Thousands, $ in Millions</strong></div></th>
<th class="th" colspan="3">12 Months Ended</th>
</tr>
<tr>
<th class="th"><div>Dec. 31, 2020</div></th>
<th class="th"><div>Dec. 31, 2019</div></th>
<th class="th"><div>Dec. 31, 2018</div></th>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward', window );"><strong>Number of Shares [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber', window );">Non-vested at beginning of period (in shares)</a></td>
<td class="nump">1,866<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriod', window );">Granted (in shares)</a></td>
<td class="nump">1,244<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriod', window );">Vested (in shares)</a></td>
<td class="num">(602)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeitedInPeriod', window );">Cancelled/forfeited (in shares)</a></td>
<td class="num">(134)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber', window );">Non-vested at end of period (in shares)</a></td>
<td class="nump">2,374<span></span>
</td>
<td class="nump">1,866<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="top.Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue', window );">Non-vested at beginning of period (in dollars per share)</a></td>
<td class="nump">$ 55.80<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriodWeightedAverageGrantDateFairValue', window );">Granted (in dollars per share)</a></td>
<td class="nump">60.86<span></span>
</td>
<td class="nump">$ 60.23<span></span>
</td>
<td class="nump">$ 51.06<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriodWeightedAverageGrantDateFairValue', window );">Vested (in dollars per share)</a></td>
<td class="nump">53.68<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeituresWeightedAverageGrantDateFairValue', window );">Cancelled/forfeited (in dollars per share)</a></td>
<td class="nump">58.96<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue', window );">Non-vested at end of period (in dollars per share)</a></td>
<td class="nump">$ 58.81<span></span>
</td>
<td class="nump">$ 55.80<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="top.Show.showAR( this, 'defref_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions', window );">Unrecognized compensation cost related to non-vested RSUs</a></td>
<td class="nump">$ 55.3<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="top.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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (i)<br> -URI http://asc.fasb.org/extlink&amp;oid=120381028&amp;loc=d3e5070-113901<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (i)<br> -URI http://asc.fasb.org/extlink&amp;oid=120381028&amp;loc=d3e5070-113901<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)(1)(iv)(3)<br> -URI http://asc.fasb.org/extlink&amp;oid=120381028&amp;loc=d3e5070-113901<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)(2)(iii)(3)<br> -URI http://asc.fasb.org/extlink&amp;oid=120381028&amp;loc=d3e5070-113901<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>num: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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)(2)(iii)(1)<br> -URI http://asc.fasb.org/extlink&amp;oid=120381028&amp;loc=d3e5070-113901<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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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<td>xbrli:sharesItemType</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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)(2)(iii)(1)<br> -URI http://asc.fasb.org/extlink&amp;oid=120381028&amp;loc=d3e5070-113901<br></p></div>
<a href="javascript:void(0);" onclick="top.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_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriodWeightedAverageGrantDateFairValue</td>
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<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)(2)(i)-(ii)<br> -URI http://asc.fasb.org/extlink&amp;oid=120381028&amp;loc=d3e5070-113901<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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 class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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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<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)(2)(i)-(ii)<br> -URI http://asc.fasb.org/extlink&amp;oid=120381028&amp;loc=d3e5070-113901<br></p></div>
<a href="javascript:void(0);" onclick="top.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_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue</td>
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<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
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<tr>
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<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)(2)(iii)(2)<br> -URI http://asc.fasb.org/extlink&amp;oid=120381028&amp;loc=d3e5070-113901<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)(2)(iii)(2)<br> -URI http://asc.fasb.org/extlink&amp;oid=120381028&amp;loc=d3e5070-113901<br></p></div>
<a href="javascript:void(0);" onclick="top.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_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriodWeightedAverageGrantDateFairValue</td>
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<div>Sep. 30, 2019 </div>
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<div>Dec. 31, 2020 </div>
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<td class="nump">76,557<span></span>
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<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_IncomeStatementLocationAxis=us-gaap_SellingGeneralAndAdministrativeExpensesMember', window );">Selling, General and Administrative [Member]</a></td>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationAbstract', window );"><strong>Stock-Based Compensation [Abstract]</strong></a></td>
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<td class="nump">112,542<span></span>
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<td class="nump">50,788<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="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AllocatedShareBasedCompensationExpense', window );">Stock-based compensation expense</a></td>
<td class="num">$ (19,100)<span></span>
</td>
<td class="nump">$ 94,800<span></span>
</td>
<td class="nump">$ 37,100<span></span>
</td>
<td class="nump">$ 44,300<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions', window );">Unrecognized compensation cost related to non-vested RSUs</a></td>
<td class="text">&#160;<span></span>
</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">$ 59,300<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_NumberOfExecutiveOfficersTerminatingEmployment', window );">Number of executive officers terminating employment | Officer</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>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_NumberOfExecutiveOfficersTerminatingEmployment">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The number of executive officers terminating employment with the company.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_NumberOfExecutiveOfficersTerminatingEmployment</td>
</tr>
<tr>
<td style="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_AllocatedShareBasedCompensationExpense">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=120381028&amp;loc=d3e5047-113901<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 14.F)<br> -URI http://asc.fasb.org/extlink&amp;oid=115993241&amp;loc=d3e301413-122809<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (h)(1)(i)<br> -URI http://asc.fasb.org/extlink&amp;oid=120381028&amp;loc=d3e5070-113901<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AllocatedShareBasedCompensationExpense</td>
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<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (i)<br> -URI http://asc.fasb.org/extlink&amp;oid=120381028&amp;loc=d3e5070-113901<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>
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<td><strong> Data Type:</strong></td>
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<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_IncomeStatementLocationAxis=us-gaap_CostOfSalesMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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_CostOfSalesMember</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<td><strong> Data Type:</strong></td>
<td>na</td>
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<td><strong> Balance Type:</strong></td>
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<td><strong> Period Type:</strong></td>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_IncomeStatementLocationAxis=ions_ResearchDevelopmentAndPatentMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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=ions_ResearchDevelopmentAndPatentMember</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<td><strong> Data Type:</strong></td>
<td>na</td>
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<td><strong> Balance Type:</strong></td>
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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="top.Show.hideAR();">X</a></td></tr>
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<a href="javascript:void(0);" onclick="top.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_IncomeStatementLocationAxis=us-gaap_SellingGeneralAndAdministrativeExpensesMember</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="top.Show.hideAR();">X</a></td></tr>
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<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">srt_ConsolidatedEntitiesAxis=ions_AkceaTherapeuticsIncMember</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<td>na</td>
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<td><strong> Balance Type:</strong></td>
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<html>
<head>
<title></title>
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<span style="display: none;">v3.20.4</span><table class="report" border="0" cellspacing="2" id="idm140142740936856">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Stockholders' Equity, Stock-based Valuation Information (Details) - $ / shares<br></strong></div></th>
<th class="th" colspan="3">12 Months Ended</th>
</tr>
<tr>
<th class="th"><div>Dec. 31, 2020</div></th>
<th class="th"><div>Dec. 31, 2019</div></th>
<th class="th"><div>Dec. 31, 2018</div></th>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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>
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<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="top.Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate', window );">Risk-free interest rate</a></td>
<td class="nump">1.50%<span></span>
</td>
<td class="nump">2.30%<span></span>
</td>
<td class="nump">2.40%<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="top.Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsWeightedAverageVolatilityRate', window );">Volatility</a></td>
<td class="nump">58.60%<span></span>
</td>
<td class="nump">60.30%<span></span>
</td>
<td class="nump">63.00%<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1', window );">Expected life</a></td>
<td class="text">4 years 8 months 12 days<span></span>
</td>
<td class="text">4 years 9 months 18 days<span></span>
</td>
<td class="text">4 years 7 months 6 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="top.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>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="top.Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate', window );">Risk-free interest rate</a></td>
<td class="nump">0.50%<span></span>
</td>
<td class="nump">1.90%<span></span>
</td>
<td class="nump">2.80%<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate', window );">Dividend yield</a></td>
<td class="nump">0.00%<span></span>
</td>
<td class="nump">0.00%<span></span>
</td>
<td class="nump">0.00%<span></span>
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<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsWeightedAverageVolatilityRate', window );">Volatility</a></td>
<td class="nump">57.60%<span></span>
</td>
<td class="nump">60.70%<span></span>
</td>
<td class="nump">61.50%<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1', window );">Expected life</a></td>
<td class="text">6 years 8 months 12 days<span></span>
</td>
<td class="text">6 years 7 months 6 days<span></span>
</td>
<td class="text">6 years 7 months 6 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="top.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="top.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="top.Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate', window );">Risk-free interest rate</a></td>
<td class="nump">0.80%<span></span>
</td>
<td class="nump">2.40%<span></span>
</td>
<td class="nump">1.80%<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="top.Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsWeightedAverageVolatilityRate', window );">Volatility</a></td>
<td class="nump">47.90%<span></span>
</td>
<td class="nump">45.60%<span></span>
</td>
<td class="nump">47.30%<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AwardTypeAxis=us-gaap_RestrictedStockUnitsRSUMember', window );">RSUs [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="top.Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsAdditionalDisclosuresAbstract', window );"><strong>Akcea RSU's [Abstract]</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="top.Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriodWeightedAverageGrantDateFairValue', window );">Weighted-average grant date fair value (in dollars per share)</a></td>
<td class="nump">$ 60.86<span></span>
</td>
<td class="nump">$ 60.23<span></span>
</td>
<td class="nump">$ 51.06<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_srt_ConsolidatedEntitiesAxis=ions_AkceaTherapeuticsIncMember', window );">Akcea [Member] | 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="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="top.Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate', window );">Risk-free interest rate</a></td>
<td class="nump">1.10%<span></span>
</td>
<td class="nump">2.20%<span></span>
</td>
<td class="nump">2.80%<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsWeightedAverageVolatilityRate', window );">Volatility</a></td>
<td class="nump">75.00%<span></span>
</td>
<td class="nump">75.40%<span></span>
</td>
<td class="nump">77.10%<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1', window );">Expected life</a></td>
<td class="text">6 years 29 days<span></span>
</td>
<td class="text">6 years 1 month 2 days<span></span>
</td>
<td class="text">6 years 29 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="top.Show.showAR( this, 'defref_srt_ConsolidatedEntitiesAxis=ions_AkceaTherapeuticsIncMember', window );">Akcea [Member] | 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>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="top.Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate', window );">Risk-free interest rate</a></td>
<td class="nump">0.80%<span></span>
</td>
<td class="nump">1.80%<span></span>
</td>
<td class="nump">2.90%<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsWeightedAverageVolatilityRate', window );">Volatility</a></td>
<td class="nump">75.30%<span></span>
</td>
<td class="nump">73.80%<span></span>
</td>
<td class="nump">78.20%<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1', window );">Expected life</a></td>
<td class="text">5 years 8 months 1 day<span></span>
</td>
<td class="text">6 years 3 months<span></span>
</td>
<td class="text">6 years 5 months 1 day<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_srt_ConsolidatedEntitiesAxis=ions_AkceaTherapeuticsIncMember', window );">Akcea [Member] | 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="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="top.Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate', window );">Risk-free interest rate</a></td>
<td class="nump">1.00%<span></span>
</td>
<td class="nump">2.40%<span></span>
</td>
<td class="nump">1.90%<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsWeightedAverageVolatilityRate', window );">Volatility</a></td>
<td class="nump">71.90%<span></span>
</td>
<td class="nump">60.00%<span></span>
</td>
<td class="nump">64.20%<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_srt_ConsolidatedEntitiesAxis=ions_AkceaTherapeuticsIncMember', window );">Akcea [Member] | RSUs [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="top.Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsAdditionalDisclosuresAbstract', window );"><strong>Akcea RSU's [Abstract]</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="top.Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriodWeightedAverageGrantDateFairValue', window );">Weighted-average grant date fair value (in dollars per share)</a></td>
<td class="nump">$ 15.57<span></span>
</td>
<td class="nump">$ 21.95<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_srt_ConsolidatedEntitiesAxis=ions_AkceaTherapeuticsIncMember', window );">Akcea [Member] | RSUs [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>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsAdditionalDisclosuresAbstract', window );"><strong>Akcea RSU's [Abstract]</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="top.Show.showAR( this, 'defref_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod', window );">Award term</a></td>
<td class="text">6 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="top.Show.showAR( this, 'defref_srt_ConsolidatedEntitiesAxis=ions_AkceaTherapeuticsIncMember', window );">Akcea [Member] | RSUs [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>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsAdditionalDisclosuresAbstract', window );"><strong>Akcea RSU's [Abstract]</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="top.Show.showAR( this, 'defref_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod', window );">Award term</a></td>
<td class="text">4 years<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
</table>
<div style="display: none;">
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsAdditionalDisclosuresAbstract</td>
</tr>
<tr>
<td style="padding-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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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)(2)(iii)(1)<br> -URI http://asc.fasb.org/extlink&amp;oid=120381028&amp;loc=d3e5070-113901<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>
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<tr>
<td><strong> Data Type:</strong></td>
<td>num: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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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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</tr>
<tr>
<td><strong> Data Type:</strong></td>
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<td><strong> Balance Type:</strong></td>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (f)(2)(iii)<br> -URI http://asc.fasb.org/extlink&amp;oid=120381028&amp;loc=d3e5070-113901<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<td><strong> Data Type:</strong></td>
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<td><strong> Balance Type:</strong></td>
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</tr>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (f)(2)(iv)<br> -URI http://asc.fasb.org/extlink&amp;oid=120381028&amp;loc=d3e5070-113901<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (f)(2)(ii)<br> -URI http://asc.fasb.org/extlink&amp;oid=120381028&amp;loc=d3e5070-113901<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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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<tr>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (a)(2)<br> -URI http://asc.fasb.org/extlink&amp;oid=120381028&amp;loc=d3e5070-113901<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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><strong> Balance Type:</strong></td>
<td>na</td>
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<td><strong> Period Type:</strong></td>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (f)(2)(i)<br> -URI http://asc.fasb.org/extlink&amp;oid=120381028&amp;loc=d3e5070-113901<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 14.D.2)<br> -URI http://asc.fasb.org/extlink&amp;oid=115993241&amp;loc=d3e301413-122809<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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 style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<td><strong> Balance Type:</strong></td>
<td>na</td>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
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<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
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<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
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<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
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<td><strong> Name:</strong></td>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
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<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
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<span style="display: none;">v3.20.4</span><table class="report" border="0" cellspacing="2" id="idm140142734948504">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Income Taxes, Income (Loss) Before Income Taxes (Details) - USD ($)<br> $ in Thousands</strong></div></th>
<th class="th" colspan="3">12 Months Ended</th>
</tr>
<tr>
<th class="th"><div>Dec. 31, 2020</div></th>
<th class="th"><div>Dec. 31, 2019</div></th>
<th class="th"><div>Dec. 31, 2018</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="top.Show.showAR( this, 'defref_us-gaap_IncomeTaxDisclosureAbstract', window );"><strong>Income Taxes [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
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<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesDomestic', window );">United States</a></td>
<td class="num">$ (172,702)<span></span>
</td>
<td class="nump">$ 344,280<span></span>
</td>
<td class="num">$ (69,576)<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="top.Show.showAR( this, 'defref_us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesForeign', window );">Foreign</a></td>
<td class="nump">2,670<span></span>
</td>
<td class="nump">2,489<span></span>
</td>
<td class="num">(6,580)<span></span>
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<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesMinorityInterestAndIncomeLossFromEquityMethodInvestments', window );">Income (loss) before income tax benefit (expense)</a></td>
<td class="num">$ (170,032)<span></span>
</td>
<td class="nump">$ 346,769<span></span>
</td>
<td class="num">$ (76,156)<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesDomestic">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 235<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.4-08.(h)(1)(i))<br> -URI http://asc.fasb.org/extlink&amp;oid=120395691&amp;loc=d3e23780-122690<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 6.I.Fact.3)<br> -URI http://asc.fasb.org/extlink&amp;oid=116825942&amp;loc=d3e330036-122817<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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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<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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 235<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.4-08.(h)(1)(i))<br> -URI http://asc.fasb.org/extlink&amp;oid=120395691&amp;loc=d3e23780-122690<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 6.I.Fact.3)<br> -URI http://asc.fasb.org/extlink&amp;oid=116825942&amp;loc=d3e330036-122817<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<td><strong> Period Type:</strong></td>
<td>duration</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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of income (loss) from continuing operations before deduction of income tax expense (benefit) and income (loss) attributable to noncontrolling interest, and addition of income (loss) from equity method investments.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (f)<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e8933-108599<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (c)<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e8933-108599<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 30<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e8906-108599<br><br>Reference 4: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 31<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e8924-108599<br><br>Reference 5: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 235<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.4-08.(h)(1)(i))<br> -URI http://asc.fasb.org/extlink&amp;oid=120395691&amp;loc=d3e23780-122690<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 22<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e8736-108599<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesMinorityInterestAndIncomeLossFromEquityMethodInvestments</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>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
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<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
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<table 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="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>
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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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<span style="display: none;">v3.20.4</span><table class="report" border="0" cellspacing="2" id="idm140142736192136">
<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, 2020</div></th>
<th class="th"><div>Dec. 31, 2019</div></th>
<th class="th"><div>Dec. 31, 2018</div></th>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="top.Show.showAR( this, 'defref_us-gaap_CurrentFederalTaxExpenseBenefit', window );">Federal</a></td>
<td class="num">$ (837)<span></span>
</td>
<td class="nump">$ 35,861<span></span>
</td>
<td class="nump">$ 438<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_CurrentStateAndLocalTaxExpenseBenefit', window );">State</a></td>
<td class="nump">3,782<span></span>
</td>
<td class="nump">14,329<span></span>
</td>
<td class="num">(1,442)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_CurrentForeignTaxExpenseBenefit', window );">Foreign</a></td>
<td class="nump">518<span></span>
</td>
<td class="nump">413<span></span>
</td>
<td class="nump">374<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_CurrentIncomeTaxExpenseBenefit', window );">Total current income tax expense (benefit)</a></td>
<td class="nump">3,463<span></span>
</td>
<td class="nump">50,603<span></span>
</td>
<td class="num">(630)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="top.Show.showAR( this, 'defref_us-gaap_DeferredFederalIncomeTaxExpenseBenefit', window );">Federal</a></td>
<td class="nump">313,271<span></span>
</td>
<td class="num">(7,096)<span></span>
</td>
<td class="num">(290,511)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="top.Show.showAR( this, 'defref_us-gaap_DeferredIncomeTaxExpenseBenefit', window );">Total deferred income tax benefit</a></td>
<td class="nump">313,271<span></span>
</td>
<td class="num">(7,096)<span></span>
</td>
<td class="num">(290,511)<span></span>
</td>
</tr>
<tr class="rou">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_IncomeTaxExpenseBenefit', window );">Total income tax expense (benefit)</a></td>
<td class="nump">$ 316,734<span></span>
</td>
<td class="nump">$ 43,507<span></span>
</td>
<td class="num">$ (291,141)<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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of current federal tax expense (benefit) pertaining to income (loss) from continuing operations.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 6.I.7)<br> -URI http://asc.fasb.org/extlink&amp;oid=116825942&amp;loc=d3e330036-122817<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 235<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.4-08(h))<br> -URI http://asc.fasb.org/extlink&amp;oid=120395691&amp;loc=d3e23780-122690<br><br>Reference 3: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 9<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=84230637&amp;loc=d3e32639-109319<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>
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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>
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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_CurrentForeignTaxExpenseBenefit">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 9<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=84230637&amp;loc=d3e32639-109319<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 235<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.4-08.(h))<br> -URI http://asc.fasb.org/extlink&amp;oid=120395691&amp;loc=d3e23780-122690<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>
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<td><strong> Balance Type:</strong></td>
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<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
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<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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 6.I.7)<br> -URI http://asc.fasb.org/extlink&amp;oid=116825942&amp;loc=d3e330036-122817<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 9<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=84230637&amp;loc=d3e32639-109319<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 6.I.Fact.2)<br> -URI http://asc.fasb.org/extlink&amp;oid=116825942&amp;loc=d3e330036-122817<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 235<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.4-08(h))<br> -URI http://asc.fasb.org/extlink&amp;oid=120395691&amp;loc=d3e23780-122690<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_CurrentIncomeTaxExpenseBenefit</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
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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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>
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<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
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<td><strong> Balance Type:</strong></td>
<td>na</td>
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<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
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</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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of current state and local tax expense (benefit) pertaining to income (loss) from continuing operations.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 235<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.4-08(h))<br> -URI http://asc.fasb.org/extlink&amp;oid=120395691&amp;loc=d3e23780-122690<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 6.I.7)<br> -URI http://asc.fasb.org/extlink&amp;oid=116825942&amp;loc=d3e330036-122817<br><br>Reference 3: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 9<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=84230637&amp;loc=d3e32639-109319<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_CurrentStateAndLocalTaxExpenseBenefit</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
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<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
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<td><strong> Period Type:</strong></td>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of deferred federal income tax expense (benefit) pertaining to income (loss) from continuing operations.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 235<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.4-08(h))<br> -URI http://asc.fasb.org/extlink&amp;oid=120395691&amp;loc=d3e23780-122690<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 6.I.7)<br> -URI http://asc.fasb.org/extlink&amp;oid=116825942&amp;loc=d3e330036-122817<br><br>Reference 3: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 9<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=84230637&amp;loc=d3e32639-109319<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
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<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
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<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
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<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 6.I.7)<br> -URI http://asc.fasb.org/extlink&amp;oid=116825942&amp;loc=d3e330036-122817<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 6.I.Fact.1)<br> -URI http://asc.fasb.org/extlink&amp;oid=116825942&amp;loc=d3e330036-122817<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 235<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.4-08(h))<br> -URI http://asc.fasb.org/extlink&amp;oid=120395691&amp;loc=d3e23780-122690<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 6.I.Fact.2)<br> -URI http://asc.fasb.org/extlink&amp;oid=116825942&amp;loc=d3e330036-122817<br><br>Reference 5: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=121586364&amp;loc=d3e3602-108585<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 9<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=84230637&amp;loc=d3e32639-109319<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>
</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>
</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="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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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<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_DeferredStateAndLocalIncomeTaxExpenseBenefit">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of deferred state and local tax expense (benefit) pertaining to income (loss) from continuing operations.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 9<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=84230637&amp;loc=d3e32639-109319<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 6.I.7)<br> -URI http://asc.fasb.org/extlink&amp;oid=116825942&amp;loc=d3e330036-122817<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 235<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.4-08(h))<br> -URI http://asc.fasb.org/extlink&amp;oid=120395691&amp;loc=d3e23780-122690<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>
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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>debit</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="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB TOPIC 6.I.7)<br> -URI http://asc.fasb.org/extlink&amp;oid=116825942&amp;loc=d3e330036-122817<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 10<br> -URI http://asc.fasb.org/extlink&amp;oid=84230637&amp;loc=d3e32672-109319<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 22<br> -Subparagraph (h)<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e8736-108599<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 235<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.4-08(h))<br> -URI http://asc.fasb.org/extlink&amp;oid=120395691&amp;loc=d3e23780-122690<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 250<br> -SubTopic 10<br> -Section 50<br> -Paragraph 9<br> -URI http://asc.fasb.org/extlink&amp;oid=109234566&amp;loc=d3e22663-107794<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 20<br> -Section 45<br> -Paragraph 2<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=120385591&amp;loc=d3e38679-109324<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 944<br> -SubTopic 220<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-04(9))<br> -URI http://asc.fasb.org/extlink&amp;oid=120400993&amp;loc=SL114874131-224263<br><br>Reference 8: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 250<br> -SubTopic 10<br> -Section 50<br> -Paragraph 8<br> -URI http://asc.fasb.org/extlink&amp;oid=109234566&amp;loc=d3e22658-107794<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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><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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<span style="display: none;">v3.20.4</span><table class="report" border="0" cellspacing="2" id="idm140142740691112">
<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, 2020</div></th>
<th class="th"><div>Dec. 31, 2019</div></th>
<th class="th"><div>Dec. 31, 2018</div></th>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="top.Show.showAR( this, 'defref_us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesMinorityInterestAndIncomeLossFromEquityMethodInvestments', window );">Pre-tax income (loss)</a></td>
<td class="num">$ (170,032)<span></span>
</td>
<td class="nump">$ 346,769<span></span>
</td>
<td class="num">$ (76,156)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_IncomeTaxReconciliationIncomeTaxExpenseBenefitAtFederalStatutoryIncomeTaxRate', window );">Statutory rate</a></td>
<td class="num">(35,707)<span></span>
</td>
<td class="nump">72,822<span></span>
</td>
<td class="num">(15,993)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_IncomeTaxReconciliationStateAndLocalIncomeTaxes', window );">State income tax net of federal benefit</a></td>
<td class="num">(39,230)<span></span>
</td>
<td class="nump">49,119<span></span>
</td>
<td class="num">(2,202)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_IncomeTaxReconciliationForeignIncomeTaxRateDifferential', window );">Foreign</a></td>
<td class="nump">49<span></span>
</td>
<td class="nump">340<span></span>
</td>
<td class="nump">1,735<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_IncomeTaxReconciliationChangeInDeferredTaxAssetsValuationAllowance', window );">Net change in valuation allowance</a></td>
<td class="nump">437,597<span></span>
</td>
<td class="num">(37,765)<span></span>
</td>
<td class="num">(277,924)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_EffectiveIncomeTaxRateReconciliationExpirationOfNetOperatingLossAmount', window );">Net operating loss expiration</a></td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">8,864<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_EffectiveIncomeTaxRateReconciliationDrugLicensingGainAmount', window );">TEGSEDI licensing gain</a></td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">59,583<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_EffectiveIncomeTaxRateReconciliationImpactFromOutsideBasisDifferencesAmount', window );">Impact from outside basis differences</a></td>
<td class="nump">0<span></span>
</td>
<td class="num">(16,344)<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="top.Show.showAR( this, 'defref_us-gaap_IncomeTaxReconciliationTaxCredits', window );">Tax credits</a></td>
<td class="num">(18,774)<span></span>
</td>
<td class="num">(22,296)<span></span>
</td>
<td class="num">(73,362)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_IncomeTaxReconciliationPriorYearIncomeTaxes', window );">Deferred tax true-up</a></td>
<td class="num">(206)<span></span>
</td>
<td class="nump">646<span></span>
</td>
<td class="nump">9,947<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_IncomeTaxReconciliationChangeInEnactedTaxRate', window );">Tax rate change</a></td>
<td class="num">(29,131)<span></span>
</td>
<td class="nump">1,811<span></span>
</td>
<td class="num">(1,808)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_EffectiveIncomeTaxRateReconciliationNondeductibleExpenseExcessCompensationAmount', window );">Non-deductible compensation</a></td>
<td class="nump">7,931<span></span>
</td>
<td class="nump">3,361<span></span>
</td>
<td class="nump">3,154<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_IncomeTaxReconciliationNondeductibleExpenseOther', window );">Other non-deductible items</a></td>
<td class="nump">193<span></span>
</td>
<td class="nump">329<span></span>
</td>
<td class="num">(569)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_IncomeTaxReconciliationNondeductibleExpenseShareBasedCompensationCost', window );">Stock-based compensation</a></td>
<td class="nump">17,435<span></span>
</td>
<td class="num">(4,837)<span></span>
</td>
<td class="num">(4,199)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_EffectiveIncomeTaxRateReconciliationForeignDerivedIntangibleIncomeBenefitAmount', window );">Foreign-derived intangible income benefit</a></td>
<td class="nump">0<span></span>
</td>
<td class="num">(2,071)<span></span>
</td>
<td class="nump">0<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="top.Show.showAR( this, 'defref_ions_EffectiveIncomeTaxRateReconciliationAcquisitionOfNoncontrollingInterestAmount', window );">Impacts from Akcea Acquisition</a></td>
<td class="num">(22,032)<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="top.Show.showAR( this, 'defref_us-gaap_IncomeTaxReconciliationOtherAdjustments', window );">Other</a></td>
<td class="num">(1,391)<span></span>
</td>
<td class="num">(1,608)<span></span>
</td>
<td class="nump">1,633<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_IncomeTaxExpenseBenefit', window );">Total income tax expense (benefit)</a></td>
<td class="nump">$ 316,734<span></span>
</td>
<td class="nump">$ 43,507<span></span>
</td>
<td class="num">$ (291,141)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_EffectiveIncomeTaxRateReconciliationStateAndLocalIncomeTaxes', window );">State income tax net of federal benefit</a></td>
<td class="nump">23.10%<span></span>
</td>
<td class="nump">14.20%<span></span>
</td>
<td class="nump">2.90%<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_EffectiveIncomeTaxRateReconciliationForeignIncomeTaxRateDifferential', window );">Foreign</a></td>
<td class="nump">0.00%<span></span>
</td>
<td class="nump">0.10%<span></span>
</td>
<td class="num">(2.30%)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_EffectiveIncomeTaxRateReconciliationChangeInDeferredTaxAssetsValuationAllowance', window );">Net change in valuation allowance</a></td>
<td class="num">(257.40%)<span></span>
</td>
<td class="num">(10.90%)<span></span>
</td>
<td class="nump">364.90%<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_EffectiveIncomeTaxRateReconciliationExpirationOfNetOperatingLossPercent', window );">Net operating loss expiration</a></td>
<td class="nump">0.00%<span></span>
</td>
<td class="nump">0.00%<span></span>
</td>
<td class="num">(11.60%)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_EffectiveIncomeTaxRateReconciliationDrugLicensingGainPercent', window );">TEGSEDI licensing gain</a></td>
<td class="nump">0.00%<span></span>
</td>
<td class="nump">0.00%<span></span>
</td>
<td class="num">(78.20%)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_EffectiveIncomeTaxRateReconciliationImpactFromOutsideBasisDifferencesPercent', window );">Impact from outside basis differences</a></td>
<td class="nump">0.00%<span></span>
</td>
<td class="num">(4.70%)<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="top.Show.showAR( this, 'defref_us-gaap_EffectiveIncomeTaxRateReconciliationTaxCredits', window );">Tax credits</a></td>
<td class="nump">11.00%<span></span>
</td>
<td class="num">(6.40%)<span></span>
</td>
<td class="nump">96.30%<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_EffectiveIncomeTaxRateReconciliationPriorYearIncomeTaxes', window );">Deferred tax true-up</a></td>
<td class="nump">0.10%<span></span>
</td>
<td class="nump">0.20%<span></span>
</td>
<td class="num">(13.10%)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_EffectiveIncomeTaxRateReconciliationChangeInEnactedTaxRate', window );">Tax rate change</a></td>
<td class="nump">17.10%<span></span>
</td>
<td class="nump">0.50%<span></span>
</td>
<td class="nump">2.40%<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_EffectiveIncomeTaxRateReconciliationNondeductibleExpenseExcessCompensationPercent', window );">Non-deductible compensation</a></td>
<td class="num">(4.70%)<span></span>
</td>
<td class="nump">1.00%<span></span>
</td>
<td class="num">(4.10%)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_EffectiveIncomeTaxRateReconciliationNondeductibleExpenseOther', window );">Other nondeductible items</a></td>
<td class="num">(0.10%)<span></span>
</td>
<td class="nump">0.10%<span></span>
</td>
<td class="nump">0.70%<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_EffectiveIncomeTaxRateReconciliationNondeductibleExpenseShareBasedCompensationCost', window );">Stock-based compensation</a></td>
<td class="num">(10.30%)<span></span>
</td>
<td class="num">(1.40%)<span></span>
</td>
<td class="nump">5.50%<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_EffectiveIncomeTaxRateReconciliationForeignDerivedIntangibleIncomeBenefitPercent', window );">Foreign-derived intangible income benefit</a></td>
<td class="nump">0.00%<span></span>
</td>
<td class="num">(0.60%)<span></span>
</td>
<td class="nump">0.00%<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="top.Show.showAR( this, 'defref_ions_EffectiveIncomeTaxRateReconciliationAcquisitionOfNoncontrollingInterestPercent', window );">Impacts from Akcea Acquisition</a></td>
<td class="nump">13.00%<span></span>
</td>
<td class="nump">0.00%<span></span>
</td>
<td class="nump">0.00%<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_EffectiveIncomeTaxRateReconciliationOtherAdjustments', window );">Other</a></td>
<td class="nump">0.80%<span></span>
</td>
<td class="num">(0.50%)<span></span>
</td>
<td class="num">(2.10%)<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_EffectiveIncomeTaxRateContinuingOperations', window );">Effective rate</a></td>
<td class="num">(186.40%)<span></span>
</td>
<td class="nump">12.60%<span></span>
</td>
<td class="nump">382.30%<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_EffectiveIncomeTaxRateReconciliationAcquisitionOfNoncontrollingInterestAmount">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of the difference between reported income tax expense (benefit) and expected income tax expense (benefit) computed by applying the domestic federal statutory income tax rates to pretax income (loss) from continuing operations attributable to acquisition of noncontrolling interest.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_EffectiveIncomeTaxRateReconciliationAcquisitionOfNoncontrollingInterestAmount</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_EffectiveIncomeTaxRateReconciliationAcquisitionOfNoncontrollingInterestPercent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Percentage of the difference between reported income tax expense (benefit) and expected income tax expense (benefit) computed by applying the domestic federal statutory income tax rates to pretax income (loss) from continuing operations attributable to acquisition of noncontrolling interest.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_EffectiveIncomeTaxRateReconciliationAcquisitionOfNoncontrollingInterestPercent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>num: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_EffectiveIncomeTaxRateReconciliationDrugLicensingGainAmount">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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 licensing gain on TEGSEDI.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_EffectiveIncomeTaxRateReconciliationDrugLicensingGainAmount</td>
</tr>
<tr>
<td style="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_EffectiveIncomeTaxRateReconciliationDrugLicensingGainPercent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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 licensing gain on TEGSEDI.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_EffectiveIncomeTaxRateReconciliationDrugLicensingGainPercent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>num: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_EffectiveIncomeTaxRateReconciliationExpirationOfNetOperatingLossAmount">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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 the expiration of net operating loss carryforwards.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_EffectiveIncomeTaxRateReconciliationExpirationOfNetOperatingLossAmount</td>
</tr>
<tr>
<td style="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_EffectiveIncomeTaxRateReconciliationExpirationOfNetOperatingLossPercent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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 the expiration of net operating loss carryforwards.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_EffectiveIncomeTaxRateReconciliationExpirationOfNetOperatingLossPercent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>num: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_EffectiveIncomeTaxRateReconciliationForeignDerivedIntangibleIncomeBenefitAmount">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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-derived intangible income benefit.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_EffectiveIncomeTaxRateReconciliationForeignDerivedIntangibleIncomeBenefitAmount</td>
</tr>
<tr>
<td style="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_EffectiveIncomeTaxRateReconciliationForeignDerivedIntangibleIncomeBenefitPercent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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 foreign-derived intangible income benefit.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_EffectiveIncomeTaxRateReconciliationForeignDerivedIntangibleIncomeBenefitPercent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>num: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_EffectiveIncomeTaxRateReconciliationImpactFromOutsideBasisDifferencesAmount">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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 the impact from outside basis differences.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_EffectiveIncomeTaxRateReconciliationImpactFromOutsideBasisDifferencesAmount</td>
</tr>
<tr>
<td style="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_EffectiveIncomeTaxRateReconciliationImpactFromOutsideBasisDifferencesPercent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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 the impact from outside basis differences.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_EffectiveIncomeTaxRateReconciliationImpactFromOutsideBasisDifferencesPercent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
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<td><strong> Data Type:</strong></td>
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<td><strong> Period Type:</strong></td>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_EffectiveIncomeTaxRateReconciliationNondeductibleExpenseExcessCompensationAmount">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</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>
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<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
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<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
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</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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</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>num:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
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<td><strong> Period Type:</strong></td>
<td>duration</td>
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</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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 12<br> -URI http://asc.fasb.org/extlink&amp;oid=84230637&amp;loc=d3e32687-109319<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>
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<td><strong> Data Type:</strong></td>
<td>num: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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>
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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_EffectiveIncomeTaxRateReconciliationAtFederalStatutoryIncomeTaxRate">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 6.I.Fact.4)<br> -URI http://asc.fasb.org/extlink&amp;oid=116825942&amp;loc=d3e330036-122817<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 12<br> -URI http://asc.fasb.org/extlink&amp;oid=84230637&amp;loc=d3e32687-109319<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>num: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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 6.I.Fact.4)<br> -URI http://asc.fasb.org/extlink&amp;oid=116825942&amp;loc=d3e330036-122817<br><br>Reference 2: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 12<br> -URI http://asc.fasb.org/extlink&amp;oid=84230637&amp;loc=d3e32687-109319<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>num: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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 6.I.Fact.4)<br> -URI http://asc.fasb.org/extlink&amp;oid=116825942&amp;loc=d3e330036-122817<br><br>Reference 2: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 12<br> -URI http://asc.fasb.org/extlink&amp;oid=84230637&amp;loc=d3e32687-109319<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>
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<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<td>num:percentItemType</td>
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<td><strong> Balance Type:</strong></td>
<td>na</td>
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<td><strong> Period Type:</strong></td>
<td>duration</td>
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</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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 12<br> -URI http://asc.fasb.org/extlink&amp;oid=84230637&amp;loc=d3e32687-109319<br><br>Reference 2: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 6.I.Fact.4)<br> -URI http://asc.fasb.org/extlink&amp;oid=116825942&amp;loc=d3e330036-122817<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>
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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>num:percentItemType</td>
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<td><strong> Balance Type:</strong></td>
<td>na</td>
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</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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 12<br> -URI http://asc.fasb.org/extlink&amp;oid=84230637&amp;loc=d3e32687-109319<br><br>Reference 2: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 6.I.Fact.4)<br> -URI http://asc.fasb.org/extlink&amp;oid=116825942&amp;loc=d3e330036-122817<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>
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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>num: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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</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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 12<br> -URI http://asc.fasb.org/extlink&amp;oid=84230637&amp;loc=d3e32687-109319<br><br>Reference 2: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 6.I.Fact.4)<br> -URI http://asc.fasb.org/extlink&amp;oid=116825942&amp;loc=d3e330036-122817<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>num:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
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<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_EffectiveIncomeTaxRateReconciliationOtherAdjustments">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 12<br> -URI http://asc.fasb.org/extlink&amp;oid=84230637&amp;loc=d3e32687-109319<br><br>Reference 2: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 6.I.Fact.4)<br> -URI http://asc.fasb.org/extlink&amp;oid=116825942&amp;loc=d3e330036-122817<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>
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<td>num:percentItemType</td>
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<td><strong> Balance Type:</strong></td>
<td>na</td>
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<td><strong> Period Type:</strong></td>
<td>duration</td>
</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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 12<br> -URI http://asc.fasb.org/extlink&amp;oid=84230637&amp;loc=d3e32687-109319<br><br>Reference 2: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 6.I.Fact.4)<br> -URI http://asc.fasb.org/extlink&amp;oid=116825942&amp;loc=d3e330036-122817<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>num: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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 6.I.Fact.4)<br> -URI http://asc.fasb.org/extlink&amp;oid=116825942&amp;loc=d3e330036-122817<br><br>Reference 2: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 12<br> -URI http://asc.fasb.org/extlink&amp;oid=84230637&amp;loc=d3e32687-109319<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>num: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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 12<br> -URI http://asc.fasb.org/extlink&amp;oid=84230637&amp;loc=d3e32687-109319<br><br>Reference 2: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 6.I.Fact.4)<br> -URI http://asc.fasb.org/extlink&amp;oid=116825942&amp;loc=d3e330036-122817<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_EffectiveIncomeTaxRateReconciliationTaxCredits</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>num: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_IncomeLossFromContinuingOperationsBeforeIncomeTaxesMinorityInterestAndIncomeLossFromEquityMethodInvestments">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of income (loss) from continuing operations before deduction of income tax expense (benefit) and income (loss) attributable to noncontrolling interest, and addition of income (loss) from equity method investments.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (f)<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e8933-108599<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (c)<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e8933-108599<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 30<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e8906-108599<br><br>Reference 4: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 31<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e8924-108599<br><br>Reference 5: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 235<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.4-08.(h)(1)(i))<br> -URI http://asc.fasb.org/extlink&amp;oid=120395691&amp;loc=d3e23780-122690<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 22<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e8736-108599<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesMinorityInterestAndIncomeLossFromEquityMethodInvestments</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB TOPIC 6.I.7)<br> -URI http://asc.fasb.org/extlink&amp;oid=116825942&amp;loc=d3e330036-122817<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 10<br> -URI http://asc.fasb.org/extlink&amp;oid=84230637&amp;loc=d3e32672-109319<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 22<br> -Subparagraph (h)<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e8736-108599<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 235<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.4-08(h))<br> -URI http://asc.fasb.org/extlink&amp;oid=120395691&amp;loc=d3e23780-122690<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 250<br> -SubTopic 10<br> -Section 50<br> -Paragraph 9<br> -URI http://asc.fasb.org/extlink&amp;oid=109234566&amp;loc=d3e22663-107794<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 20<br> -Section 45<br> -Paragraph 2<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=120385591&amp;loc=d3e38679-109324<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 944<br> -SubTopic 220<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-04(9))<br> -URI http://asc.fasb.org/extlink&amp;oid=120400993&amp;loc=SL114874131-224263<br><br>Reference 8: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 250<br> -SubTopic 10<br> -Section 50<br> -Paragraph 8<br> -URI http://asc.fasb.org/extlink&amp;oid=109234566&amp;loc=d3e22658-107794<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_IncomeTaxExpenseBenefit</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_IncomeTaxExpenseBenefitContinuingOperationsIncomeTaxReconciliationAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_IncomeTaxExpenseBenefitContinuingOperationsIncomeTaxReconciliationAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
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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_IncomeTaxReconciliationChangeInDeferredTaxAssetsValuationAllowance">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 12<br> -URI http://asc.fasb.org/extlink&amp;oid=84230637&amp;loc=d3e32687-109319<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_IncomeTaxReconciliationChangeInDeferredTaxAssetsValuationAllowance</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_IncomeTaxReconciliationChangeInEnactedTaxRate">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 45<br> -Paragraph 15<br> -URI http://asc.fasb.org/extlink&amp;oid=120406818&amp;loc=d3e32059-109318<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 12<br> -URI http://asc.fasb.org/extlink&amp;oid=84230637&amp;loc=d3e32687-109319<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 12<br> -URI http://asc.fasb.org/extlink&amp;oid=84230637&amp;loc=d3e32687-109319<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_IncomeTaxReconciliationForeignIncomeTaxRateDifferential</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_IncomeTaxReconciliationIncomeTaxExpenseBenefitAtFederalStatutoryIncomeTaxRate">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 12<br> -URI http://asc.fasb.org/extlink&amp;oid=84230637&amp;loc=d3e32687-109319<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 12<br> -URI http://asc.fasb.org/extlink&amp;oid=84230637&amp;loc=d3e32687-109319<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 12<br> -URI http://asc.fasb.org/extlink&amp;oid=84230637&amp;loc=d3e32687-109319<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 12<br> -URI http://asc.fasb.org/extlink&amp;oid=84230637&amp;loc=d3e32687-109319<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 12<br> -URI http://asc.fasb.org/extlink&amp;oid=84230637&amp;loc=d3e32687-109319<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 12<br> -URI http://asc.fasb.org/extlink&amp;oid=84230637&amp;loc=d3e32687-109319<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 12<br> -URI http://asc.fasb.org/extlink&amp;oid=84230637&amp;loc=d3e32687-109319<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_IncomeTaxReconciliationTaxCredits</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
</div>
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<span style="display: none;">v3.20.4</span><table class="report" border="0" cellspacing="2" id="idm140142735711144">
<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">3 Months Ended</th>
<th class="th" colspan="1">12 Months Ended</th>
<th class="th" colspan="1"></th>
</tr>
<tr>
<th class="th"><div>Dec. 31, 2020</div></th>
<th class="th"><div>Dec. 31, 2020</div></th>
<th class="th"><div>Dec. 31, 2019</div></th>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_DeferredTaxAssetsOperatingLossCarryforwards', window );">Net operating loss carryovers</a></td>
<td class="nump">$ 83,681<span></span>
</td>
<td class="nump">$ 83,681<span></span>
</td>
<td class="nump">$ 20,191<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_DeferredTaxAssetsTaxCreditCarryforwards', window );">Tax credits</a></td>
<td class="nump">245,746<span></span>
</td>
<td class="nump">245,746<span></span>
</td>
<td class="nump">210,455<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_DeferredTaxAssetsDeferredIncome', window );">Deferred revenue</a></td>
<td class="nump">124,452<span></span>
</td>
<td class="nump">124,452<span></span>
</td>
<td class="nump">127,763<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_DeferredTaxAssetsTaxDeferredExpenseCompensationAndBenefitsShareBasedCompensationCost', window );">Stock-based compensation</a></td>
<td class="nump">80,055<span></span>
</td>
<td class="nump">80,055<span></span>
</td>
<td class="nump">65,703<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_DeferredTaxAssetsGoodwillAndIntangibleAssets', window );">Intangible and capital assets</a></td>
<td class="nump">98,443<span></span>
</td>
<td class="nump">98,443<span></span>
</td>
<td class="nump">77,861<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_DeferredTaxAssetsOther', window );">Other</a></td>
<td class="nump">13,402<span></span>
</td>
<td class="nump">13,402<span></span>
</td>
<td class="nump">12,510<span></span>
</td>
</tr>
<tr class="rou">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_DeferredTaxAssetsGross', window );">Total deferred tax assets</a></td>
<td class="nump">645,779<span></span>
</td>
<td class="nump">645,779<span></span>
</td>
<td class="nump">514,483<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_DeferredTaxLiabilitiesFinancingArrangements', window );">Convertible debt</a></td>
<td class="num">(2,920)<span></span>
</td>
<td class="num">(2,920)<span></span>
</td>
<td class="num">(6,110)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_DeferredTaxLiabilitiesPropertyPlantAndEquipment', window );">Fixed assets</a></td>
<td class="num">(3,611)<span></span>
</td>
<td class="num">(3,611)<span></span>
</td>
<td class="num">(1,958)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_DeferredTaxLiabilitiesOther', window );">Other</a></td>
<td class="num">(5,808)<span></span>
</td>
<td class="num">(5,808)<span></span>
</td>
<td class="num">(3,884)<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="top.Show.showAR( this, 'defref_ions_DeferredTaxAssetsLiabilitiesNetBeforeValuationAllowance', window );">Net deferred tax asset</a></td>
<td class="nump">633,440<span></span>
</td>
<td class="nump">633,440<span></span>
</td>
<td class="nump">502,531<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_DeferredTaxAssetsValuationAllowance', window );">Valuation allowance</a></td>
<td class="num">(633,440)<span></span>
</td>
<td class="num">(633,440)<span></span>
</td>
<td class="num">(196,974)<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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>
<td class="nump">$ 305,557<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ValuationAllowancesAndReservesPeriodIncreaseDecrease', window );">Increase in valuation allowance</a></td>
<td class="nump">$ 313,000<span></span>
</td>
<td class="nump">$ 436,000<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_DeferredTaxAssetsLiabilitiesNetBeforeValuationAllowance">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_DeferredTaxAssetsLiabilitiesNetBeforeValuationAllowance</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DeferredTaxAssetsDeferredIncome">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 8<br> -URI http://asc.fasb.org/extlink&amp;oid=84230637&amp;loc=d3e32632-109319<br><br>Reference 2: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 6<br> -URI http://asc.fasb.org/extlink&amp;oid=84230637&amp;loc=d3e32621-109319<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=84230637&amp;loc=d3e32537-109319<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -URI http://asc.fasb.org/extlink&amp;oid=84230637&amp;loc=d3e32537-109319<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 8<br> -URI http://asc.fasb.org/extlink&amp;oid=84230637&amp;loc=d3e32632-109319<br><br>Reference 2: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 6<br> -URI http://asc.fasb.org/extlink&amp;oid=84230637&amp;loc=d3e32621-109319<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 6<br> -URI http://asc.fasb.org/extlink&amp;oid=84230637&amp;loc=d3e32621-109319<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 8<br> -URI http://asc.fasb.org/extlink&amp;oid=84230637&amp;loc=d3e32632-109319<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 8<br> -URI http://asc.fasb.org/extlink&amp;oid=84230637&amp;loc=d3e32632-109319<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 3<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=84230637&amp;loc=d3e32559-109319<br><br>Reference 3: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 6<br> -URI http://asc.fasb.org/extlink&amp;oid=84230637&amp;loc=d3e32621-109319<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 6<br> -URI http://asc.fasb.org/extlink&amp;oid=84230637&amp;loc=d3e32621-109319<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 8<br> -URI http://asc.fasb.org/extlink&amp;oid=84230637&amp;loc=d3e32632-109319<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)<br> -URI http://asc.fasb.org/extlink&amp;oid=84230637&amp;loc=d3e32537-109319<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DeferredTaxLiabilitiesAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DeferredTaxLiabilitiesFinancingArrangements">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of deferred tax liability attributable to taxable temporary differences from financing arrangements.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 6<br> -URI http://asc.fasb.org/extlink&amp;oid=84230637&amp;loc=d3e32621-109319<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 8<br> -URI http://asc.fasb.org/extlink&amp;oid=84230637&amp;loc=d3e32632-109319<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DeferredTaxLiabilitiesFinancingArrangements</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DeferredTaxLiabilitiesOther">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 8<br> -URI http://asc.fasb.org/extlink&amp;oid=84230637&amp;loc=d3e32632-109319<br><br>Reference 2: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 6<br> -URI http://asc.fasb.org/extlink&amp;oid=84230637&amp;loc=d3e32621-109319<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 6<br> -URI http://asc.fasb.org/extlink&amp;oid=84230637&amp;loc=d3e32621-109319<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 8<br> -URI http://asc.fasb.org/extlink&amp;oid=84230637&amp;loc=d3e32632-109319<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DeferredTaxLiabilitiesPropertyPlantAndEquipment</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ValuationAllowancesAndReservesPeriodIncreaseDecrease">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 235<br> -SubTopic 10<br> -Section S99<br> -Paragraph 4<br> -Subparagraph (SX 210.12-09)<br> -URI http://asc.fasb.org/extlink&amp;oid=120395691&amp;loc=d3e24092-122690<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ValuationAllowancesAndReservesPeriodIncreaseDecrease</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
</div>
</body>
</html>
</TEXT>
</DOCUMENT>
<DOCUMENT>
<TYPE>XML
<SEQUENCE>107
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<DESCRIPTION>IDEA: XBRL DOCUMENT
<TEXT>
<html>
<head>
<title></title>
<link rel="stylesheet" type="text/css" href="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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<body>
<span style="display: none;">v3.20.4</span><table class="report" border="0" cellspacing="2" id="idm140142731526936">
<tr>
<th class="tl" colspan="1" rowspan="1"><div style="width: 200px;"><strong>Income Taxes, Tax Credit Carryforwards (Details)<br> $ in Millions</strong></div></th>
<th class="th">
<div>Dec. 31, 2020 </div>
<div>USD ($)</div>
</th>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_IncomeTaxAuthorityNameAxis=us-gaap_InternalRevenueServiceIRSMember', window );">Federal [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_OperatingLossCarryforwardsLineItems', window );"><strong>Operating Loss Carryforwards [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_OperatingLossCarryforwards', window );">Net operating loss carryforwards</a></td>
<td class="nump">$ 243.3<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_IncomeTaxAuthorityNameAxis=us-gaap_InternalRevenueServiceIRSMember', window );">Federal [Member] | Research and Development [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="top.Show.showAR( this, 'defref_us-gaap_TaxCreditCarryforwardAmount', window );">Tax credit carryforwards</a></td>
<td class="nump">210.5<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_IncomeTaxAuthorityNameAxis=us-gaap_CaliforniaFranchiseTaxBoardMember', window );">California [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="top.Show.showAR( this, 'defref_us-gaap_OperatingLossCarryforwards', window );">Net operating loss carryforwards</a></td>
<td class="nump">346.3<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_IncomeTaxAuthorityNameAxis=us-gaap_CaliforniaFranchiseTaxBoardMember', window );">California [Member] | Research and Development [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="top.Show.showAR( this, 'defref_us-gaap_TaxCreditCarryforwardAmount', window );">Tax credit carryforwards</a></td>
<td class="nump">$ 87.4<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_OperatingLossCarryforwards">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 3<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=84230637&amp;loc=d3e32559-109319<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 3<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=84230637&amp;loc=d3e32559-109319<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_IncomeTaxAuthorityNameAxis=us-gaap_InternalRevenueServiceIRSMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_TaxCreditCarryforwardAxis=us-gaap_ResearchMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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_IncomeTaxAuthorityNameAxis=us-gaap_CaliforniaFranchiseTaxBoardMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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>
</div>
</body>
</html>
</TEXT>
</DOCUMENT>
<DOCUMENT>
<TYPE>XML
<SEQUENCE>108
<FILENAME>R72.htm
<DESCRIPTION>IDEA: XBRL DOCUMENT
<TEXT>
<html>
<head>
<title></title>
<link rel="stylesheet" type="text/css" href="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;">v3.20.4</span><table class="report" border="0" cellspacing="2" id="idm140142735872616">
<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, 2020</div></th>
<th class="th"><div>Dec. 31, 2019</div></th>
<th class="th"><div>Dec. 31, 2018</div></th>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="top.Show.showAR( this, 'defref_us-gaap_UnrecognizedTaxBenefits', window );">Beginning balance of unrecognized tax benefits</a></td>
<td class="nump">$ 69,784<span></span>
</td>
<td class="nump">$ 68,301<span></span>
</td>
<td class="nump">$ 78,014<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_UnrecognizedTaxBenefitsDecreasesResultingFromPriorPeriodTaxPositions', window );">Decrease for prior period tax positions</a></td>
<td class="num">(24,154)<span></span>
</td>
<td class="num">(867)<span></span>
</td>
<td class="num">(12,814)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_UnrecognizedTaxBenefitsIncreasesResultingFromPriorPeriodTaxPositions', window );">Increase for prior period tax positions</a></td>
<td class="nump">7,023<span></span>
</td>
<td class="nump">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="top.Show.showAR( this, 'defref_us-gaap_UnrecognizedTaxBenefitsIncreasesResultingFromCurrentPeriodTaxPositions', window );">Increase for current period tax positions</a></td>
<td class="nump">1,510<span></span>
</td>
<td class="nump">1,614<span></span>
</td>
<td class="nump">3,101<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_UnrecognizedTaxBenefits', window );">Ending balance of unrecognized tax benefits</a></td>
<td class="nump">54,163<span></span>
</td>
<td class="nump">69,784<span></span>
</td>
<td class="nump">68,301<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_UnrecognizedTaxBenefitsThatWouldImpactEffectiveTaxRate', window );">Unrecognized tax benefits that could impact effective tax rate, if recognized</a></td>
<td class="nump">6,400<span></span>
</td>
<td class="nump">400<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="top.Show.showAR( this, 'defref_us-gaap_UnrecognizedTaxBenefitsIncomeTaxPenaltiesAndInterestExpense', window );">Interest and penalties on unrecognized tax benefits</a></td>
<td class="nump">$ 300<span></span>
</td>
<td class="nump">$ 0<span></span>
</td>
<td class="nump">$ 0<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ReconciliationOfUnrecognizedTaxBenefitsExcludingAmountsPertainingToExaminedTaxReturnsRollForward">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ReconciliationOfUnrecognizedTaxBenefitsExcludingAmountsPertainingToExaminedTaxReturnsRollForward</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_UnrecognizedTaxBenefits">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of unrecognized tax benefits.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 45<br> -Paragraph 10B<br> -URI http://asc.fasb.org/extlink&amp;oid=120406818&amp;loc=SL37586934-109318<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 15A<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=84230637&amp;loc=SL6600010-109319<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 15A<br> -Subparagraph (a)(1)<br> -URI http://asc.fasb.org/extlink&amp;oid=84230637&amp;loc=SL6600010-109319<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 15<br> -Subparagraph (c)<br> -URI http://asc.fasb.org/extlink&amp;oid=84230637&amp;loc=d3e32718-109319<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 15A<br> -Subparagraph (a)(2)<br> -URI http://asc.fasb.org/extlink&amp;oid=84230637&amp;loc=SL6600010-109319<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 15A<br> -Subparagraph (a)(1)<br> -URI http://asc.fasb.org/extlink&amp;oid=84230637&amp;loc=SL6600010-109319<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_UnrecognizedTaxBenefitsIncreasesResultingFromPriorPeriodTaxPositions</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_UnrecognizedTaxBenefitsThatWouldImpactEffectiveTaxRate">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 15A<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=84230637&amp;loc=SL6600010-109319<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_UnrecognizedTaxBenefitsThatWouldImpactEffectiveTaxRate</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
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<span style="display: none;">v3.20.4</span><table class="report" border="0" cellspacing="2" id="idm140142719902568">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Collaborative Arrangements and Licensing Agreements, Biogen (Details)<br> $ in Thousands</strong></div></th>
<th class="th" colspan="2">1 Months Ended</th>
<th class="th" colspan="9">3 Months Ended</th>
<th class="th" colspan="3">12 Months Ended</th>
<th class="th" colspan="1"></th>
</tr>
<tr>
<th class="th">
<div>Sep. 30, 2013 </div>
<div>USD ($) </div>
<div>PerformanceObligation</div>
</th>
<th class="th">
<div>Dec. 31, 2012 </div>
<div>USD ($) </div>
<div>Program</div>
</th>
<th class="th">
<div>Sep. 30, 2020 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Mar. 31, 2020 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Dec. 31, 2019 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Sep. 30, 2019 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Jun. 30, 2019 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Dec. 31, 2018 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Sep. 30, 2018 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Jun. 30, 2018 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Dec. 31, 2017 </div>
<div>USD ($) </div>
<div>PerformanceObligation</div>
</th>
<th class="th">
<div>Dec. 31, 2020 </div>
<div>USD ($) </div>
<div>Medicine </div>
<div>Program </div>
<div>Country</div>
</th>
<th class="th">
<div>Dec. 31, 2019 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Dec. 31, 2018 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Apr. 30, 2018 </div>
<div>USD ($) </div>
<div>PerformanceObligation</div>
</th>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ProceedsFromIssuanceOfCommonStock', window );">Proceeds from issuance of common stock</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 0<span></span>
</td>
<td class="nump">$ 0<span></span>
</td>
<td class="nump">$ 447,965<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">729,264<span></span>
</td>
<td class="nump">1,122,599<span></span>
</td>
<td class="nump">599,674<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_srt_ProductOrServiceAxis=ions_SpinrazaRoyaltiesMember', window );">SPINRAZA Royalties [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">286,583<span></span>
</td>
<td class="nump">292,992<span></span>
</td>
<td class="nump">237,930<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_srt_ProductOrServiceAxis=ions_LicensingAndOtherRoyaltiesMember', window );">Licensing and Other Royalties [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">8,117<span></span>
</td>
<td class="nump">17,205<span></span>
</td>
<td class="nump">14,755<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_srt_ProductOrServiceAxis=ions_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember', window );">R&amp;D Revenue [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 364,565<span></span>
</td>
<td class="nump">770,149<span></span>
</td>
<td class="nump">344,752<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementsAndLicensingAgreementsBiogenMember', window );">Biogen [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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="top.Show.showAR( this, 'defref_ions_NumberOfMedicinesBeingDeveloped', window );">Number of medicines currently being developed | Medicine</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</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">8<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 408,600<span></span>
</td>
<td class="nump">473,600<span></span>
</td>
<td class="nump">$ 375,000<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="top.Show.showAR( this, 'defref_us-gaap_ContractWithCustomerLiability', window );">Deferred revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 525,800<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 465,800<span></span>
</td>
<td class="nump">$ 525,800<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="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementsAndLicensingAgreementsBiogenMember', window );">Biogen [Member] | Revenue [Member] | Strategic Partner [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ConcentrationRiskPercentage1', window );">Concentration percentage</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">56.00%<span></span>
</td>
<td class="nump">42.00%<span></span>
</td>
<td class="nump">63.00%<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="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementsAndLicensingAgreementsBiogenMember', window );">Biogen [Member] | Minimum [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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="top.Show.showAR( this, 'defref_ions_CumulativePaymentsReceived', window );">Cumulative payments received</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</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>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementsAndLicensingAgreementsBiogenMember', window );">Biogen [Member] | SPINRAZA Royalties [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">286,600<span></span>
</td>
<td class="nump">$ 293,000<span></span>
</td>
<td class="nump">$ 237,900<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementsAndLicensingAgreementsBiogenMember', window );">Biogen [Member] | R&amp;D Revenue [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 122,000<span></span>
</td>
<td class="nump">180,600<span></span>
</td>
<td class="nump">$ 137,100<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2012WithBiogenMember', window );">SPINRAZA [Member] | Minimum [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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="top.Show.showAR( this, 'defref_ions_NumberOfCountriesWhereDrugIsApprovedForUse', window );">Number of countries where SPINRAZA is approved for use | Country</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">50<span></span>
</td>
<td class="text">&#160;<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="top.Show.showAR( this, 'defref_ions_CumulativeRevenueFromContractWithCustomerExcludingAssessedTax', window );">Cumulative revenue earned</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</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">$ 1,300,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_RoyaltyPercentageReceivedOnNetSalesOfDrug', window );">Royalty percentage received on net sales of drug</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">11.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2012WithBiogenMember', window );">SPINRAZA [Member] | Maximum [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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="top.Show.showAR( this, 'defref_ions_RoyaltyPercentageReceivedOnNetSalesOfDrug', window );">Royalty percentage received on net sales of drug</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">15.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2012WithBiogenMember', window );">SPINRAZA [Member] | SPINRAZA Royalties [Member] | Minimum [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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="top.Show.showAR( this, 'defref_ions_CumulativeRevenueFromContractWithCustomerExcludingAssessedTax', window );">Cumulative revenue earned</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</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">$ 930,000<span></span>
</td>
<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="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2012WithBiogenMember', window );">SPINRAZA [Member] | R&amp;D Revenue [Member] | Minimum [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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="top.Show.showAR( this, 'defref_ions_CumulativeRevenueFromContractWithCustomerExcludingAssessedTax', window );">Cumulative revenue earned</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</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">$ 435,000<span></span>
</td>
<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="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2017WithBiogenMember', window );">New Antisense Medicines for the Treatment of SMA [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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="top.Show.showAR( this, 'defref_ions_RoyaltyPercentageReceivedOnNetSalesOfDrug', window );">Royalty percentage received on net sales of drug</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">20.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="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>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_MaximumAmountOfPaymentsReceivableForLicenseFeesAndMilestones', window );">Maximum amount of payments receivable for license fees and milestones</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 1,200,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_MaximumAmountOfPaymentsReceivableForDevelopmentMilestones', window );">Maximum amount of payments receivable for development milestones</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">80,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_MaximumAmountOfPaymentsReceivableForCommercializationMilestones', window );">Maximum amount of payments receivable for commercialization milestones</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">180,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_MaximumAmountOfPaymentsReceivableForSalesMilestones', window );">Maximum amount of payments receivable for sales milestones</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">800,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_NextPotentialPayment', window );">Next prospective payment</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</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>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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>
<td class="text">&#160;<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="top.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">$ 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>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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">8,300<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember', window );">2018 Strategic Neurology [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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="top.Show.showAR( this, 'defref_ions_CumulativePaymentsReceived', window );">Cumulative payments received</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</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">$ 1,050,000<span></span>
</td>
<td class="text">&#160;<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="top.Show.showAR( this, 'defref_ions_RoyaltyPercentageReceivedOnNetSalesOfDrug', window );">Royalty percentage received on net sales of drug</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">20.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="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>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_NextPotentialPayment', window );">Next prospective payment</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 7,500<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations', window );">Number of separate performance obligations | PerformanceObligation</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">1<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_RevenueFromContractWithCustomerTransactionPrice', window );">Transaction price</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 552,000<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_TermOfCollaborationAgreement', window );">Term of collaboration agreement</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">10 years<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_UpfrontPaymentReceivedIncludingPurchaseOfStock', window );">Upfront payment received, including purchase of stock</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">1,000,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ProceedsFromIssuanceOfCommonStock', window );">Proceeds from issuance of common stock</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 625,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_PercentageCashPremiumPaidOnSharesPurchased', window );">Percentage cash premium paid on shares purchased</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">25.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_MaximumAmountOfPaymentsReceivablePerDrugForSubstantiveMilestonePayments', window );">Maximum amount of payments receivable per drug for substantive milestone payments</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 270,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_NumberOfProgramsBeingAdvanced', window );">Number of programs being advanced | 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="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">8<span></span>
</td>
<td class="text">&#160;<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="top.Show.showAR( this, 'defref_ions_PremiumPaidOnSharesPurchased', window );">Premium paid on shares purchased</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 177,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_CumulativePaymentsIncludedInTransactionPriceForPerformanceObligation', window );">Cumulative payments included in transaction price for performance obligation</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 608,000<span></span>
</td>
<td class="text">&#160;<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="top.Show.showAR( this, 'defref_ions_MilestonePaymentsAchievedAndIncludedInTransactionPriceForPerformanceObligation', window );">Milestone payments achieved and included in transaction price for performance obligation</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">11,000<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>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember', window );">2013 Strategic Neurology [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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="top.Show.showAR( this, 'defref_ions_UpfrontPaymentReceived', window );">Upfront payment received</a></td>
<td class="nump">$ 100,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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="top.Show.showAR( this, 'defref_ions_NextPotentialPayment', window );">Next prospective payment</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</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>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations', window );">Number of separate performance obligations | PerformanceObligation</a></td>
<td class="nump">1<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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="top.Show.showAR( this, 'defref_ions_RevenueFromContractWithCustomerTransactionPrice', window );">Transaction price</a></td>
<td class="nump">$ 100,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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="top.Show.showAR( this, 'defref_ions_NumberOfMedicinesCurrentlyBeingAdvanced', window );">Number of medicines currently being advanced | Medicine</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">6<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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">$ 18,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="num">$ (16,500)<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>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember', window );">2013 Strategic 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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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="top.Show.showAR( this, 'defref_ions_CumulativePaymentsReceived', window );">Cumulative payments received</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 270,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember', window );">2013 Strategic Neurology [Member] | Licensing and Other Royalties [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="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>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember', window );">2013 Strategic Neurology [Member] | R&amp;D Revenue [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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="top.Show.showAR( this, 'defref_ions_CumulativePaymentsIncludedInTransactionPriceForPerformanceObligation', window );">Cumulative payments included in transaction price for performance obligation</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 145,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
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<td class="text">&#160;<span></span>
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</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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#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="top.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>
<td class="text">&#160;<span></span>
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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>
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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>
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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>
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</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="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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>
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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>
</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>
<td class="text">&#160;<span></span>
</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>
</tr>
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<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember', window );">2013 Strategic Neurology [Member] | Medicines for Multiple System Atrophy [Member]</a></td>
<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<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>
<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="top.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>
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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>
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<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_NumberOfMedicinesCurrentlyBeingAdvanced', window );">Number of medicines currently being advanced | Medicine</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">1<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember', window );">2013 Strategic Neurology [Member] | Medicines for Undisclosed Targets [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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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>
<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>
<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>
<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>
</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>
<td class="text">&#160;<span></span>
</td>
<td class="nump">1<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
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<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember', window );">2013 Strategic Neurology [Member] | Antisense Molecule [Member]</a></td>
<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
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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="top.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>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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="top.Show.showAR( this, 'defref_ions_MaximumAmountOfPaymentsReceivablePerDrugOrProgramForLicenseFeesAndSubstantiveMilestonePayments', window );">Maximum amount of payments receivable per program for license fee and milestone payments</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 260,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
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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="top.Show.showAR( this, 'defref_ions_MaximumAmountOfPaymentsReceivablePerDrugOrProgramForDevelopmentMilestones', window );">Maximum amount of payments receivable per program for development milestones</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</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>
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<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_MaximumAmountOfPaymentsReceivablePerDrugOrProgramForRegulatoryMilestones', window );">Maximum amount of payments receivable per program for regulatory milestones</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">130,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
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<td class="text">&#160;<span></span>
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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="top.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>
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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>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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">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="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>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember', window );">2013 Strategic Neurology [Member] | Tofersen [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>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="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>
<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="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember', window );">2013 Strategic Neurology [Member] | ION859 [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>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">8,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember', window );">2013 Strategic Neurology [Member] | ION464 [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>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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">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>
<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="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember', window );">2013 Strategic Neurology [Member] | ION541 [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>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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">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>
<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="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember', 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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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="top.Show.showAR( this, 'defref_ions_CumulativePaymentsReceived', window );">Cumulative payments received</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</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">154,000<span></span>
</td>
<td class="text">&#160;<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="top.Show.showAR( this, 'defref_ions_UpfrontPaymentReceived', window );">Upfront payment received</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 30,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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="top.Show.showAR( this, 'defref_ions_NextPotentialPayment', window );">Next prospective payment</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</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>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_MaximumAmountOfPaymentsReceivablePerDrugOrProgramForLicenseFeesAndSubstantiveMilestonePayments', window );">Maximum amount of payments receivable per program for license fee and milestone payments</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">210,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_MaximumAmountOfPaymentsReceivablePerDrugOrProgramForDevelopmentMilestones', window );">Maximum amount of payments receivable per program for development milestones</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</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>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_MaximumAmountOfPaymentsReceivablePerDrugOrProgramForRegulatoryMilestones', window );">Maximum amount of payments receivable per program for regulatory milestones</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">130,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_NumberOfProgramsUnderWhichDrugsAreToBeDevelopedAndCommercialized', window );">Number of programs under which drugs are to be developed and commercialized | Program</a></td>
<td class="text">&#160;<span></span>
</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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 6,300<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember', window );">2012 Neurology [Member] | R&amp;D Revenue [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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="top.Show.showAR( this, 'defref_ions_CumulativePaymentsIncludedInTransactionPriceForPerformanceObligation', window );">Cumulative payments included in transaction price for performance obligation</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">40,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember', window );">2012 Neurology [Member] | IONIS-MAPT [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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="top.Show.showAR( this, 'defref_ions_CumulativePaymentsIncludedInTransactionPriceForPerformanceObligation', window );">Cumulative payments included in transaction price for performance obligation</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="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>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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">$ 12,000<span></span>
</td>
<td class="nump">$ 7,500<span></span>
</td>
<td class="nump">12,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 7,500<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 19,500<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_TermOfExtensionStudy', window );">Term of extension study</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">1 year<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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">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>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember', window );">2012 Neurology [Member] | ION582 [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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">$ 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>
<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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</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_MaximumAmountOfPaymentsReceivableForCommercializationMilestones">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The maximum amount of payments receivable for commercialization milestones under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MaximumAmountOfPaymentsReceivableForCommercializationMilestones</td>
</tr>
<tr>
<td style="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_MaximumAmountOfPaymentsReceivableForDevelopmentMilestones">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The maximum amount of payments receivable for development milestones under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MaximumAmountOfPaymentsReceivableForDevelopmentMilestones</td>
</tr>
<tr>
<td style="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_MaximumAmountOfPaymentsReceivableForLicenseFeesAndMilestones">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Maximum amount of payments receivable for license fees and milestone payments under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MaximumAmountOfPaymentsReceivableForLicenseFeesAndMilestones</td>
</tr>
<tr>
<td style="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_MaximumAmountOfPaymentsReceivableForSalesMilestones">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The maximum amount of payments receivable for sales milestones under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MaximumAmountOfPaymentsReceivableForSalesMilestones</td>
</tr>
<tr>
<td style="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_MaximumAmountOfPaymentsReceivablePerDrugForSubstantiveMilestonePayments">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The maximum amount of payments receivable per drug for substantive milestone payments under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MaximumAmountOfPaymentsReceivablePerDrugForSubstantiveMilestonePayments</td>
</tr>
<tr>
<td style="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_MaximumAmountOfPaymentsReceivablePerDrugOrProgramForDevelopmentMilestones">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The maximum amount of payments receivable per drug or program for development milestone payments under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MaximumAmountOfPaymentsReceivablePerDrugOrProgramForDevelopmentMilestones</td>
</tr>
<tr>
<td style="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_MaximumAmountOfPaymentsReceivablePerDrugOrProgramForLicenseFeesAndSubstantiveMilestonePayments">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The maximum amount of payments receivable per drug or program for license fees and/or substantive milestone payments under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MaximumAmountOfPaymentsReceivablePerDrugOrProgramForLicenseFeesAndSubstantiveMilestonePayments</td>
</tr>
<tr>
<td style="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_MaximumAmountOfPaymentsReceivablePerDrugOrProgramForRegulatoryMilestones">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The maximum amount of payments receivable per drug or program for regulatory milestone payments under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MaximumAmountOfPaymentsReceivablePerDrugOrProgramForRegulatoryMilestones</td>
</tr>
<tr>
<td style="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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</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_NextPotentialPayment">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The next potential payment to be earned under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_NextPotentialPayment</td>
</tr>
<tr>
<td style="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_NumberOfCountriesWhereDrugIsApprovedForUse">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The number of countries where the drug is approved for treatment in patients.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_NumberOfCountriesWhereDrugIsApprovedForUse</td>
</tr>
<tr>
<td style="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_NumberOfMedicinesBeingDeveloped">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The number of medicines currently being developed under the collaboration agreement(s).</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_NumberOfMedicinesBeingDeveloped</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:integerItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_NumberOfMedicinesCurrentlyBeingAdvanced">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</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_NumberOfProgramsBeingAdvanced">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The number of programs being advanced under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_NumberOfProgramsBeingAdvanced</td>
</tr>
<tr>
<td style="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_NumberOfProgramsUnderWhichDrugsAreToBeDevelopedAndCommercialized">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The number of programs under which drugs are to be developed and commercialized under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_NumberOfProgramsUnderWhichDrugsAreToBeDevelopedAndCommercialized</td>
</tr>
<tr>
<td style="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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</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>num: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_PremiumPaidOnSharesPurchased">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</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_RoyaltyPercentageReceivedOnNetSalesOfDrug">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Royalty percentage received on the net sales of a drug by a collaboration partner under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_RoyaltyPercentageReceivedOnNetSalesOfDrug</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>num: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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</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_TermOfExtensionStudy">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Term of long-term open label extension study, in which patients participating in double blind placebo controlled trials of new medications are invited, on completion of the initial trial, to take the study drug for some further period, for example, 'P1Y5M13D' represents reported fact of one year, five months, and thirteen days.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_TermOfExtensionStudy</td>
</tr>
<tr>
<td style="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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 42<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e9054-108599<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 275<br> -SubTopic 10<br> -Section 50<br> -Paragraph 18<br> -URI http://asc.fasb.org/extlink&amp;oid=99393423&amp;loc=d3e6351-108592<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 825<br> -SubTopic 10<br> -Section 50<br> -Paragraph 20<br> -URI http://asc.fasb.org/extlink&amp;oid=121572278&amp;loc=d3e13531-108611<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 825<br> -SubTopic 10<br> -Section 50<br> -Paragraph 21<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=121572278&amp;loc=d3e13537-108611<br><br>Reference 5: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 275<br> -SubTopic 10<br> -Section 50<br> -Paragraph 20<br> -URI http://asc.fasb.org/extlink&amp;oid=99393423&amp;loc=d3e6404-108592<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>num: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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 45<br> -Paragraph 1<br> -URI http://asc.fasb.org/extlink&amp;oid=121556615&amp;loc=SL49130531-203044<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 50<br> -Paragraph 8<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=121604090&amp;loc=SL49130549-203045<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 45<br> -Paragraph 2<br> -URI http://asc.fasb.org/extlink&amp;oid=121556615&amp;loc=SL49130532-203044<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 14<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=121586364&amp;loc=d3e3255-108585<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 30<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e8906-108599<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 40<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e9031-108599<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 41<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e9038-108599<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e8933-108599<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e8933-108599<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=121604090&amp;loc=SL49130543-203045<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 22<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e8736-108599<br><br>Reference 8: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 22<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e8736-108599<br><br>Reference 9: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 42<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e9054-108599<br><br>Reference 10: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 50<br> -Paragraph 5<br> -URI http://asc.fasb.org/extlink&amp;oid=121604090&amp;loc=SL49130545-203045<br><br>Reference 11: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 924<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 11.L)<br> -URI http://asc.fasb.org/extlink&amp;oid=6472922&amp;loc=d3e499488-122856<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>
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<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">srt_ProductOrServiceAxis=ions_SpinrazaRoyaltiesMember</td>
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<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">srt_ProductOrServiceAxis=ions_LicensingAndOtherRoyaltiesMember</td>
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<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">srt_ProductOrServiceAxis=ions_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember</td>
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<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementsAndLicensingAgreementsBiogenMember</td>
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<tr>
<td><strong> Name:</strong></td>
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<tr>
<td><strong> Name:</strong></td>
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<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2012WithBiogenMember</td>
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<tr>
<td><strong> Name:</strong></td>
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<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2017WithBiogenMember</td>
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<a href="javascript:void(0);" onclick="top.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_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember</td>
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<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember</td>
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<td style="white-space:nowrap;">srt_ProductOrServiceAxis=ions_MedicinesForParkinsonsDiseaseMember</td>
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<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">srt_ProductOrServiceAxis=ions_MedicinesForAmyotrophicLateralSclerosisMember</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<td style="white-space:nowrap;">srt_ProductOrServiceAxis=ions_MedicinesForUndisclosedTargetsMember</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="top.Show.hideAR();">X</a></td></tr>
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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;">v3.20.4</span><table class="report" border="0" cellspacing="2" id="idm140142731586552">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Collaborative Arrangements and Licensing Agreements, AstraZeneca (Details)<br> $ in Thousands</strong></div></th>
<th class="th" colspan="2">1 Months Ended</th>
<th class="th" colspan="7">3 Months Ended</th>
<th class="th" colspan="3">12 Months Ended</th>
</tr>
<tr>
<th class="th">
<div>Jul. 31, 2015 </div>
<div>USD ($) </div>
<div>PerformanceObligation</div>
</th>
<th class="th">
<div>Dec. 31, 2012 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Dec. 31, 2020 </div>
<div>USD ($) </div>
<div>Agreement </div>
<div>Medicine</div>
</th>
<th class="th">
<div>Jun. 30, 2020 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Mar. 31, 2020 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Dec. 31, 2019 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Dec. 31, 2018 </div>
<div>USD ($) </div>
<div>Program</div>
</th>
<th class="th">
<div>Sep. 30, 2018 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Mar. 31, 2018 </div>
<div>USD ($) </div>
<div>LicenseFee</div>
</th>
<th class="th">
<div>Dec. 31, 2020 </div>
<div>USD ($) </div>
<div>Agreement </div>
<div>Medicine</div>
</th>
<th class="th">
<div>Dec. 31, 2019 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Dec. 31, 2018 </div>
<div>USD ($)</div>
</th>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 729,264<span></span>
</td>
<td class="nump">$ 1,122,599<span></span>
</td>
<td class="nump">$ 599,674<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_srt_ProductOrServiceAxis=ions_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember', 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="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 364,565<span></span>
</td>
<td class="nump">770,149<span></span>
</td>
<td class="nump">$ 344,752<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementsAndLicensingAgreementsAstrazenecaMember', window );">AstraZeneca [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="top.Show.showAR( this, 'defref_ions_NumberOfCollaborationAgreements', window );">Number of collaboration agreements | 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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">2<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ContractWithCustomerLiability', window );">Deferred revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 10,000<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="nump">$ 10,000<span></span>
</td>
<td class="nump">$ 25,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementsAndLicensingAgreementsAstrazenecaMember', window );">AstraZeneca [Member] | Revenue [Member] | Strategic Partner [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="top.Show.showAR( this, 'defref_us-gaap_ConcentrationRiskPercentage1', window );">Concentration percentage</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">12.00%<span></span>
</td>
<td class="nump">3.00%<span></span>
</td>
<td class="nump">20.00%<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementsAndLicensingAgreementsAstrazenecaMember', window );">AstraZeneca [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="top.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="top.Show.showAR( this, 'defref_ions_CumulativePaymentsReceived', window );">Cumulative payments received</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 380,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</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">$ 380,000<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="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementsAndLicensingAgreementsAstrazenecaMember', window );">AstraZeneca [Member] | R&amp;D Revenue [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 88,000<span></span>
</td>
<td class="nump">$ 28,100<span></span>
</td>
<td class="nump">$ 120,700<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJuly2015WithAstrazenecaMember', 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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="top.Show.showAR( this, 'defref_ions_NumberOfCollaborationAgreements', window );">Number of collaboration agreements | Agreement</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">1<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="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="top.Show.showAR( this, 'defref_ions_NumberOfLicensedMedicines', window );">Number of licensed medicines | Medicine</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>
<td class="text">&#160;<span></span>
</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>
<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="top.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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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="top.Show.showAR( this, 'defref_ions_MinimumAmountOfPaymentsReceivableForLicenseFeesAndSubstantiveMilestones', window );">Minimum amount of payments receivable for license fees and milestones</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 5,500,000<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">$ 5,500,000<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="top.Show.showAR( this, 'defref_ions_MaximumAmountOfPaymentsReceivableForDevelopmentMilestones', window );">Maximum amount of payments receivable for development milestones</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">1,100,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">1,100,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_MaximumAmountOfPaymentsReceivableForRegulatoryMilestones', window );">Maximum amount of payments receivable for regulatory milestones</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">2,900,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">2,900,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_MaximumAmountOfPaymentsReceivableForCommercializationMilestones', window );">Maximum amount of payments receivable for commercialization milestones</a></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>
<td class="text">&#160;<span></span>
</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="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_NextPotentialPayment', window );">Next prospective payment</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">30,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations', window );">Number of separate performance obligations | PerformanceObligation</a></td>
<td class="nump">1<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_RevenueFromContractWithCustomerTransactionPrice', window );">Transaction price</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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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="top.Show.showAR( this, 'defref_ions_NumberOfLicenseFeesEarned', window );">Number of license fees earned | LicenseFee</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</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="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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">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>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJuly2015WithAstrazenecaMember', 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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="top.Show.showAR( this, 'defref_ions_CumulativePaymentsReceived', window );">Cumulative payments received</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">235,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</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">235,000<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="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJuly2015WithAstrazenecaMember', window );">Cardiovascular, Renal and Metabolic Diseases [Member] | ION455 [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="top.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="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">30,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJuly2015WithAstrazenecaMember', window );">Cardiovascular, Renal and Metabolic Diseases [Member] | ION532 and ION449 [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="top.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="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="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>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJuly2015WithAstrazenecaMember', window );">Cardiovascular, Renal and Metabolic Diseases [Member] | ION532 [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="top.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="top.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">$ 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="nump">$ 30,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJuly2015WithAstrazenecaMember', window );">Cardiovascular, Renal and Metabolic Diseases [Member] | ION839 [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="top.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="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 10,000<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="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJuly2015WithAstrazenecaMember', window );">Cardiovascular, Renal and Metabolic Diseases [Member] | ION449[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="top.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="top.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">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="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="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJuly2015WithAstrazenecaMember', window );">Cardiovascular, Renal and Metabolic Diseases [Member] | R&amp;D Revenue [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="top.Show.showAR( this, 'defref_ions_CumulativePaymentsIncludedInTransactionPriceForPerformanceObligation', window );">Cumulative payments included in transaction price for performance obligation</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 90,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 90,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithAstrazenecaMember', window );">Oncology [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="top.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="top.Show.showAR( this, 'defref_ions_NumberOfCollaborationAgreements', window );">Number of collaboration agreements | Agreement</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">1<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="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 custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_UpfrontPaymentReceived', window );">Upfront payment received</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 31,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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="top.Show.showAR( this, 'defref_ions_MinimumAmountOfPaymentsReceivableForLicenseFeesAndSubstantiveMilestones', window );">Minimum amount of payments receivable for license fees and milestones</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 265,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</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">$ 265,000<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="top.Show.showAR( this, 'defref_ions_MaximumAmountOfPaymentsReceivableForDevelopmentMilestones', window );">Maximum amount of payments receivable for development milestones</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">107,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</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">107,000<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="top.Show.showAR( this, 'defref_ions_MaximumAmountOfPaymentsReceivableForRegulatoryMilestones', window );">Maximum amount of payments receivable for regulatory milestones</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">105,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="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>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_NextPotentialPayment', window );">Next prospective payment</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">12,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">12,000<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="top.Show.showAR( this, 'defref_ions_NumberOfProgramsAdvanced', window );">Number of programs advanced | 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="nump">2<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithAstrazenecaMember', window );">Oncology [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="top.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="top.Show.showAR( this, 'defref_ions_CumulativePaymentsReceived', window );">Cumulative payments received</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 140,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</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">140,000<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="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithAstrazenecaMember', window );">Oncology [Member] | Danvatirsen [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="top.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="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 17,500<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithAstrazenecaMember', window );">Oncology [Member] | ION736 [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="top.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="top.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">$ 13,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 10,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 13,000<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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</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_MaximumAmountOfPaymentsReceivableForCommercializationMilestones">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The maximum amount of payments receivable for commercialization milestones under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MaximumAmountOfPaymentsReceivableForCommercializationMilestones</td>
</tr>
<tr>
<td style="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_MaximumAmountOfPaymentsReceivableForDevelopmentMilestones">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The maximum amount of payments receivable for development milestones under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MaximumAmountOfPaymentsReceivableForDevelopmentMilestones</td>
</tr>
<tr>
<td style="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_MaximumAmountOfPaymentsReceivableForRegulatoryMilestones">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The maximum amount of payments receivable for regulatory milestones under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MaximumAmountOfPaymentsReceivableForRegulatoryMilestones</td>
</tr>
<tr>
<td style="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_MinimumAmountOfPaymentsReceivableForLicenseFeesAndSubstantiveMilestones">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The minimum amount of payments receivable for license fees and substantive milestones under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MinimumAmountOfPaymentsReceivableForLicenseFeesAndSubstantiveMilestones</td>
</tr>
<tr>
<td style="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_NextPotentialPayment">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The next potential payment to be earned under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_NextPotentialPayment</td>
</tr>
<tr>
<td style="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_NumberOfCollaborationAgreements">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The number of collaboration agreements with the collaboration partner.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_NumberOfCollaborationAgreements</td>
</tr>
<tr>
<td style="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_NumberOfLicenseFeesEarned">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The number of license fees earned during the period under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_NumberOfLicenseFeesEarned</td>
</tr>
<tr>
<td style="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_NumberOfLicensedMedicines">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The number of medicines that have been licensed under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_NumberOfLicensedMedicines</td>
</tr>
<tr>
<td style="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_NumberOfProgramsAdvanced">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The number of programs advanced under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_NumberOfProgramsAdvanced</td>
</tr>
<tr>
<td style="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_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</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_UpfrontPaymentReceived">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 42<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e9054-108599<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 275<br> -SubTopic 10<br> -Section 50<br> -Paragraph 18<br> -URI http://asc.fasb.org/extlink&amp;oid=99393423&amp;loc=d3e6351-108592<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 825<br> -SubTopic 10<br> -Section 50<br> -Paragraph 20<br> -URI http://asc.fasb.org/extlink&amp;oid=121572278&amp;loc=d3e13531-108611<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 825<br> -SubTopic 10<br> -Section 50<br> -Paragraph 21<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=121572278&amp;loc=d3e13537-108611<br><br>Reference 5: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 275<br> -SubTopic 10<br> -Section 50<br> -Paragraph 20<br> -URI http://asc.fasb.org/extlink&amp;oid=99393423&amp;loc=d3e6404-108592<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>num: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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 45<br> -Paragraph 1<br> -URI http://asc.fasb.org/extlink&amp;oid=121556615&amp;loc=SL49130531-203044<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 50<br> -Paragraph 8<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=121604090&amp;loc=SL49130549-203045<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 45<br> -Paragraph 2<br> -URI http://asc.fasb.org/extlink&amp;oid=121556615&amp;loc=SL49130532-203044<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 30<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e8906-108599<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 40<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e9031-108599<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 41<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e9038-108599<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e8933-108599<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e8933-108599<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=121604090&amp;loc=SL49130543-203045<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 22<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e8736-108599<br><br>Reference 8: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 22<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e8736-108599<br><br>Reference 9: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 42<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e9054-108599<br><br>Reference 10: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 50<br> -Paragraph 5<br> -URI http://asc.fasb.org/extlink&amp;oid=121604090&amp;loc=SL49130545-203045<br><br>Reference 11: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 924<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 11.L)<br> -URI http://asc.fasb.org/extlink&amp;oid=6472922&amp;loc=d3e499488-122856<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember</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_CollaborativeArrangementsAndLicensingAgreementsAstrazenecaMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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_CollaborativeArrangementsAndLicensingAgreementsAstrazenecaMember</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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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_srt_RangeAxis=srt_MinimumMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJuly2015WithAstrazenecaMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJuly2015WithAstrazenecaMember</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_Ion455Member">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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_Ion455Member</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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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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_Ion532AndIon449Member</td>
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<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<tr>
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<td></td>
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<tr>
<td><strong> Period Type:</strong></td>
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<a href="javascript:void(0);" onclick="top.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="top.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="top.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="top.Show.hideAR();">X</a></td></tr>
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<a href="javascript:void(0);" onclick="top.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_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithAstrazenecaMember</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="top.Show.hideAR();">X</a></td></tr>
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<a href="javascript:void(0);" onclick="top.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_DanvatirsenMember</td>
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<td>na</td>
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<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
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</DOCUMENT>
<DOCUMENT>
<TYPE>XML
<SEQUENCE>111
<FILENAME>R75.htm
<DESCRIPTION>IDEA: XBRL DOCUMENT
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<html>
<head>
<title></title>
<link rel="stylesheet" type="text/css" href="report.css">
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<span style="display: none;">v3.20.4</span><table class="report" border="0" cellspacing="2" id="idm140142814245880">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Collaborative Arrangements and Licensing Agreements, Bayer (Details)<br> $ in Thousands</strong></div></th>
<th class="th" colspan="2">1 Months Ended</th>
<th class="th" colspan="2">3 Months Ended</th>
<th class="th" colspan="3">12 Months Ended</th>
</tr>
<tr>
<th class="th">
<div>Feb. 28, 2017 </div>
<div>USD ($) </div>
<div>PerformanceObligation</div>
</th>
<th class="th">
<div>May 31, 2015 </div>
<div>USD ($) </div>
<div>PerformanceObligation</div>
</th>
<th class="th">
<div>Dec. 31, 2019 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Jun. 30, 2015 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Dec. 31, 2020 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Dec. 31, 2019 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Dec. 31, 2018 </div>
<div>USD ($)</div>
</th>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 729,264<span></span>
</td>
<td class="nump">$ 1,122,599<span></span>
</td>
<td class="nump">$ 599,674<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_srt_ProductOrServiceAxis=ions_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember', window );">R&amp;D Revenue [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="top.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">364,565<span></span>
</td>
<td class="nump">770,149<span></span>
</td>
<td class="nump">$ 344,752<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementsAndLicensingAgreementsBayerMember', window );">Bayer [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="top.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="top.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">$ 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="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ContractWithCustomerLiability', window );">Deferred revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 2,400<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 0<span></span>
</td>
<td class="nump">$ 2,400<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementsAndLicensingAgreementsBayerMember', window );">Bayer [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="top.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="top.Show.showAR( this, 'defref_us-gaap_ConcentrationRiskPercentage1', window );">Concentration percentage</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">0.00%<span></span>
</td>
<td class="nump">1.00%<span></span>
</td>
<td class="nump">1.00%<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementsAndLicensingAgreementsBayerMember', window );">Bayer [Member] | R&amp;D Revenue [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="top.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">$ 3,200<span></span>
</td>
<td class="nump">$ 14,300<span></span>
</td>
<td class="nump">$ 5,000<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMay2015WithBayerMember', window );">Bayer [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="top.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="top.Show.showAR( this, 'defref_ions_UpfrontPaymentReceived', window );">Upfront payment received</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 100,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="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>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_MaximumAmountOfPaymentsReceivableForLicenseFeesAndMilestones', window );">Maximum amount of payments receivable for license fees and milestones</a></td>
<td class="text">&#160;<span></span>
</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">385,000<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="top.Show.showAR( this, 'defref_ions_MaximumAmountOfPaymentsReceivableForDevelopmentMilestones', window );">Maximum amount of payments receivable for development milestones</a></td>
<td class="text">&#160;<span></span>
</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">125,000<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="top.Show.showAR( this, 'defref_ions_MaximumAmountOfPaymentsReceivableForCommercializationMilestones', window );">Maximum amount of payments receivable for commercialization milestones</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 110,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_RoyaltyPercentageReceivedOnGrossMarginsOfDrugsUnderCollaborationAgreement', window );">Royalty percentage received on gross margins of both drugs combined</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">20.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_NextPotentialPayment', window );">Next prospective payment</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 20,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations', window );">Number of separate performance obligations | PerformanceObligation</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">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>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMay2015WithBayerMember', window );">Bayer [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="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="top.Show.showAR( this, 'defref_ions_CumulativePaymentsReceived', window );">Cumulative payments received</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMay2015WithBayerMember', window );">Bayer [Member] | R&amp;D Services for IONIS-FXI-L [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="top.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="top.Show.showAR( this, 'defref_ions_RevenueFromContractWithCustomerTransactionPrice', window );">Transaction price</a></td>
<td class="nump">$ 10,100<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>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementAmendedInFebruary2017WithBayerMember', window );">Bayer [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="top.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="top.Show.showAR( this, 'defref_ions_UpfrontPaymentReceived', window );">Upfront payment received</a></td>
<td class="nump">75,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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="top.Show.showAR( this, 'defref_ions_PaymentReceivedForAdvancingPrograms', window );">Payment received for advancing programs</a></td>
<td class="nump">$ 75,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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="top.Show.showAR( this, 'defref_ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations', window );">Number of separate performance obligations | PerformanceObligation</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>
<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="top.Show.showAR( this, 'defref_ions_RevenueFromContractWithCustomerNumberOfNewPerformanceObligations', window );">Number of new performance obligations | PerformanceObligation</a></td>
<td class="nump">2<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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="top.Show.showAR( this, 'defref_ions_RevenueFromContractWithCustomerTransactionPrice', window );">Transaction price</a></td>
<td class="nump">$ 75,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementAmendedInFebruary2017WithBayerMember', window );">Bayer [Member] | IONIS-FXI-L [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="top.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="top.Show.showAR( this, 'defref_ions_RevenueFromContractWithCustomerNumberOfNewPerformanceObligations', window );">Number of new performance obligations | PerformanceObligation</a></td>
<td class="nump">1<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_RevenueFromContractWithCustomerTransactionPrice', window );">Transaction price</a></td>
<td class="nump">$ 64,900<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementAmendedInFebruary2017WithBayerMember', window );">Bayer [Member] | R&amp;D Services for IONIS-FXI-L [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="top.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="top.Show.showAR( this, 'defref_ions_RevenueFromContractWithCustomerNumberOfNewPerformanceObligations', window );">Number of new performance obligations | PerformanceObligation</a></td>
<td class="nump">1<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</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_MaximumAmountOfPaymentsReceivableForCommercializationMilestones">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The maximum amount of payments receivable for commercialization milestones under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MaximumAmountOfPaymentsReceivableForCommercializationMilestones</td>
</tr>
<tr>
<td style="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_MaximumAmountOfPaymentsReceivableForDevelopmentMilestones">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The maximum amount of payments receivable for development milestones under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MaximumAmountOfPaymentsReceivableForDevelopmentMilestones</td>
</tr>
<tr>
<td style="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_MaximumAmountOfPaymentsReceivableForLicenseFeesAndMilestones">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Maximum amount of payments receivable for license fees and milestone payments under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MaximumAmountOfPaymentsReceivableForLicenseFeesAndMilestones</td>
</tr>
<tr>
<td style="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_NextPotentialPayment">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The next potential payment to be earned under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_NextPotentialPayment</td>
</tr>
<tr>
<td style="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_PaymentReceivedForAdvancingPrograms">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The amount of payments received during the period for advancing programs under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_PaymentReceivedForAdvancingPrograms</td>
</tr>
<tr>
<td style="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_RevenueFromContractWithCustomerNumberOfNewPerformanceObligations">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The number of new performance obligations identified under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_RevenueFromContractWithCustomerNumberOfNewPerformanceObligations</td>
</tr>
<tr>
<td style="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_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</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_RoyaltyPercentageReceivedOnGrossMarginsOfDrugsUnderCollaborationAgreement">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The royalty percentage received on gross margins of drug(s) under the collaborative arrangement.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_RoyaltyPercentageReceivedOnGrossMarginsOfDrugsUnderCollaborationAgreement</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>num: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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 42<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e9054-108599<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 275<br> -SubTopic 10<br> -Section 50<br> -Paragraph 18<br> -URI http://asc.fasb.org/extlink&amp;oid=99393423&amp;loc=d3e6351-108592<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 825<br> -SubTopic 10<br> -Section 50<br> -Paragraph 20<br> -URI http://asc.fasb.org/extlink&amp;oid=121572278&amp;loc=d3e13531-108611<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 825<br> -SubTopic 10<br> -Section 50<br> -Paragraph 21<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=121572278&amp;loc=d3e13537-108611<br><br>Reference 5: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 275<br> -SubTopic 10<br> -Section 50<br> -Paragraph 20<br> -URI http://asc.fasb.org/extlink&amp;oid=99393423&amp;loc=d3e6404-108592<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>num: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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 45<br> -Paragraph 1<br> -URI http://asc.fasb.org/extlink&amp;oid=121556615&amp;loc=SL49130531-203044<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 50<br> -Paragraph 8<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=121604090&amp;loc=SL49130549-203045<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 45<br> -Paragraph 2<br> -URI http://asc.fasb.org/extlink&amp;oid=121556615&amp;loc=SL49130532-203044<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 30<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e8906-108599<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 40<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e9031-108599<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 41<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e9038-108599<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e8933-108599<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e8933-108599<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=121604090&amp;loc=SL49130543-203045<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 22<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e8736-108599<br><br>Reference 8: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 22<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e8736-108599<br><br>Reference 9: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 42<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e9054-108599<br><br>Reference 10: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 50<br> -Paragraph 5<br> -URI http://asc.fasb.org/extlink&amp;oid=121604090&amp;loc=SL49130545-203045<br><br>Reference 11: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 924<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 11.L)<br> -URI http://asc.fasb.org/extlink&amp;oid=6472922&amp;loc=d3e499488-122856<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember</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_CollaborativeArrangementsAndLicensingAgreementsBayerMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
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<span style="display: none;">v3.20.4</span><table class="report" border="0" cellspacing="2" id="idm140142731201352">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Collaborative Arrangements and Licensing Agreements, GSK (Details)<br> $ in Thousands</strong></div></th>
<th class="th" colspan="1">1 Months Ended</th>
<th class="th" colspan="1">3 Months Ended</th>
<th class="th" colspan="3">12 Months Ended</th>
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<tr>
<th class="th">
<div>Mar. 31, 2010 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Sep. 30, 2019 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Dec. 31, 2020 </div>
<div>USD ($) </div>
<div>Medicine</div>
</th>
<th class="th">
<div>Dec. 31, 2019 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Dec. 31, 2018 </div>
<div>USD ($)</div>
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<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 729,264<span></span>
</td>
<td class="nump">$ 1,122,599<span></span>
</td>
<td class="nump">$ 599,674<span></span>
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<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_srt_ProductOrServiceAxis=ions_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember', window );">R&amp;D Revenue [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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>
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<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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">$ 364,565<span></span>
</td>
<td class="nump">770,149<span></span>
</td>
<td class="nump">$ 344,752<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGlaxoSmithKlineMember', window );">GSK [Member]</a></td>
<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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>
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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="top.Show.showAR( this, 'defref_ions_UpfrontPaymentReceived', window );">Upfront payment received</a></td>
<td class="nump">$ 35,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
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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="top.Show.showAR( this, 'defref_ions_NumberOfMedicinesBeingDeveloped', window );">Number of medicines currently being developed | Medicine</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">2<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_MaximumAmountOfPaymentsReceivableForLicenseFeesAndMilestones', window );">Maximum amount of payments receivable for license fees and milestones</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 262,000<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="top.Show.showAR( this, 'defref_ions_MaximumAmountOfPaymentsReceivableForDevelopmentMilestones', window );">Maximum amount of payments receivable for development milestones</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">47,500<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_MaximumAmountOfPaymentsReceivableForRegulatoryMilestones', window );">Maximum amount of payments receivable for regulatory milestones</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">120,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_MaximumAmountOfPaymentsReceivableForCommercializationMilestones', window );">Maximum amount of payments receivable for commercialization milestones</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">70,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_NextPotentialPayment', window );">Next prospective payment</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">15,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 25,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
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<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ContractWithCustomerLiability', window );">Deferred revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 0<span></span>
</td>
<td class="nump">$ 0<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGlaxoSmithKlineMember', window );">GSK [Member] | Revenue [Member] | Strategic Partner [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="top.Show.showAR( this, 'defref_us-gaap_ConcentrationRiskPercentage1', window );">Concentration percentage</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">0.00%<span></span>
</td>
<td class="nump">2.00%<span></span>
</td>
<td class="nump">0.00%<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGlaxoSmithKlineMember', 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>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="top.Show.showAR( this, 'defref_ions_CumulativePaymentsReceived', window );">Cumulative payments received</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 190,000<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="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGlaxoSmithKlineMember', window );">GSK [Member] | R&amp;D Revenue [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 200<span></span>
</td>
<td class="nump">$ 25,400<span></span>
</td>
<td class="nump">$ 1,600<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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</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_MaximumAmountOfPaymentsReceivableForCommercializationMilestones">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The maximum amount of payments receivable for commercialization milestones under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MaximumAmountOfPaymentsReceivableForCommercializationMilestones</td>
</tr>
<tr>
<td style="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_MaximumAmountOfPaymentsReceivableForDevelopmentMilestones">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The maximum amount of payments receivable for development milestones under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MaximumAmountOfPaymentsReceivableForDevelopmentMilestones</td>
</tr>
<tr>
<td style="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_MaximumAmountOfPaymentsReceivableForLicenseFeesAndMilestones">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Maximum amount of payments receivable for license fees and milestone payments under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MaximumAmountOfPaymentsReceivableForLicenseFeesAndMilestones</td>
</tr>
<tr>
<td style="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_MaximumAmountOfPaymentsReceivableForRegulatoryMilestones">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The maximum amount of payments receivable for regulatory milestones under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MaximumAmountOfPaymentsReceivableForRegulatoryMilestones</td>
</tr>
<tr>
<td style="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_NextPotentialPayment">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The next potential payment to be earned under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_NextPotentialPayment</td>
</tr>
<tr>
<td style="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_NumberOfMedicinesBeingDeveloped">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The number of medicines currently being developed under the collaboration agreement(s).</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_NumberOfMedicinesBeingDeveloped</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:integerItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_UpfrontPaymentReceived">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 42<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e9054-108599<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 275<br> -SubTopic 10<br> -Section 50<br> -Paragraph 18<br> -URI http://asc.fasb.org/extlink&amp;oid=99393423&amp;loc=d3e6351-108592<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 825<br> -SubTopic 10<br> -Section 50<br> -Paragraph 20<br> -URI http://asc.fasb.org/extlink&amp;oid=121572278&amp;loc=d3e13531-108611<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 825<br> -SubTopic 10<br> -Section 50<br> -Paragraph 21<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=121572278&amp;loc=d3e13537-108611<br><br>Reference 5: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 275<br> -SubTopic 10<br> -Section 50<br> -Paragraph 20<br> -URI http://asc.fasb.org/extlink&amp;oid=99393423&amp;loc=d3e6404-108592<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>num: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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 45<br> -Paragraph 1<br> -URI http://asc.fasb.org/extlink&amp;oid=121556615&amp;loc=SL49130531-203044<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 50<br> -Paragraph 8<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=121604090&amp;loc=SL49130549-203045<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 45<br> -Paragraph 2<br> -URI http://asc.fasb.org/extlink&amp;oid=121556615&amp;loc=SL49130532-203044<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 30<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e8906-108599<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 40<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e9031-108599<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 41<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e9038-108599<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e8933-108599<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e8933-108599<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=121604090&amp;loc=SL49130543-203045<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 22<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e8736-108599<br><br>Reference 8: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 22<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e8736-108599<br><br>Reference 9: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 42<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e9054-108599<br><br>Reference 10: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 50<br> -Paragraph 5<br> -URI http://asc.fasb.org/extlink&amp;oid=121604090&amp;loc=SL49130545-203045<br><br>Reference 11: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 924<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 11.L)<br> -URI http://asc.fasb.org/extlink&amp;oid=6472922&amp;loc=d3e499488-122856<br></p></div>
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<span style="display: none;">v3.20.4</span><table class="report" border="0" cellspacing="2" id="idm140142735661352">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Collaborative Arrangements and Licensing Agreements, Janssen Biotech, Inc. (Details)<br> $ in Thousands</strong></div></th>
<th class="th" colspan="1">1 Months Ended</th>
<th class="th" colspan="1">3 Months Ended</th>
<th class="th" colspan="3">12 Months Ended</th>
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<tr>
<th class="th">
<div>Dec. 31, 2014 </div>
<div>USD ($) </div>
<div>PerformanceObligation</div>
</th>
<th class="th">
<div>Sep. 30, 2020 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Dec. 31, 2020 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Dec. 31, 2019 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Dec. 31, 2018 </div>
<div>USD ($)</div>
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<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="nump">$ 729,264<span></span>
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<td class="nump">$ 1,122,599<span></span>
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<td class="nump">$ 599,674<span></span>
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<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_srt_ProductOrServiceAxis=ions_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember', 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>
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<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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>
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<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="top.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">364,565<span></span>
</td>
<td class="nump">770,149<span></span>
</td>
<td class="nump">$ 344,752<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="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2014WithJanssenBiotechIncMember', window );">Janssen Biotech, Inc. [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="top.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>
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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="top.Show.showAR( this, 'defref_ions_UpfrontPaymentReceived', window );">Upfront payment received</a></td>
<td class="nump">$ 35,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
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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="top.Show.showAR( this, 'defref_ions_MinimumAmountOfPaymentsReceivableForLicenseFeesAndSubstantiveMilestones', window );">Minimum amount of payments receivable for license fees and milestones</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">285,000<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="top.Show.showAR( this, 'defref_ions_MaximumAmountOfPaymentsReceivableForDevelopmentMilestones', window );">Maximum amount of payments receivable for development milestones</a></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>
<td class="text">&#160;<span></span>
</td>
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<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_MaximumAmountOfPaymentsReceivableForRegulatoryMilestones', window );">Maximum amount of payments receivable for regulatory milestones</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">160,000<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="top.Show.showAR( this, 'defref_ions_MaximumAmountOfPaymentsReceivableForCommercializationMilestones', window );">Maximum amount of payments receivable for commercialization milestones</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">60,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
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<tr class="re">
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<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 custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations', window );">Number of separate performance obligations | PerformanceObligation</a></td>
<td class="nump">1<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_RevenueFromContractWithCustomerTransactionPrice', window );">Transaction price</a></td>
<td class="nump">$ 35,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
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<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 5,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
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<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ContractWithCustomerLiability', window );">Deferred revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 0<span></span>
</td>
<td class="nump">$ 0<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
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<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2014WithJanssenBiotechIncMember', window );">Janssen Biotech, Inc. [Member] | Revenue [Member] | Strategic Partner [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="top.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="nump">0.00%<span></span>
</td>
<td class="nump">1.00%<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2014WithJanssenBiotechIncMember', window );">Janssen Biotech, Inc. [Member] | Minimum [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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 custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_CumulativePaymentsReceived', window );">Cumulative payments received</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 80,000<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="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2014WithJanssenBiotechIncMember', window );">Janssen Biotech, Inc. [Member] | R&amp;D Revenue [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="top.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">$ 5,000<span></span>
</td>
<td class="nump">$ 100<span></span>
</td>
<td class="nump">$ 6,600<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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</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_MaximumAmountOfPaymentsReceivableForCommercializationMilestones">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The maximum amount of payments receivable for commercialization milestones under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MaximumAmountOfPaymentsReceivableForCommercializationMilestones</td>
</tr>
<tr>
<td style="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_MaximumAmountOfPaymentsReceivableForDevelopmentMilestones">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The maximum amount of payments receivable for development milestones under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MaximumAmountOfPaymentsReceivableForDevelopmentMilestones</td>
</tr>
<tr>
<td style="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_MaximumAmountOfPaymentsReceivableForRegulatoryMilestones">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The maximum amount of payments receivable for regulatory milestones under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MaximumAmountOfPaymentsReceivableForRegulatoryMilestones</td>
</tr>
<tr>
<td style="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_MinimumAmountOfPaymentsReceivableForLicenseFeesAndSubstantiveMilestones">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The minimum amount of payments receivable for license fees and substantive milestones under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MinimumAmountOfPaymentsReceivableForLicenseFeesAndSubstantiveMilestones</td>
</tr>
<tr>
<td style="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_NextPotentialPayment">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The next potential payment to be earned under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_NextPotentialPayment</td>
</tr>
<tr>
<td style="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_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</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_UpfrontPaymentReceived">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 42<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e9054-108599<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 275<br> -SubTopic 10<br> -Section 50<br> -Paragraph 18<br> -URI http://asc.fasb.org/extlink&amp;oid=99393423&amp;loc=d3e6351-108592<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 825<br> -SubTopic 10<br> -Section 50<br> -Paragraph 20<br> -URI http://asc.fasb.org/extlink&amp;oid=121572278&amp;loc=d3e13531-108611<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 825<br> -SubTopic 10<br> -Section 50<br> -Paragraph 21<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=121572278&amp;loc=d3e13537-108611<br><br>Reference 5: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 275<br> -SubTopic 10<br> -Section 50<br> -Paragraph 20<br> -URI http://asc.fasb.org/extlink&amp;oid=99393423&amp;loc=d3e6404-108592<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>num: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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 45<br> -Paragraph 1<br> -URI http://asc.fasb.org/extlink&amp;oid=121556615&amp;loc=SL49130531-203044<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 50<br> -Paragraph 8<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=121604090&amp;loc=SL49130549-203045<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 45<br> -Paragraph 2<br> -URI http://asc.fasb.org/extlink&amp;oid=121556615&amp;loc=SL49130532-203044<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>
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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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 30<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e8906-108599<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 40<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e9031-108599<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 41<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e9038-108599<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e8933-108599<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e8933-108599<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=121604090&amp;loc=SL49130543-203045<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 22<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e8736-108599<br><br>Reference 8: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 22<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e8736-108599<br><br>Reference 9: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 42<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e9054-108599<br><br>Reference 10: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 50<br> -Paragraph 5<br> -URI http://asc.fasb.org/extlink&amp;oid=121604090&amp;loc=SL49130545-203045<br><br>Reference 11: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 924<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 11.L)<br> -URI http://asc.fasb.org/extlink&amp;oid=6472922&amp;loc=d3e499488-122856<br></p></div>
<a href="javascript:void(0);" onclick="top.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="top.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_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<td><strong> Period Type:</strong></td>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
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<a href="javascript:void(0);" onclick="top.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="top.Show.hideAR();">X</a></td></tr>
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<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
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<span style="display: none;">v3.20.4</span><table class="report" border="0" cellspacing="2" id="idm140142740029256">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Collaborative Arrangements and Licensing Agreements, Novartis (Details)<br> $ in Thousands, shares in Millions</strong></div></th>
<th class="th" colspan="3">3 Months Ended</th>
<th class="th" colspan="3">12 Months Ended</th>
</tr>
<tr>
<th class="th">
<div>Mar. 31, 2019 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Jun. 30, 2017 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Mar. 31, 2017 </div>
<div>USD ($) </div>
<div>PerformanceObligation </div>
<div>shares</div>
</th>
<th class="th">
<div>Dec. 31, 2020 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Dec. 31, 2019 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Dec. 31, 2018 </div>
<div>USD ($)</div>
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<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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>
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<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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">$ 729,264<span></span>
</td>
<td class="nump">$ 1,122,599<span></span>
</td>
<td class="nump">$ 599,674<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="top.Show.showAR( this, 'defref_srt_ProductOrServiceAxis=ions_LicensingAndOtherRoyaltiesMember', window );">Licensing and Other 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>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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>
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<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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">8,117<span></span>
</td>
<td class="nump">17,205<span></span>
</td>
<td class="nump">14,755<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_srt_ProductOrServiceAxis=ions_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember', window );">R&amp;D Revenue [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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>
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<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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">364,565<span></span>
</td>
<td class="nump">770,149<span></span>
</td>
<td class="nump">$ 344,752<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember', window );">Novartis [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="top.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">$ 75,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_MaximumAmountOfPaymentsReceivableForMilestones', window );">Maximum amount of payments receivable for milestones</a></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">675,000<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="top.Show.showAR( this, 'defref_ions_MaximumAmountOfPaymentsReceivableForDevelopmentMilestones', window );">Maximum amount of payments receivable for development milestones</a></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>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_MaximumAmountOfPaymentsReceivableForRegulatoryMilestones', window );">Maximum amount of payments receivable for regulatory milestones</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">290,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_MaximumAmountOfPaymentsReceivableForCommercializationMilestones', window );">Maximum amount of payments receivable for commercialization milestones</a></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">360,000<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="top.Show.showAR( this, 'defref_ions_CumulativePaymentsReceived', window );">Cumulative payments received</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 249,000<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="top.Show.showAR( this, 'defref_ions_RoyaltyPercentageReceivedOnSalesOfDrug', window );">Royalty percentage received on sales of drug</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">20.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_NextPotentialPayment', window );">Next prospective payment</a></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>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="nump">1.6<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="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>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_AdditionalAmountOfCommonStockRequiredToBePurchased', window );">Additional amount of common stock required to be purchased</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 50,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ProceedsFromIssuanceOfPrivatePlacement', window );">Proceeds from sale of common stock to Novartis in a private placement</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 50,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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="top.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">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>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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">$ 108,400<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="nump">28,400<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_PotentialPremiumReceivedIfCommonStockIsPurchasedInFuture', window );">Potential premium received if common stock is purchased in the future</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">5,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ContractWithCustomerLiability', window );">Deferred revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 0<span></span>
</td>
<td class="nump">$ 0<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember', window );">Novartis [Member] | Revenue [Member] | Strategic Partner [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="top.Show.showAR( this, 'defref_us-gaap_ConcentrationRiskPercentage1', window );">Concentration percentage</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">0.00%<span></span>
</td>
<td class="nump">17.00%<span></span>
</td>
<td class="nump">8.00%<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember', window );">Novartis [Member] | Licensing and Other 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>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></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="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember', window );">Novartis [Member] | R&amp;D Services for Pelacarsen [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="top.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">64,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember', window );">Novartis [Member] | R&amp;D Services for IONIS-APOCIII-L [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="top.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="top.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">40,100<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember', window );">Novartis [Member] | Pelacarsen API [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="top.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">1,500<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember', window );">Novartis [Member] | IONIS-APOCIII-L API [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="top.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">$ 2,800<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember', window );">Novartis [Member] | R&amp;D Revenue [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="top.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">$ 1,000<span></span>
</td>
<td class="nump">$ 187,400<span></span>
</td>
<td class="nump">$ 50,600<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_AdditionalAmountOfCommonStockRequiredToBePurchased">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The additional amount of common stock the collaboration partner is required to purchase under a Stock Purchase Agreement (SPA) in conjunction with the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_AdditionalAmountOfCommonStockRequiredToBePurchased</td>
</tr>
<tr>
<td style="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_CollaborativeArrangementAndLicensingAgreementAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</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_MaximumAmountOfPaymentsReceivableForCommercializationMilestones">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The maximum amount of payments receivable for commercialization milestones under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MaximumAmountOfPaymentsReceivableForCommercializationMilestones</td>
</tr>
<tr>
<td style="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_MaximumAmountOfPaymentsReceivableForDevelopmentMilestones">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The maximum amount of payments receivable for development milestones under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MaximumAmountOfPaymentsReceivableForDevelopmentMilestones</td>
</tr>
<tr>
<td style="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_MaximumAmountOfPaymentsReceivableForMilestones">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The maximum amount of payments receivable for milestones under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MaximumAmountOfPaymentsReceivableForMilestones</td>
</tr>
<tr>
<td style="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_MaximumAmountOfPaymentsReceivableForRegulatoryMilestones">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The maximum amount of payments receivable for regulatory milestones under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MaximumAmountOfPaymentsReceivableForRegulatoryMilestones</td>
</tr>
<tr>
<td style="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_NextPotentialPayment">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The next potential payment to be earned under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_NextPotentialPayment</td>
</tr>
<tr>
<td style="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_PotentialPremiumReceivedIfCommonStockIsPurchasedInFuture">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The potential premium received if common stock is purchased in the future under a Stock Purchase Agreement (SPA) in conjunction with the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_PotentialPremiumReceivedIfCommonStockIsPurchasedInFuture</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_PremiumReceivedOnSharesIssued">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</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_RoyaltyPercentageReceivedOnSalesOfDrug">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Royalty percentage received on the sales of a drug by a collaboration partner under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_RoyaltyPercentageReceivedOnSalesOfDrug</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>num: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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 42<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e9054-108599<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 275<br> -SubTopic 10<br> -Section 50<br> -Paragraph 18<br> -URI http://asc.fasb.org/extlink&amp;oid=99393423&amp;loc=d3e6351-108592<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 825<br> -SubTopic 10<br> -Section 50<br> -Paragraph 20<br> -URI http://asc.fasb.org/extlink&amp;oid=121572278&amp;loc=d3e13531-108611<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 825<br> -SubTopic 10<br> -Section 50<br> -Paragraph 21<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=121572278&amp;loc=d3e13537-108611<br><br>Reference 5: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 275<br> -SubTopic 10<br> -Section 50<br> -Paragraph 20<br> -URI http://asc.fasb.org/extlink&amp;oid=99393423&amp;loc=d3e6404-108592<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>num: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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 45<br> -Paragraph 1<br> -URI http://asc.fasb.org/extlink&amp;oid=121556615&amp;loc=SL49130531-203044<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 50<br> -Paragraph 8<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=121604090&amp;loc=SL49130549-203045<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 45<br> -Paragraph 2<br> -URI http://asc.fasb.org/extlink&amp;oid=121556615&amp;loc=SL49130532-203044<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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_ProceedsFromIssuanceOfPrivatePlacement">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The cash inflow associated with the amount received from entity's raising of capital via private rather than public placement.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 14<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=121586364&amp;loc=d3e3255-108585<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ProceedsFromIssuanceOfPrivatePlacement</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>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_RevenueFromContractWithCustomerExcludingAssessedTax">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 30<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e8906-108599<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 40<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e9031-108599<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 41<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e9038-108599<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e8933-108599<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e8933-108599<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=121604090&amp;loc=SL49130543-203045<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 22<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e8736-108599<br><br>Reference 8: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 22<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e8736-108599<br><br>Reference 9: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 42<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e9054-108599<br><br>Reference 10: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 50<br> -Paragraph 5<br> -URI http://asc.fasb.org/extlink&amp;oid=121604090&amp;loc=SL49130545-203045<br><br>Reference 11: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 924<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 11.L)<br> -URI http://asc.fasb.org/extlink&amp;oid=6472922&amp;loc=d3e499488-122856<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_StockIssuedDuringPeriodSharesNewIssues">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Number of new stock issued during the period.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(29))<br> -URI http://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 505<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -URI http://asc.fasb.org/extlink&amp;oid=109259400&amp;loc=d3e21463-112644<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 505<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.3-04)<br> -URI http://asc.fasb.org/extlink&amp;oid=120397183&amp;loc=d3e187085-122770<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(28))<br> -URI http://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_StockIssuedDuringPeriodSharesNewIssues</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:sharesItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_srt_ProductOrServiceAxis=ions_LicensingAndOtherRoyaltiesMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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_LicensingAndOtherRoyaltiesMember</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_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember</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_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember</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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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_srt_ProductOrServiceAxis=ions_ResearchAndDevelopmentServicesForPelacarsenMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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_ResearchAndDevelopmentServicesForPelacarsenMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
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<td><strong> Data Type:</strong></td>
<td>na</td>
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<td><strong> Balance Type:</strong></td>
<td></td>
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<td></td>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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_ResearchAndDevelopmentServicesForIonisApociiiLMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
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<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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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_PelacarsenActivePharmaceuticalIngredientMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
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<tr>
<td><strong> Period Type:</strong></td>
<td></td>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_srt_ProductOrServiceAxis=ions_IonisApociiiLActivePharmaceuticalIngredientMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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_IonisApociiiLActivePharmaceuticalIngredientMember</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>
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<tr>
<td><strong> Period Type:</strong></td>
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<span style="display: none;">v3.20.4</span><table class="report" border="0" cellspacing="2" id="idm140142741388152">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Collaborative Arrangements and Licensing Agreements, Pfizer (Details)<br> $ in Thousands</strong></div></th>
<th class="th" colspan="1">1 Months Ended</th>
<th class="th" colspan="2">3 Months Ended</th>
<th class="th" colspan="3">12 Months Ended</th>
</tr>
<tr>
<th class="th">
<div>Oct. 31, 2019 </div>
<div>USD ($) </div>
<div>PerformanceObligation</div>
</th>
<th class="th">
<div>Dec. 31, 2020 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Dec. 31, 2019 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Dec. 31, 2020 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Dec. 31, 2019 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Dec. 31, 2018 </div>
<div>USD ($)</div>
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<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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>
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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="nump">$ 729,264<span></span>
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<td class="nump">$ 1,122,599<span></span>
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<td class="nump">$ 599,674<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="top.Show.showAR( this, 'defref_srt_ProductOrServiceAxis=ions_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember', window );">R&amp;D Revenue [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="top.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">364,565<span></span>
</td>
<td class="nump">770,149<span></span>
</td>
<td class="nump">$ 344,752<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2019WithPfizerMember', window );">Pfizer [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="top.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="top.Show.showAR( this, 'defref_ions_UpfrontPaymentReceived', window );">Upfront payment received</a></td>
<td class="nump">$ 250,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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="top.Show.showAR( this, 'defref_ions_MaximumAmountOfPaymentsReceivableForDevelopmentRegulatoryAndSalesMilestones', window );">Maximum amount of payments receivable for development, regulatory and sales milestones</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 1,300,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">1,300,000<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="top.Show.showAR( this, 'defref_ions_MaximumAmountOfPaymentsReceivableForDevelopmentMilestones', window );">Maximum amount of payments receivable for development milestones</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">205,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">205,000<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="top.Show.showAR( this, 'defref_ions_MaximumAmountOfPaymentsReceivableForRegulatoryMilestones', window );">Maximum amount of payments receivable for regulatory milestones</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">250,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">250,000<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="top.Show.showAR( this, 'defref_ions_MaximumAmountOfPaymentsReceivableForCommercializationMilestones', window );">Maximum amount of payments receivable for commercialization milestones</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">850,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 850,000<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="top.Show.showAR( this, 'defref_ions_RoyaltyPercentageReceivedOnNetSalesOfDrug', window );">Royalty percentage received on net sales of drug</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">20.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_NextPotentialPayment', window );">Next prospective payment</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">50,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 50,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations', window );">Number of separate performance obligations | PerformanceObligation</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>
<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="top.Show.showAR( this, 'defref_ions_RevenueFromContractWithCustomerTransactionPrice', window );">Transaction price</a></td>
<td class="nump">$ 250,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">75,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ContractWithCustomerLiability', window );">Deferred revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">$ 1,300<span></span>
</td>
<td class="nump">$ 0<span></span>
</td>
<td class="nump">$ 1,300<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="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2019WithPfizerMember', window );">Pfizer [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="top.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="top.Show.showAR( this, 'defref_us-gaap_ConcentrationRiskPercentage1', window );">Concentration percentage</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">11.00%<span></span>
</td>
<td class="nump">22.00%<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="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2019WithPfizerMember', window );">Pfizer [Member] | Minimum [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="top.Show.showAR( this, 'defref_ions_CumulativePaymentsReceived', window );">Cumulative payments received</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 330,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 330,000<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="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2019WithPfizerMember', window );">Pfizer [Member] | Vupanorsen [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="top.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="top.Show.showAR( this, 'defref_ions_RevenueFromContractWithCustomerTransactionPrice', window );">Transaction price</a></td>
<td class="nump">245,600<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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">$ 245,600<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2019WithPfizerMember', window );">Pfizer [Member] | R&amp;D Services for Vupanorsen [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="top.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="top.Show.showAR( this, 'defref_ions_RevenueFromContractWithCustomerTransactionPrice', window );">Transaction price</a></td>
<td class="nump">2,200<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>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2019WithPfizerMember', window );">Pfizer [Member] | Vupanorsen API [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="top.Show.showAR( this, 'defref_ions_RevenueFromContractWithCustomerTransactionPrice', window );">Transaction price</a></td>
<td class="nump">$ 2,200<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>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2019WithPfizerMember', window );">Pfizer [Member] | R&amp;D Revenue [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="top.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">$ 82,100<span></span>
</td>
<td class="nump">$ 248,700<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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
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<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</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_MaximumAmountOfPaymentsReceivableForCommercializationMilestones">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The maximum amount of payments receivable for commercialization milestones under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MaximumAmountOfPaymentsReceivableForCommercializationMilestones</td>
</tr>
<tr>
<td style="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_MaximumAmountOfPaymentsReceivableForDevelopmentMilestones">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The maximum amount of payments receivable for development milestones under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MaximumAmountOfPaymentsReceivableForDevelopmentMilestones</td>
</tr>
<tr>
<td style="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_MaximumAmountOfPaymentsReceivableForDevelopmentRegulatoryAndSalesMilestones">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The maximum amount of payments receivable for development, regulatory and sales milestones under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MaximumAmountOfPaymentsReceivableForDevelopmentRegulatoryAndSalesMilestones</td>
</tr>
<tr>
<td style="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_MaximumAmountOfPaymentsReceivableForRegulatoryMilestones">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The maximum amount of payments receivable for regulatory milestones under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MaximumAmountOfPaymentsReceivableForRegulatoryMilestones</td>
</tr>
<tr>
<td style="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_NextPotentialPayment">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The next potential payment to be earned under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_NextPotentialPayment</td>
</tr>
<tr>
<td style="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_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</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_RoyaltyPercentageReceivedOnNetSalesOfDrug">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Royalty percentage received on the net sales of a drug by a collaboration partner under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_RoyaltyPercentageReceivedOnNetSalesOfDrug</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>num: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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 42<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e9054-108599<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 275<br> -SubTopic 10<br> -Section 50<br> -Paragraph 18<br> -URI http://asc.fasb.org/extlink&amp;oid=99393423&amp;loc=d3e6351-108592<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 825<br> -SubTopic 10<br> -Section 50<br> -Paragraph 20<br> -URI http://asc.fasb.org/extlink&amp;oid=121572278&amp;loc=d3e13531-108611<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 825<br> -SubTopic 10<br> -Section 50<br> -Paragraph 21<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=121572278&amp;loc=d3e13537-108611<br><br>Reference 5: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 275<br> -SubTopic 10<br> -Section 50<br> -Paragraph 20<br> -URI http://asc.fasb.org/extlink&amp;oid=99393423&amp;loc=d3e6404-108592<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>num: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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 45<br> -Paragraph 1<br> -URI http://asc.fasb.org/extlink&amp;oid=121556615&amp;loc=SL49130531-203044<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 50<br> -Paragraph 8<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=121604090&amp;loc=SL49130549-203045<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 45<br> -Paragraph 2<br> -URI http://asc.fasb.org/extlink&amp;oid=121556615&amp;loc=SL49130532-203044<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 30<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e8906-108599<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 40<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e9031-108599<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 41<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e9038-108599<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e8933-108599<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e8933-108599<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=121604090&amp;loc=SL49130543-203045<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 22<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e8736-108599<br><br>Reference 8: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 22<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e8736-108599<br><br>Reference 9: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 42<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e9054-108599<br><br>Reference 10: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 50<br> -Paragraph 5<br> -URI http://asc.fasb.org/extlink&amp;oid=121604090&amp;loc=SL49130545-203045<br><br>Reference 11: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 924<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 11.L)<br> -URI http://asc.fasb.org/extlink&amp;oid=6472922&amp;loc=d3e499488-122856<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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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</div></td></tr>
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<a href="javascript:void(0);" onclick="top.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_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember</td>
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<tr>
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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> $ in Thousands</strong></div></th>
<th class="th" colspan="3">3 Months Ended</th>
<th class="th" colspan="3">12 Months Ended</th>
<th class="th" colspan="1"></th>
</tr>
<tr>
<th class="th">
<div>Dec. 31, 2019 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Jun. 30, 2019 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Sep. 30, 2018 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Dec. 31, 2020 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Dec. 31, 2019 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Dec. 31, 2018 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Aug. 31, 2018 </div>
<div>PerformanceObligation</div>
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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="top.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>
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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="nump">$ 729,264<span></span>
</td>
<td class="nump">$ 1,122,599<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>
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<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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>
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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="nump">8,117<span></span>
</td>
<td class="nump">17,205<span></span>
</td>
<td class="nump">$ 14,755<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>
</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="top.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>
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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">26,000<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="nump">$ 22,000<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>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="nump">20.00%<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>
<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>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_RevenueRecognizedByCollaborationPartnerInLatinAmericaBeforePayingRoyalties', window );">Minimum revenue recognized in Latin America by PTC before paying royalties</a></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>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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">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="top.Show.showAR( this, 'defref_us-gaap_ContractWithCustomerLiability', window );">Deferred revenue</a></td>
<td class="nump">$ 0<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 0<span></span>
</td>
<td class="nump">$ 0<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInAugust2018WithPtcTherapeuticsMember', window );">PTC Therapeutics [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="top.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="top.Show.showAR( this, 'defref_us-gaap_ConcentrationRiskPercentage1', window );">Concentration percentage</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">0.00%<span></span>
</td>
<td class="nump">1.00%<span></span>
</td>
<td class="nump">2.00%<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="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInAugust2018WithPtcTherapeuticsMember', window );">PTC Therapeutics [Member] | 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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="top.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">$ 12,000<span></span>
</td>
<td class="nump">$ 1,600<span></span>
</td>
<td class="nump">$ 10,200<span></span>
</td>
<td class="nump">$ 12,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInAugust2018WithPtcTherapeuticsMember', window );">PTC Therapeutics [Member] | WAYLIVRA [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="top.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="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 6,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInAugust2018WithPtcTherapeuticsMember', window );">PTC Therapeutics [Member] | TEGSEDI [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="top.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="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">$ 4,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</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_MaximumPaymentReceivableUnderLicenseAgreement">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The maximum amount of payments expected to be received under the license agreement.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MaximumPaymentReceivableUnderLicenseAgreement</td>
</tr>
<tr>
<td style="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_PeriodBeforeCollaborationPartnerPaysRoyaltiesOnNetSalesOfProductAfterFirstCommercialSaleInBrazil">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Period of time before collaboration partner pays royalties on net sales of product after first commercial sale in Brazil, 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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_PeriodBeforeCollaborationPartnerPaysRoyaltiesOnNetSalesOfProductAfterFirstCommercialSaleInBrazil</td>
</tr>
<tr>
<td style="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_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</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_RevenueRecognizedByCollaborationPartnerInLatinAmericaBeforePayingRoyalties">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The minimum amount of revenue recognized in Latin America by the collaboration partner before paying royalties.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_RevenueRecognizedByCollaborationPartnerInLatinAmericaBeforePayingRoyalties</td>
</tr>
<tr>
<td style="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_RoyaltyPercentageReceivedOnNetSalesOfEachDrugInLatinAmericaFromCollaborationPartner">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Royalty percentage received on the net sales of each drug in Latin America from the collaboration partner under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_RoyaltyPercentageReceivedOnNetSalesOfEachDrugInLatinAmericaFromCollaborationPartner</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>num:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ConcentrationRiskPercentage1">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 42<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e9054-108599<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 275<br> -SubTopic 10<br> -Section 50<br> -Paragraph 18<br> -URI http://asc.fasb.org/extlink&amp;oid=99393423&amp;loc=d3e6351-108592<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 825<br> -SubTopic 10<br> -Section 50<br> -Paragraph 20<br> -URI http://asc.fasb.org/extlink&amp;oid=121572278&amp;loc=d3e13531-108611<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 825<br> -SubTopic 10<br> -Section 50<br> -Paragraph 21<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=121572278&amp;loc=d3e13537-108611<br><br>Reference 5: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 275<br> -SubTopic 10<br> -Section 50<br> -Paragraph 20<br> -URI http://asc.fasb.org/extlink&amp;oid=99393423&amp;loc=d3e6404-108592<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>
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<td><strong> Data Type:</strong></td>
<td>num:percentItemType</td>
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<td><strong> Balance Type:</strong></td>
<td>na</td>
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<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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>
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<a href="javascript:void(0);" onclick="top.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="top.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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<th class="th" colspan="1">1 Months Ended</th>
<th class="th" colspan="4">3 Months Ended</th>
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<div>USD ($) </div>
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<div>Dec. 31, 2020 </div>
<div>USD ($)</div>
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<th class="th">
<div>Mar. 31, 2019 </div>
<div>USD ($)</div>
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<th class="th">
<div>Dec. 31, 2018 </div>
<div>USD ($)</div>
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<div>USD ($)</div>
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<div>Dec. 31, 2020 </div>
<div>USD ($) </div>
<div>Indication</div>
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<div>Dec. 31, 2019 </div>
<div>USD ($)</div>
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<th class="th">
<div>Dec. 31, 2018 </div>
<div>USD ($)</div>
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<th class="th">
<div>Dec. 31, 2017 </div>
<div>USD ($)</div>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ContractWithCustomerLiability', window );">Deferred revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 47,200<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="nump">$ 47,200<span></span>
</td>
<td class="nump">$ 52,300<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementsAndLicensingAgreementsRocheMember', window );">Roche [Member] | Revenue [Member] | Strategic Partner [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ConcentrationRiskPercentage1', window );">Concentration percentage</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">1.00%<span></span>
</td>
<td class="nump">5.00%<span></span>
</td>
<td class="nump">1.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementsAndLicensingAgreementsRocheMember', window );">Roche [Member] | R&amp;D Revenue [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 5,900<span></span>
</td>
<td class="nump">$ 57,000<span></span>
</td>
<td class="nump">$ 8,300<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="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember', window );">Huntington's Disease [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_UpfrontPaymentReceived', window );">Upfront payment received</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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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="top.Show.showAR( this, 'defref_ions_MilestonePaymentsReceived', window );">Milestone 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">$ 3,000<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="top.Show.showAR( this, 'defref_ions_MaximumAmountOfPaymentsReceivableForLicenseFeesAndMilestones', window );">Maximum amount of payments receivable for license fees and milestones</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">365,000<span></span>
</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">365,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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="top.Show.showAR( this, 'defref_ions_MaximumAmountOfPaymentsReceivableForDevelopmentMilestones', window );">Maximum amount of payments receivable for development milestones</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">70,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="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="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_MaximumAmountOfPaymentsReceivableForRegulatoryMilestones', window );">Maximum amount of payments receivable for regulatory milestones</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">170,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="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="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_MaximumAmountOfPaymentsReceivableForCommercializationMilestones', window );">Maximum amount of payments receivable for commercialization milestones</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">80,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="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="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_MaximumAmountOfPaymentReceivableForEachAdditionalDrugDeveloped', window );">Maximum amount of payment receivable for each additional drug developed</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">136,500<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="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="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_CumulativePaymentsReceived', window );">Cumulative payments received</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">150,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="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="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_NextPotentialPayment', window );">Next prospective payment</a></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="nump">15,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations', window );">Number of separate performance obligations | PerformanceObligation</a></td>
<td class="nump">1<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_RevenueFromContractWithCustomerTransactionPrice', window );">Transaction price</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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="nump">$ 45,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember', window );">IONIS-FB-L for Complement-Mediated Diseases [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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">$ 75,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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="top.Show.showAR( this, 'defref_ions_MaximumAmountOfPaymentsReceivableForLicenseFeesAndMilestones', window );">Maximum amount of payments receivable for license fees and milestones</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">684,000<span></span>
</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">684,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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="top.Show.showAR( this, 'defref_ions_NextPotentialPayment', window );">Next prospective payment</a></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="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="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="nump">1<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="nump">$ 75,000<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="top.Show.showAR( this, 'defref_ions_NumberOfDiseaseIndications', window );">Number of disease indications | Indication</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">2<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_RoyaltyPercentageReceivedOnNetSalesOfDrug', window );">Royalty percentage received on net sales of drug</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">20.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="num">$ (9,200)<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="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember', window );">IONIS-FB-L for Complement-Mediated Diseases [Member] | GA [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_NumberOfDiseaseIndications', window );">Number of disease indications | Indication</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">1<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember', window );">IONIS-FB-L for Complement-Mediated Diseases [Member] | IgA Nephropathy [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_NumberOfDiseaseIndications', window );">Number of disease indications | Indication</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">1<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</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_MaximumAmountOfPaymentReceivableForEachAdditionalDrugDeveloped">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The maximum amount of payments receivable for each additional drug developed under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MaximumAmountOfPaymentReceivableForEachAdditionalDrugDeveloped</td>
</tr>
<tr>
<td style="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_MaximumAmountOfPaymentsReceivableForCommercializationMilestones">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The maximum amount of payments receivable for commercialization milestones under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MaximumAmountOfPaymentsReceivableForCommercializationMilestones</td>
</tr>
<tr>
<td style="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_MaximumAmountOfPaymentsReceivableForDevelopmentMilestones">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The maximum amount of payments receivable for development milestones under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MaximumAmountOfPaymentsReceivableForDevelopmentMilestones</td>
</tr>
<tr>
<td style="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_MaximumAmountOfPaymentsReceivableForLicenseFeesAndMilestones">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Maximum amount of payments receivable for license fees and milestone payments under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MaximumAmountOfPaymentsReceivableForLicenseFeesAndMilestones</td>
</tr>
<tr>
<td style="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_MaximumAmountOfPaymentsReceivableForRegulatoryMilestones">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The maximum amount of payments receivable for regulatory milestones under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MaximumAmountOfPaymentsReceivableForRegulatoryMilestones</td>
</tr>
<tr>
<td style="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_MilestonePaymentsReceived">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The amount of milestone payments received during the period under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MilestonePaymentsReceived</td>
</tr>
<tr>
<td style="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_NextPotentialPayment">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The next potential payment to be earned under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_NextPotentialPayment</td>
</tr>
<tr>
<td style="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_NumberOfDiseaseIndications">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</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>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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</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_RoyaltyPercentageReceivedOnNetSalesOfDrug">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Royalty percentage received on the net sales of a drug by a collaboration partner under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_RoyaltyPercentageReceivedOnNetSalesOfDrug</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>num: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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 42<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e9054-108599<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 275<br> -SubTopic 10<br> -Section 50<br> -Paragraph 18<br> -URI http://asc.fasb.org/extlink&amp;oid=99393423&amp;loc=d3e6351-108592<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 825<br> -SubTopic 10<br> -Section 50<br> -Paragraph 20<br> -URI http://asc.fasb.org/extlink&amp;oid=121572278&amp;loc=d3e13531-108611<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 825<br> -SubTopic 10<br> -Section 50<br> -Paragraph 21<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=121572278&amp;loc=d3e13537-108611<br><br>Reference 5: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 275<br> -SubTopic 10<br> -Section 50<br> -Paragraph 20<br> -URI http://asc.fasb.org/extlink&amp;oid=99393423&amp;loc=d3e6404-108592<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>num: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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 45<br> -Paragraph 1<br> -URI http://asc.fasb.org/extlink&amp;oid=121556615&amp;loc=SL49130531-203044<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 50<br> -Paragraph 8<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=121604090&amp;loc=SL49130549-203045<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 45<br> -Paragraph 2<br> -URI http://asc.fasb.org/extlink&amp;oid=121556615&amp;loc=SL49130532-203044<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 30<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e8906-108599<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 40<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e9031-108599<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 41<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e9038-108599<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e8933-108599<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e8933-108599<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=121604090&amp;loc=SL49130543-203045<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 22<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e8736-108599<br><br>Reference 8: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 22<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e8736-108599<br><br>Reference 9: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 42<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e9054-108599<br><br>Reference 10: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 50<br> -Paragraph 5<br> -URI http://asc.fasb.org/extlink&amp;oid=121604090&amp;loc=SL49130545-203045<br><br>Reference 11: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 924<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 11.L)<br> -URI http://asc.fasb.org/extlink&amp;oid=6472922&amp;loc=d3e499488-122856<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember</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_CollaborativeArrangementsAndLicensingAgreementsRocheMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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_CollaborativeArrangementsAndLicensingAgreementsRocheMember</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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember</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_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember</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_GeographicAtrophyMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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>
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<span style="display: none;">v3.20.4</span><table class="report" border="0" cellspacing="2" id="idm140142724380024">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Collaborative Arrangements and Licensing Agreements, Alnylam Pharmaceuticals, Inc. (Details) - USD ($)<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, 2020</div></th>
<th class="th"><div>Dec. 31, 2020</div></th>
<th class="th"><div>Dec. 31, 2019</div></th>
<th class="th"><div>Dec. 31, 2018</div></th>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 729,264<span></span>
</td>
<td class="nump">$ 1,122,599<span></span>
</td>
<td class="nump">$ 599,674<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_srt_ProductOrServiceAxis=ions_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember', 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="top.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="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">364,565<span></span>
</td>
<td class="nump">770,149<span></span>
</td>
<td class="nump">$ 344,752<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2004WithAlnylamPharmaceuticalsIncMember', 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="top.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="top.Show.showAR( this, 'defref_us-gaap_LitigationSettlementAmountAwardedFromOtherParty', window );">Award from arbitration panel</a></td>
<td class="nump">$ 41,200<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">41,200<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="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="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2004WithAlnylamPharmaceuticalsIncMember', 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="top.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="top.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="nump">2.00%<span></span>
</td>
<td class="nump">0.00%<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2004WithAlnylamPharmaceuticalsIncMember', 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="top.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="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 47,900<span></span>
</td>
<td class="nump">$ 24,100<span></span>
</td>
<td class="nump">$ 2,000<span></span>
</td>
</tr>
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<div style="display: none;">
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<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_CollaborativeArrangementAndLicensingAgreementAbstract</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
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<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
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<td><strong> Balance Type:</strong></td>
<td>na</td>
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<td><strong> Period Type:</strong></td>
<td>duration</td>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ConcentrationRiskPercentage1">
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<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 42<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e9054-108599<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 275<br> -SubTopic 10<br> -Section 50<br> -Paragraph 18<br> -URI http://asc.fasb.org/extlink&amp;oid=99393423&amp;loc=d3e6351-108592<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 825<br> -SubTopic 10<br> -Section 50<br> -Paragraph 20<br> -URI http://asc.fasb.org/extlink&amp;oid=121572278&amp;loc=d3e13531-108611<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 825<br> -SubTopic 10<br> -Section 50<br> -Paragraph 21<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=121572278&amp;loc=d3e13537-108611<br><br>Reference 5: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 275<br> -SubTopic 10<br> -Section 50<br> -Paragraph 20<br> -URI http://asc.fasb.org/extlink&amp;oid=99393423&amp;loc=d3e6404-108592<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>
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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_ContractWithCustomerLiability">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 45<br> -Paragraph 1<br> -URI http://asc.fasb.org/extlink&amp;oid=121556615&amp;loc=SL49130531-203044<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 50<br> -Paragraph 8<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=121604090&amp;loc=SL49130549-203045<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 45<br> -Paragraph 2<br> -URI http://asc.fasb.org/extlink&amp;oid=121556615&amp;loc=SL49130532-203044<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>
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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>instant</td>
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<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount awarded from other party in judgment or settlement of litigation.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
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<td><strong> Balance Type:</strong></td>
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<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 30<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e8906-108599<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 40<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e9031-108599<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 41<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e9038-108599<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e8933-108599<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e8933-108599<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=121604090&amp;loc=SL49130543-203045<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 22<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e8736-108599<br><br>Reference 8: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 22<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e8736-108599<br><br>Reference 9: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 42<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e9054-108599<br><br>Reference 10: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 50<br> -Paragraph 5<br> -URI http://asc.fasb.org/extlink&amp;oid=121604090&amp;loc=SL49130545-203045<br><br>Reference 11: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 924<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 11.L)<br> -URI http://asc.fasb.org/extlink&amp;oid=6472922&amp;loc=d3e499488-122856<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</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_srt_ProductOrServiceAxis=ions_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember</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>
<td></td>
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<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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2004WithAlnylamPharmaceuticalsIncMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
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<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
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<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ConcentrationRiskByBenchmarkAxis=us-gaap_RevenueFromContractWithCustomerMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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>
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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>
<td></td>
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<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="top.Show.hideAR();">X</a></td></tr>
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<a href="javascript:void(0);" onclick="top.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>
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<td></td>
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<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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<span style="display: none;">v3.20.4</span><table class="report" border="0" cellspacing="2" id="idm140142731201416">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Akcea Acquisition (Details) - USD ($)<br> $ / shares in Units, shares in Millions, $ in Millions</strong></div></th>
<th class="th" colspan="1">1 Months Ended</th>
<th class="th" colspan="1">3 Months Ended</th>
<th class="th" colspan="1"></th>
<th class="th" colspan="1"></th>
</tr>
<tr>
<th class="th"><div>Oct. 31, 2020</div></th>
<th class="th"><div>Dec. 31, 2020</div></th>
<th class="th"><div>Sep. 30, 2020</div></th>
<th class="th"><div>Jun. 30, 2017</div></th>
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<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RestructuringCostAndReserveAxis=ions_AkceaAcquisitionEmployeeSeveranceAndRetentionMember', window );">Severance and Retention Related to Akcea Acquisition [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="top.Show.showAR( this, 'defref_us-gaap_RestructuringCostsAbstract', window );"><strong>Severance and Retention Costs [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RestructuringReserve', window );">Beginning balance</a></td>
<td class="nump">$ 0.0<span></span>
</td>
<td class="nump">$ 0.0<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RestructuringCharges', window );">Severance and retention expense</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">15.3<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="top.Show.showAR( this, 'defref_us-gaap_PaymentsForRestructuring', window );">Amounts paid during the period</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="num">(0.6)<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="top.Show.showAR( this, 'defref_us-gaap_RestructuringCostAndReserveAxis=ions_AkceaAcquisitionEmployeeSeveranceAndRetentionMember', window );">Severance and Retention Related to Akcea Acquisition [Member] | Accrued Compensation [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="top.Show.showAR( this, 'defref_us-gaap_RestructuringCostsAbstract', window );"><strong>Severance and Retention Costs [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RestructuringReserve', window );">Ending balance</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">14.7<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="top.Show.showAR( this, 'defref_us-gaap_RestructuringCostAndReserveAxis=ions_AkceaAcquisitionEmployeeSeveranceAndRetentionMember', window );">Severance and Retention Related to Akcea Acquisition [Member] | R&amp;D Expenses [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="top.Show.showAR( this, 'defref_us-gaap_RestructuringCostsAbstract', window );"><strong>Severance and Retention Costs [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RestructuringCharges', window );">Severance and retention expense</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">3.9<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="top.Show.showAR( this, 'defref_us-gaap_RestructuringCostAndReserveAxis=ions_AkceaAcquisitionEmployeeSeveranceAndRetentionMember', window );">Severance and Retention Related to Akcea Acquisition [Member] | SG&amp;A Expenses [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="top.Show.showAR( this, 'defref_us-gaap_RestructuringCostsAbstract', window );"><strong>Severance and Retention Costs [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RestructuringCharges', window );">Severance and retention expense</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">11.4<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="top.Show.showAR( this, 'defref_us-gaap_RestructuringCostAndReserveAxis=ions_AkceaAcquisitionEmployeeSeveranceMember', window );">Severance Related to Akcea Acquisition [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="top.Show.showAR( this, 'defref_us-gaap_RestructuringCostsAbstract', window );"><strong>Severance and Retention Costs [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RestructuringAndRelatedCostExpectedCost1', window );">Expected expenses</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">9.3<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="top.Show.showAR( this, 'defref_us-gaap_RestructuringCostAndReserveAxis=ions_AkceaAcquisitionEmployeeRetentionMember', window );">Retention Related to Akcea Acquisition [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="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RestructuringCostsAbstract', window );"><strong>Severance and Retention Costs [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RestructuringAndRelatedCostExpectedCost1', window );">Expected expenses</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">19.2<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_srt_OwnershipAxis=ions_AkceaTherapeuticsIncMember', window );">Akcea [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ConsolidationLessThanWhollyOwnedSubsidiaryParentOwnershipInterestChangesNetAbstract', window );"><strong>Akcea Acquisition [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_MinorityInterestOwnershipPercentageByParent', window );">Percentage ownership</a></td>
<td class="nump">100.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">76.00%<span></span>
</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="top.Show.showAR( this, 'defref_ions_ConsolidationLessThanWhollyOwnedSubsidiaryParentOwnershipInterestChangesPurchaseOfInterestByParentShares', window );">Shares purchased (in shares)</a></td>
<td class="nump">24.8<span></span>
</td>
<td class="text">&#160;<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="top.Show.showAR( this, 'defref_ions_ConsolidationLessThanWhollyOwnedSubsidiaryParentOwnershipInterestChangesPurchaseOfInterestByParentPricePerShare', window );">Purchase price per share (in dollars per share)</a></td>
<td class="nump">$ 18.15<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ConsolidationLessThanWhollyOwnedSubsidiaryParentOwnershipInterestChangesPurchaseOfInterestByParent', window );">Purchase price</a></td>
<td class="nump">$ 450.6<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_BusinessAcquisitionCostOfAcquiredEntityTransactionCosts', window );">Direct transaction costs</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 40.6<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_CashPurchasePriceOfEquityAwards', window );">Cash purchase price of equity awards (in dollars per share)</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 18.15<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="top.Show.showAR( this, 'defref_ions_PaymentsForCancelledEquityAwards', window );">Payments for cancelled equity awards</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 53.4<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions', window );">Unrecognized compensation cost related to non-vested RSUs</a></td>
<td class="nump">$ 59.3<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_srt_OwnershipAxis=ions_AkceaTherapeuticsIncMember', window );">Akcea [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="top.Show.showAR( this, 'defref_us-gaap_ConsolidationLessThanWhollyOwnedSubsidiaryParentOwnershipInterestChangesNetAbstract', window );"><strong>Akcea Acquisition [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_MinorityInterestOwnershipPercentageByParent', window );">Percentage ownership</a></td>
<td class="nump">77.00%<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>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_CashPurchasePriceOfEquityAwards">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Cash purchase price for each equity award held, including stock options and restricted stock units (RSUs).</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_CashPurchasePriceOfEquityAwards</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>num: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_ConsolidationLessThanWhollyOwnedSubsidiaryParentOwnershipInterestChangesPurchaseOfInterestByParentPricePerShare">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Per share amount paid for the shares of the subsidiary purchased by the parent during the period, thereby effecting a change in total (consolidated) equity attributable to the parent.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_ConsolidationLessThanWhollyOwnedSubsidiaryParentOwnershipInterestChangesPurchaseOfInterestByParentPricePerShare</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>num: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_ConsolidationLessThanWhollyOwnedSubsidiaryParentOwnershipInterestChangesPurchaseOfInterestByParentShares">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Number of shares of the subsidiary purchased by the parent during the period, thereby effecting a change in total (consolidated) equity attributable to the parent.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_ConsolidationLessThanWhollyOwnedSubsidiaryParentOwnershipInterestChangesPurchaseOfInterestByParentShares</td>
</tr>
<tr>
<td style="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_PaymentsForCancelledEquityAwards">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The aggregate amount paid by the entity to cancel subsidiary's outstanding equity awards.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_PaymentsForCancelledEquityAwards</td>
</tr>
<tr>
<td style="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_BusinessAcquisitionCostOfAcquiredEntityTransactionCosts">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of direct costs of the business combination including legal, accounting, and other costs incurred to consummate the business acquisition.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_BusinessAcquisitionCostOfAcquiredEntityTransactionCosts</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>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_ConsolidationLessThanWhollyOwnedSubsidiaryParentOwnershipInterestChangesNetAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ConsolidationLessThanWhollyOwnedSubsidiaryParentOwnershipInterestChangesNetAbstract</td>
</tr>
<tr>
<td style="padding-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_ConsolidationLessThanWhollyOwnedSubsidiaryParentOwnershipInterestChangesPurchaseOfInterestByParent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Represents the purchase by the parent of an additional equity interest in a subsidiary during the period, thereby effecting a change in total (consolidated) equity attributable to the parent. The purchase of the additional equity interest represented by this element increases the parent's controlling interest in the subsidiary.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 505<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -URI http://asc.fasb.org/extlink&amp;oid=120397183&amp;loc=d3e187085-122770<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 810<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1A<br> -Subparagraph (d)<br> -URI http://asc.fasb.org/extlink&amp;oid=109239629&amp;loc=SL4573702-111684<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 810<br> -SubTopic 10<br> -Section 55<br> -Paragraph 4M<br> -URI http://asc.fasb.org/extlink&amp;oid=120409616&amp;loc=SL4591554-111686<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ConsolidationLessThanWhollyOwnedSubsidiaryParentOwnershipInterestChangesPurchaseOfInterestByParent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>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_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (i)<br> -URI http://asc.fasb.org/extlink&amp;oid=120381028&amp;loc=d3e5070-113901<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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_MinorityInterestOwnershipPercentageByParent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The parent entity's interest in net assets of the subsidiary, expressed as a percentage.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_MinorityInterestOwnershipPercentageByParent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>num: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_PaymentsForRestructuring">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of cash payments made as the result of exit or disposal activities. Excludes payments associated with a discontinued operation or an asset retirement obligation.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 420<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (b)(2)<br> -URI http://asc.fasb.org/extlink&amp;oid=6394359&amp;loc=d3e17939-110869<br><br>Reference 2: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 17<br> -Subparagraph (f)<br> -URI http://asc.fasb.org/extlink&amp;oid=121586364&amp;loc=d3e3367-108585<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PaymentsForRestructuring</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>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_RestructuringAndRelatedCostExpectedCost1">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount expected to be recognized in earnings for the specified restructuring cost.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 420<br> -SubTopic 10<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SAB Topic 5.P.4(b)(1))<br> -URI http://asc.fasb.org/extlink&amp;oid=115931487&amp;loc=d3e140904-122747<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 420<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (b)(1)<br> -URI http://asc.fasb.org/extlink&amp;oid=6394359&amp;loc=d3e17939-110869<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 420<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (d)<br> -URI http://asc.fasb.org/extlink&amp;oid=6394359&amp;loc=d3e17939-110869<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 420<br> -SubTopic 10<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SAB Topic 5.P.4(d))<br> -URI http://asc.fasb.org/extlink&amp;oid=115931487&amp;loc=d3e140904-122747<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_RestructuringAndRelatedCostExpectedCost1</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>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_RestructuringCharges">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of expenses associated with exit or disposal activities pursuant to an authorized plan. Excludes expenses related to a discontinued operation or an asset retirement obligation.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 420<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 5.P.3)<br> -URI http://asc.fasb.org/extlink&amp;oid=115931487&amp;loc=d3e140864-122747<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 420<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=6394359&amp;loc=d3e17939-110869<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=121586364&amp;loc=d3e3602-108585<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 420<br> -SubTopic 10<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SAB Topic 5.P.4(b))<br> -URI http://asc.fasb.org/extlink&amp;oid=115931487&amp;loc=d3e140904-122747<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_RestructuringCharges</td>
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<td><strong> Balance Type:</strong></td>
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<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_RestructuringCostsAbstract</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_RestructuringReserve">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Carrying amount (including both current and noncurrent portions of the accrual) as of the balance sheet date pertaining to a specified type of cost associated with exit from or disposal of business activities or restructuring pursuant to a duly authorized plan.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 420<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (b)(2)<br> -URI http://asc.fasb.org/extlink&amp;oid=6394359&amp;loc=d3e17939-110869<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 420<br> -SubTopic 10<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SAB TOPIC 5.P.4(b))<br> -URI http://asc.fasb.org/extlink&amp;oid=115931487&amp;loc=d3e140904-122747<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_RestructuringReserve</td>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
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<a href="javascript:void(0);" onclick="top.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_RestructuringCostAndReserveAxis=ions_AkceaAcquisitionEmployeeSeveranceAndRetentionMember</td>
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<td><strong> Data Type:</strong></td>
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<td><strong> Period Type:</strong></td>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<td><strong> Period Type:</strong></td>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_IncomeStatementLocationAxis=ions_ResearchAndDevelopmentExpensesMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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=ions_ResearchAndDevelopmentExpensesMember</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<td><strong> Data Type:</strong></td>
<td>na</td>
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<td><strong> Balance Type:</strong></td>
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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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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_SellingGeneralAndAdministrativeExpensesMember</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<td><strong> Data Type:</strong></td>
<td>na</td>
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<td><strong> Balance Type:</strong></td>
<td></td>
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<tr>
<td><strong> Period Type:</strong></td>
<td></td>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_RestructuringCostAndReserveAxis=ions_AkceaAcquisitionEmployeeSeveranceMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
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<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_RestructuringCostAndReserveAxis=ions_AkceaAcquisitionEmployeeSeveranceMember</td>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
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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="top.Show.hideAR();">X</a></td></tr>
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<a href="javascript:void(0);" onclick="top.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_RestructuringCostAndReserveAxis=ions_AkceaAcquisitionEmployeeRetentionMember</td>
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<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">srt_OwnershipAxis=ions_AkceaTherapeuticsIncMember</td>
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<span style="display: none;">v3.20.4</span><table class="report" border="0" cellspacing="2" id="idm140142740912008">
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<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Severance and Retention Costs related to our Restructured European Operations (Details) - Severance and Retention Related to Updated European Distribution Model [Member]<br> $ in Millions</strong></div></th>
<th class="th" colspan="1">3 Months Ended</th>
</tr>
<tr><th class="th">
<div>Dec. 31, 2020 </div>
<div>USD ($)</div>
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<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RestructuringCostsAbstract', window );"><strong>Severance and Retention Costs related to our Restructured European Operations [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
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<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RestructuringReserve', window );">Beginning balance</a></td>
<td class="nump">$ 0.0<span></span>
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<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RestructuringCharges', window );">Severance and retention expense</a></td>
<td class="nump">12.5<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_PaymentsForRestructuring', window );">Amounts paid during the period</a></td>
<td class="num">(0.1)<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="top.Show.showAR( this, 'defref_us-gaap_RestructuringCostAndReserveAxis=ions_UpdatedEuropeanDistributionModelEmployeeSeveranceAndRetentionMember', window );">Accrued Compensation [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="top.Show.showAR( this, 'defref_us-gaap_RestructuringCostsAbstract', window );"><strong>Severance and Retention Costs related to our Restructured European Operations [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="top.Show.showAR( this, 'defref_us-gaap_RestructuringReserve', window );">Ending balance</a></td>
<td class="nump">12.4<span></span>
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<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RestructuringCostAndReserveAxis=ions_UpdatedEuropeanDistributionModelEmployeeSeveranceAndRetentionMember', window );">R&amp;D Expenses [Member]</a></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="top.Show.showAR( this, 'defref_us-gaap_RestructuringCostsAbstract', window );"><strong>Severance and Retention Costs related to our Restructured European Operations [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="top.Show.showAR( this, 'defref_us-gaap_RestructuringCharges', window );">Severance and retention expense</a></td>
<td class="nump">4.2<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RestructuringCostAndReserveAxis=ions_UpdatedEuropeanDistributionModelEmployeeSeveranceAndRetentionMember', window );">SG&amp;A Expenses [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="top.Show.showAR( this, 'defref_us-gaap_RestructuringCostsAbstract', window );"><strong>Severance and Retention Costs related to our Restructured European Operations [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="top.Show.showAR( this, 'defref_us-gaap_RestructuringCharges', window );">Severance and retention expense</a></td>
<td class="nump">8.3<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RestructuringCostAndReserveAxis=ions_UpdatedEuropeanDistributionModelEmployeeSeveranceAndRetentionMember', window );">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="top.Show.showAR( this, 'defref_us-gaap_RestructuringCostsAbstract', window );"><strong>Severance and Retention Costs related to our Restructured European Operations [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="top.Show.showAR( this, 'defref_us-gaap_RestructuringAndRelatedCostExpectedCost1', window );">Expected expenses</a></td>
<td class="nump">$ 14.8<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_PaymentsForRestructuring">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of cash payments made as the result of exit or disposal activities. Excludes payments associated with a discontinued operation or an asset retirement obligation.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 420<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (b)(2)<br> -URI http://asc.fasb.org/extlink&amp;oid=6394359&amp;loc=d3e17939-110869<br><br>Reference 2: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 17<br> -Subparagraph (f)<br> -URI http://asc.fasb.org/extlink&amp;oid=121586364&amp;loc=d3e3367-108585<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PaymentsForRestructuring</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>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_RestructuringAndRelatedCostExpectedCost1">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount expected to be recognized in earnings for the specified restructuring cost.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 420<br> -SubTopic 10<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SAB Topic 5.P.4(b)(1))<br> -URI http://asc.fasb.org/extlink&amp;oid=115931487&amp;loc=d3e140904-122747<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 420<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (b)(1)<br> -URI http://asc.fasb.org/extlink&amp;oid=6394359&amp;loc=d3e17939-110869<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 420<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (d)<br> -URI http://asc.fasb.org/extlink&amp;oid=6394359&amp;loc=d3e17939-110869<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 420<br> -SubTopic 10<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SAB Topic 5.P.4(d))<br> -URI http://asc.fasb.org/extlink&amp;oid=115931487&amp;loc=d3e140904-122747<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_RestructuringAndRelatedCostExpectedCost1</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>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>
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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_RestructuringCharges">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of expenses associated with exit or disposal activities pursuant to an authorized plan. Excludes expenses related to a discontinued operation or an asset retirement obligation.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 420<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 5.P.3)<br> -URI http://asc.fasb.org/extlink&amp;oid=115931487&amp;loc=d3e140864-122747<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 420<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=6394359&amp;loc=d3e17939-110869<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=121586364&amp;loc=d3e3602-108585<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 420<br> -SubTopic 10<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SAB Topic 5.P.4(b))<br> -URI http://asc.fasb.org/extlink&amp;oid=115931487&amp;loc=d3e140904-122747<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_RestructuringCharges</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>
</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>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_RestructuringCostsAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_RestructuringCostsAbstract</td>
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<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
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<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
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<td><strong> Balance Type:</strong></td>
<td>na</td>
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<td><strong> Period Type:</strong></td>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_RestructuringReserve">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Carrying amount (including both current and noncurrent portions of the accrual) as of the balance sheet date pertaining to a specified type of cost associated with exit from or disposal of business activities or restructuring pursuant to a duly authorized plan.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 420<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (b)(2)<br> -URI http://asc.fasb.org/extlink&amp;oid=6394359&amp;loc=d3e17939-110869<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 420<br> -SubTopic 10<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SAB TOPIC 5.P.4(b))<br> -URI http://asc.fasb.org/extlink&amp;oid=115931487&amp;loc=d3e140904-122747<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_RestructuringReserve</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>instant</td>
</tr>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_RestructuringCostAndReserveAxis=ions_UpdatedEuropeanDistributionModelEmployeeSeveranceAndRetentionMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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_RestructuringCostAndReserveAxis=ions_UpdatedEuropeanDistributionModelEmployeeSeveranceAndRetentionMember</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_BalanceSheetLocationAxis=ions_EmployeeRelatedLiabilitiesCurrentMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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_BalanceSheetLocationAxis=ions_EmployeeRelatedLiabilitiesCurrentMember</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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<td><strong> Period Type:</strong></td>
<td></td>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_IncomeStatementLocationAxis=ions_ResearchAndDevelopmentExpensesMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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=ions_ResearchAndDevelopmentExpensesMember</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>
</tr>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_IncomeStatementLocationAxis=us-gaap_SellingGeneralAndAdministrativeExpensesMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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_SellingGeneralAndAdministrativeExpensesMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
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</div></td></tr>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_srt_RangeAxis=srt_MaximumMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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>
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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>
</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;">v3.20.4</span><table class="report" border="0" cellspacing="2" id="idm140142731700680">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Segment Information and Concentration of Business Risk, Segment Information (Details)<br> $ in Thousands</strong></div></th>
<th class="th" colspan="2">3 Months Ended</th>
<th class="th" colspan="3">12 Months Ended</th>
</tr>
<tr>
<th class="th">
<div>Dec. 31, 2020 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Dec. 31, 2019 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Dec. 31, 2020 </div>
<div>USD ($) </div>
<div>Segment</div>
</th>
<th class="th">
<div>Dec. 31, 2019 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Dec. 31, 2018 </div>
<div>USD ($)</div>
</th>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_SegmentReportingAbstract', window );"><strong>Segment Information and Concentration of Business Risk [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_NumberOfReportableSegments', window );">Number of reportable segments | Segment</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">2<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_SegmentReportingDisclosureOfEntitysReportableSegmentsAbstract', window );"><strong>Segment Information [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 729,264<span></span>
</td>
<td class="nump">$ 1,122,599<span></span>
</td>
<td class="nump">$ 599,674<span></span>
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<tr class="re">
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<td class="nump">$ 312,945<span></span>
</td>
<td class="nump">$ 233,028<span></span>
</td>
<td class="nump">901,346<span></span>
</td>
<td class="nump">756,716<span></span>
</td>
<td class="nump">661,046<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_OperatingIncomeLoss', window );">Income (loss) from operations</a></td>
<td class="num">(22,664)<span></span>
</td>
<td class="nump">260,652<span></span>
</td>
<td class="num">(172,082)<span></span>
</td>
<td class="nump">365,883<span></span>
</td>
<td class="num">(61,372)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_Assets', window );">Total assets</a></td>
<td class="nump">2,389,755<span></span>
</td>
<td class="nump">3,233,112<span></span>
</td>
<td class="nump">2,389,755<span></span>
</td>
<td class="nump">3,233,112<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_SegmentReportingDisclosureOfEntitysReportableSegmentsAbstract', window );"><strong>Segment Information [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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">364,699<span></span>
</td>
<td class="nump">352,450<span></span>
</td>
<td class="nump">254,922<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_SegmentReportingDisclosureOfEntitysReportableSegmentsAbstract', window );"><strong>Segment Information [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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">286,583<span></span>
</td>
<td class="nump">292,992<span></span>
</td>
<td class="nump">237,930<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_srt_ProductOrServiceAxis=us-gaap_ProductMember', window );">Product Sales, 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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_SegmentReportingDisclosureOfEntitysReportableSegmentsAbstract', window );"><strong>Segment Information [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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">69,999<span></span>
</td>
<td class="nump">42,253<span></span>
</td>
<td class="nump">2,237<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_SegmentReportingDisclosureOfEntitysReportableSegmentsAbstract', window );"><strong>Segment Information [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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">8,117<span></span>
</td>
<td class="nump">17,205<span></span>
</td>
<td class="nump">14,755<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_srt_ProductOrServiceAxis=ions_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember', window );">R&amp;D Revenue Under Collaborative 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>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_SegmentReportingDisclosureOfEntitysReportableSegmentsAbstract', window );"><strong>Segment Information [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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">364,565<span></span>
</td>
<td class="nump">770,149<span></span>
</td>
<td class="nump">344,752<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_srt_ConsolidationItemsAxis=us-gaap_OperatingSegmentsMember', window );">Operating Segments [Member] | Ionis Core [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="top.Show.showAR( this, 'defref_us-gaap_SegmentReportingDisclosureOfEntitysReportableSegmentsAbstract', window );"><strong>Segment Information [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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">622,941<span></span>
</td>
<td class="nump">858,646<span></span>
</td>
<td class="nump">641,944<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_CostsAndExpenses', window );">Total operating expenses</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">563,647<span></span>
</td>
<td class="nump">523,207<span></span>
</td>
<td class="nump">380,212<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_OperatingIncomeLoss', window );">Income (loss) from operations</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">59,294<span></span>
</td>
<td class="nump">335,439<span></span>
</td>
<td class="nump">261,732<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_Assets', window );">Total assets</a></td>
<td class="nump">2,792,222<span></span>
</td>
<td class="nump">3,478,081<span></span>
</td>
<td class="nump">2,792,222<span></span>
</td>
<td class="nump">3,478,081<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_srt_ConsolidationItemsAxis=us-gaap_OperatingSegmentsMember', window );">Operating Segments [Member] | Ionis Core [Member] | 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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_SegmentReportingDisclosureOfEntitysReportableSegmentsAbstract', window );"><strong>Segment Information [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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">297,917<span></span>
</td>
<td class="nump">305,608<span></span>
</td>
<td class="nump">240,685<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_srt_ConsolidationItemsAxis=us-gaap_OperatingSegmentsMember', window );">Operating Segments [Member] | Ionis Core [Member] | SPINRAZA Royalties [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_SegmentReportingDisclosureOfEntitysReportableSegmentsAbstract', window );"><strong>Segment Information [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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">286,583<span></span>
</td>
<td class="nump">292,992<span></span>
</td>
<td class="nump">237,930<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_srt_ConsolidationItemsAxis=us-gaap_OperatingSegmentsMember', window );">Operating Segments [Member] | Ionis Core [Member] | Product Sales, 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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_SegmentReportingDisclosureOfEntitysReportableSegmentsAbstract', window );"><strong>Segment Information [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">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="top.Show.showAR( this, 'defref_srt_ConsolidationItemsAxis=us-gaap_OperatingSegmentsMember', window );">Operating Segments [Member] | Ionis Core [Member] | 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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_SegmentReportingDisclosureOfEntitysReportableSegmentsAbstract', window );"><strong>Segment Information [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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">11,334<span></span>
</td>
<td class="nump">12,616<span></span>
</td>
<td class="nump">2,755<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_srt_ConsolidationItemsAxis=us-gaap_OperatingSegmentsMember', window );">Operating Segments [Member] | Ionis Core [Member] | R&amp;D Revenue Under Collaborative 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>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_SegmentReportingDisclosureOfEntitysReportableSegmentsAbstract', window );"><strong>Segment Information [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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">325,024<span></span>
</td>
<td class="nump">553,038<span></span>
</td>
<td class="nump">401,259<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_srt_ConsolidationItemsAxis=us-gaap_OperatingSegmentsMember', window );">Operating Segments [Member] | Akcea Therapeutics [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="top.Show.showAR( this, 'defref_us-gaap_SegmentReportingDisclosureOfEntitysReportableSegmentsAbstract', window );"><strong>Segment Information [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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">152,320<span></span>
</td>
<td class="nump">488,543<span></span>
</td>
<td class="nump">64,867<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_CostsAndExpenses', window );">Total operating expenses</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">389,575<span></span>
</td>
<td class="nump">450,469<span></span>
</td>
<td class="nump">295,683<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_OperatingIncomeLoss', window );">Income (loss) from operations</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="num">(237,255)<span></span>
</td>
<td class="nump">38,074<span></span>
</td>
<td class="num">(230,816)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_Assets', window );">Total assets</a></td>
<td class="nump">435,824<span></span>
</td>
<td class="nump">599,250<span></span>
</td>
<td class="nump">435,824<span></span>
</td>
<td class="nump">599,250<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_srt_ConsolidationItemsAxis=us-gaap_OperatingSegmentsMember', window );">Operating Segments [Member] | Akcea Therapeutics [Member] | 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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_SegmentReportingDisclosureOfEntitysReportableSegmentsAbstract', window );"><strong>Segment Information [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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">69,999<span></span>
</td>
<td class="nump">52,425<span></span>
</td>
<td class="nump">14,237<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_srt_ConsolidationItemsAxis=us-gaap_OperatingSegmentsMember', window );">Operating Segments [Member] | Akcea Therapeutics [Member] | SPINRAZA Royalties [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_SegmentReportingDisclosureOfEntitysReportableSegmentsAbstract', window );"><strong>Segment Information [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">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="top.Show.showAR( this, 'defref_srt_ConsolidationItemsAxis=us-gaap_OperatingSegmentsMember', window );">Operating Segments [Member] | Akcea Therapeutics [Member] | Product Sales, 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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_SegmentReportingDisclosureOfEntitysReportableSegmentsAbstract', window );"><strong>Segment Information [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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">69,999<span></span>
</td>
<td class="nump">42,253<span></span>
</td>
<td class="nump">2,237<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_srt_ConsolidationItemsAxis=us-gaap_OperatingSegmentsMember', window );">Operating Segments [Member] | Akcea Therapeutics [Member] | 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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_SegmentReportingDisclosureOfEntitysReportableSegmentsAbstract', window );"><strong>Segment Information [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">10,172<span></span>
</td>
<td class="nump">12,000<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_srt_ConsolidationItemsAxis=us-gaap_OperatingSegmentsMember', window );">Operating Segments [Member] | Akcea Therapeutics [Member] | R&amp;D Revenue Under Collaborative 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>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_SegmentReportingDisclosureOfEntitysReportableSegmentsAbstract', window );"><strong>Segment Information [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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">82,321<span></span>
</td>
<td class="nump">436,118<span></span>
</td>
<td class="nump">50,630<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_srt_ConsolidationItemsAxis=us-gaap_IntersegmentEliminationMember', window );">Elimination of Intercompany Activity [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="top.Show.showAR( this, 'defref_us-gaap_SegmentReportingDisclosureOfEntitysReportableSegmentsAbstract', window );"><strong>Segment Information [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="num">(45,997)<span></span>
</td>
<td class="num">(224,590)<span></span>
</td>
<td class="num">(107,137)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_CostsAndExpenses', window );">Total operating expenses</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="num">(51,876)<span></span>
</td>
<td class="num">(216,960)<span></span>
</td>
<td class="num">(14,849)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_OperatingIncomeLoss', window );">Income (loss) from operations</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">5,879<span></span>
</td>
<td class="num">(7,630)<span></span>
</td>
<td class="num">(92,288)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_Assets', window );">Total assets</a></td>
<td class="num">$ (838,291)<span></span>
</td>
<td class="num">$ (844,219)<span></span>
</td>
<td class="num">(838,291)<span></span>
</td>
<td class="num">(844,219)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_srt_ConsolidationItemsAxis=us-gaap_IntersegmentEliminationMember', window );">Elimination of Intercompany Activity [Member] | 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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_SegmentReportingDisclosureOfEntitysReportableSegmentsAbstract', window );"><strong>Segment Information [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="num">(3,217)<span></span>
</td>
<td class="num">(5,583)<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="top.Show.showAR( this, 'defref_srt_ConsolidationItemsAxis=us-gaap_IntersegmentEliminationMember', window );">Elimination of Intercompany Activity [Member] | SPINRAZA Royalties [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_SegmentReportingDisclosureOfEntitysReportableSegmentsAbstract', window );"><strong>Segment Information [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">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="top.Show.showAR( this, 'defref_srt_ConsolidationItemsAxis=us-gaap_IntersegmentEliminationMember', window );">Elimination of Intercompany Activity [Member] | Product Sales, 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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_SegmentReportingDisclosureOfEntitysReportableSegmentsAbstract', window );"><strong>Segment Information [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">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="top.Show.showAR( this, 'defref_srt_ConsolidationItemsAxis=us-gaap_IntersegmentEliminationMember', window );">Elimination of Intercompany Activity [Member] | 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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_SegmentReportingDisclosureOfEntitysReportableSegmentsAbstract', window );"><strong>Segment Information [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="num">(3,217)<span></span>
</td>
<td class="num">(5,583)<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="top.Show.showAR( this, 'defref_srt_ConsolidationItemsAxis=us-gaap_IntersegmentEliminationMember', window );">Elimination of Intercompany Activity [Member] | R&amp;D Revenue Under Collaborative 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>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_SegmentReportingDisclosureOfEntitysReportableSegmentsAbstract', window );"><strong>Segment Information [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="num">$ (42,780)<span></span>
</td>
<td class="num">$ (219,007)<span></span>
</td>
<td class="num">$ (107,137)<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_Assets">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 942<br> -SubTopic 210<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-03(11))<br> -URI http://asc.fasb.org/extlink&amp;oid=120398452&amp;loc=d3e534808-122878<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 235<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.4-08(g)(1)(ii))<br> -URI http://asc.fasb.org/extlink&amp;oid=120395691&amp;loc=d3e23780-122690<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 825<br> -SubTopic 10<br> -Section 50<br> -Paragraph 28<br> -Subparagraph (f)<br> -URI http://asc.fasb.org/extlink&amp;oid=75031198&amp;loc=d3e14064-108612<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 810<br> -SubTopic 10<br> -Section 50<br> -Paragraph 3<br> -Subparagraph (bb)<br> -URI http://asc.fasb.org/extlink&amp;oid=121559654&amp;loc=d3e5710-111685<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 810<br> -SubTopic 10<br> -Section 45<br> -Paragraph 25<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=116870748&amp;loc=SL6758485-165988<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (d)<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e8933-108599<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 22<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e8736-108599<br><br>Reference 8: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 944<br> -SubTopic 210<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-03(a)(12))<br> -URI http://asc.fasb.org/extlink&amp;oid=120400017&amp;loc=d3e572229-122910<br><br>Reference 9: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 323<br> -SubTopic 10<br> -Section 50<br> -Paragraph 3<br> -Subparagraph (c)<br> -URI http://asc.fasb.org/extlink&amp;oid=114001798&amp;loc=d3e33918-111571<br><br>Reference 10: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 30<br> -Subparagraph (c)<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e8906-108599<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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_CostsAndExpenses">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.5-03)<br> -URI http://asc.fasb.org/extlink&amp;oid=120395209&amp;loc=SL114868664-224227<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>
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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>
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</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>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Number of segments reported by the entity. A reportable segment is a component of an entity for which there is an accounting requirement to report separate financial information on that component in the entity's financial statements.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 18<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e8672-108599<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_NumberOfReportableSegments</td>
</tr>
<tr>
<td 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>
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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_OperatingIncomeLoss">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 31<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e8924-108599<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 30<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e8906-108599<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (c)<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e8933-108599<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (f)<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e8933-108599<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 22<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e8736-108599<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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_RevenueFromContractWithCustomerExcludingAssessedTax">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 30<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e8906-108599<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 40<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e9031-108599<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 41<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e9038-108599<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e8933-108599<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e8933-108599<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=121604090&amp;loc=SL49130543-203045<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 22<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e8736-108599<br><br>Reference 8: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 22<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e8736-108599<br><br>Reference 9: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 42<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e9054-108599<br><br>Reference 10: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 50<br> -Paragraph 5<br> -URI http://asc.fasb.org/extlink&amp;oid=121604090&amp;loc=SL49130545-203045<br><br>Reference 11: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 924<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 11.L)<br> -URI http://asc.fasb.org/extlink&amp;oid=6472922&amp;loc=d3e499488-122856<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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_SegmentReportingAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_SegmentReportingAbstract</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>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>
</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> 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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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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>
</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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<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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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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<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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
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<td><strong> Period Type:</strong></td>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<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>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember</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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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_ConsolidationItemsAxis=us-gaap_OperatingSegmentsMember</td>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_StatementBusinessSegmentsAxis=ions_IonisCoreMember</td>
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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>na</td>
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<tr>
<td><strong> Balance Type:</strong></td>
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<tr>
<td><strong> Period Type:</strong></td>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_StatementBusinessSegmentsAxis=ions_AkceaTherapeuticsMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_StatementBusinessSegmentsAxis=ions_AkceaTherapeuticsMember</td>
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<tr>
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<td><strong> Period Type:</strong></td>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_srt_ConsolidationItemsAxis=us-gaap_IntersegmentEliminationMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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_ConsolidationItemsAxis=us-gaap_IntersegmentEliminationMember</td>
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<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<td>na</td>
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<td><strong> Balance Type:</strong></td>
<td></td>
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<td><strong> Period Type:</strong></td>
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<DOCUMENT>
<TYPE>XML
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<TEXT>
<html>
<head>
<title></title>
<link rel="stylesheet" type="text/css" href="report.css">
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<body>
<span style="display: none;">v3.20.4</span><table class="report" border="0" cellspacing="2" id="idm140142728101064">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Segment Information and Concentration of Business Risk, Contracts Receivable from Significant Partners (Details) - Partner<br></strong></div></th>
<th class="th" colspan="2">12 Months Ended</th>
</tr>
<tr>
<th class="th"><div>Dec. 31, 2020</div></th>
<th class="th"><div>Dec. 31, 2019</div></th>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_SignificantPartnersAbstract', window );"><strong>Significant Partners [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="top.Show.showAR( this, 'defref_ions_NumberOfSignificantPartners', window );">Number of significant partners</a></td>
<td class="nump">2<span></span>
</td>
<td class="nump">1<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ConcentrationRiskByBenchmarkAxis=us-gaap_AccountsReceivableMember', window );">Contracts Receivables [Member] | Credit Concentration [Member] | Significant Partners [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="top.Show.showAR( this, 'defref_ions_SignificantPartnersAbstract', window );"><strong>Significant Partners [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="top.Show.showAR( this, 'defref_us-gaap_ConcentrationRiskPercentage1', window );">Concentration percentage</a></td>
<td class="nump">99.50%<span></span>
</td>
<td class="nump">75.00%<span></span>
</td>
</tr>
</table>
<div style="display: none;">
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<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Represents the number of significant partners.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_SignificantPartnersAbstract</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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 42<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e9054-108599<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 275<br> -SubTopic 10<br> -Section 50<br> -Paragraph 18<br> -URI http://asc.fasb.org/extlink&amp;oid=99393423&amp;loc=d3e6351-108592<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 825<br> -SubTopic 10<br> -Section 50<br> -Paragraph 20<br> -URI http://asc.fasb.org/extlink&amp;oid=121572278&amp;loc=d3e13531-108611<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 825<br> -SubTopic 10<br> -Section 50<br> -Paragraph 21<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=121572278&amp;loc=d3e13537-108611<br><br>Reference 5: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 275<br> -SubTopic 10<br> -Section 50<br> -Paragraph 20<br> -URI http://asc.fasb.org/extlink&amp;oid=99393423&amp;loc=d3e6404-108592<br></p></div>
<a href="javascript:void(0);" onclick="top.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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<td><strong> Data Type:</strong></td>
<td>na</td>
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<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
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</tr>
</table></div>
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<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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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>
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<td><strong> Data Type:</strong></td>
<td>na</td>
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<td><strong> Balance Type:</strong></td>
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<td><strong> Period Type:</strong></td>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_srt_MajorCustomersAxis=ions_SignificantPartnersMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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_SignificantPartnersMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
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<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
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<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
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<DOCUMENT>
<TYPE>XML
<SEQUENCE>123
<FILENAME>R87.htm
<DESCRIPTION>IDEA: XBRL DOCUMENT
<TEXT>
<html>
<head>
<title></title>
<link rel="stylesheet" type="text/css" href="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;">v3.20.4</span><table class="report" border="0" cellspacing="2" id="idm140142732009016">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Employment Benefits (Details) - USD ($)<br></strong></div></th>
<th class="th" colspan="3">12 Months Ended</th>
</tr>
<tr>
<th class="th"><div>Dec. 31, 2020</div></th>
<th class="th"><div>Dec. 31, 2019</div></th>
<th class="th"><div>Dec. 31, 2018</div></th>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_GeneralDiscussionOfPensionAndOtherPostretirementBenefitsAbstract', window );"><strong>Employee Benefits [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_DefinedContributionPlanCostRecognized', window );">Matching contributions</a></td>
<td class="nump">$ 5,700,000<span></span>
</td>
<td class="nump">$ 6,400,000<span></span>
</td>
<td class="nump">$ 5,700,000<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_DefinedContributionPlanMaximumAnnualContributionsPerEmployeeAmount', window );">Employee contribution limit per calendar year</a></td>
<td class="nump">19,500<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="top.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>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_DefinedContributionPlanMaximumAnnualContributionsPerEmployeeAmount', window );">Employee contribution limit per calendar year</a></td>
<td class="nump">$ 26,000<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_us-gaap_DefinedContributionPlanCostRecognized">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of cost for defined contribution plan.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 715<br> -SubTopic 70<br> -Section 50<br> -Paragraph 1<br> -URI http://asc.fasb.org/extlink&amp;oid=49170846&amp;loc=d3e28014-114942<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DefinedContributionPlanCostRecognized</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
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<td><strong> Data Type:</strong></td>
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<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 border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DefinedContributionPlanMaximumAnnualContributionsPerEmployeeAmount">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DefinedContributionPlanMaximumAnnualContributionsPerEmployeeAmount</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<td><strong> Data Type:</strong></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></div>
</div></td></tr>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_GeneralDiscussionOfPensionAndOtherPostretirementBenefitsAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_GeneralDiscussionOfPensionAndOtherPostretirementBenefitsAbstract</td>
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<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>na</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="top.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>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<td><strong> Data Type:</strong></td>
<td>na</td>
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<td><strong> Balance Type:</strong></td>
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<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">srt_RangeAxis=srt_MaximumMember</td>
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<td></td>
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<td><strong> Data Type:</strong></td>
<td>na</td>
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<head>
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<span style="display: none;">v3.20.4</span><table class="report" border="0" cellspacing="2" id="idm140142725002440">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Fourth Quarter Financial Data (Unaudited) (Details) - USD ($)<br> $ / shares in Units, shares in Thousands, $ in Thousands</strong></div></th>
<th class="th" colspan="1">1 Months Ended</th>
<th class="th" colspan="1">2 Months Ended</th>
<th class="th" colspan="4">3 Months Ended</th>
<th class="th" colspan="3">12 Months Ended</th>
</tr>
<tr>
<th class="th"><div>Oct. 31, 2020</div></th>
<th class="th"><div>Dec. 31, 2020</div></th>
<th class="th" colspan="2"><div>Dec. 31, 2020</div></th>
<th class="th" colspan="2"><div>Dec. 31, 2019</div></th>
<th class="th"><div>Dec. 31, 2020</div></th>
<th class="th"><div>Dec. 31, 2019</div></th>
<th class="th"><div>Dec. 31, 2018</div></th>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_Revenues', window );">Revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 290,281<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">$ 493,680<span></span>
</td>
<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="top.Show.showAR( this, 'defref_us-gaap_CostsAndExpenses', window );">Operating expenses</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">312,945<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">233,028<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">$ 901,346<span></span>
</td>
<td class="nump">$ 756,716<span></span>
</td>
<td class="nump">$ 661,046<span></span>
</td>
</tr>
<tr class="rou">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_OperatingIncomeLoss', window );">Income (loss) from operations</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="num">(22,664)<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">260,652<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="num">(172,082)<span></span>
</td>
<td class="nump">365,883<span></span>
</td>
<td class="num">(61,372)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ProfitLoss', window );">Net income (loss)</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="num">(341,426)<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">203,957<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="num">(486,766)<span></span>
</td>
<td class="nump">303,262<span></span>
</td>
<td class="nump">214,985<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_NetIncomeLoss', window );">Net income (loss) attributable to Ionis Pharmaceuticals, Inc. common stockholders</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="num">$ (340,271)<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">$ 184,415<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="num">$ (451,286)<span></span>
</td>
<td class="nump">$ 294,146<span></span>
</td>
<td class="nump">$ 273,741<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_EarningsPerShareBasic', window );">Basic net income (loss) per share (in dollars per share)</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="num">$ (2.44)<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"><sup>[1],[2]</sup></td>
<td class="nump">$ 1.31<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"><sup>[1],[2]</sup></td>
<td class="num">$ (3.23)<span></span>
</td>
<td class="nump">$ 2.12<span></span>
</td>
<td class="nump">$ 2.09<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_EarningsPerShareDiluted', window );">Diluted net income (loss) per share (in dollars per share)</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="num">$ (2.44)<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"><sup>[2],[3]</sup></td>
<td class="nump">$ 1.28<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"><sup>[2],[3]</sup></td>
<td class="num">$ (3.23)<span></span>
</td>
<td class="nump">$ 2.08<span></span>
</td>
<td class="nump">$ 2.07<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_NetIncomeLossAvailableToCommonStockholdersDilutedAbstract', window );"><strong>Income (Numerator) [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_NetIncomeLossAvailableToCommonStockholdersBasic', window );">Income (loss) available to Ionis common stockholders</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="num">$ (340,272)<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">$ 183,795<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="num">$ (451,487)<span></span>
</td>
<td class="nump">$ 296,563<span></span>
</td>
<td class="nump">$ 276,868<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_NetIncomeLossAvailableToCommonStockholdersDiluted', window );">Net income available to Ionis common shareholders</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">$ 196,485<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 296,563<span></span>
</td>
<td class="nump">$ 276,868<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_WeightedAverageNumberOfSharesOutstandingDilutedDisclosureItemsAbstract', window );"><strong>Shares (Denominator) [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_WeightedAverageNumberOfSharesOutstandingBasic', window );">Shares used in computing basic net income (loss) per share (in shares)</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">139,956<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">140,583<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">139,612<span></span>
</td>
<td class="nump">139,998<span></span>
</td>
<td class="nump">132,320<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_WeightedAverageNumberDilutedSharesOutstandingAdjustmentAbstract', window );"><strong>Effect of Diluted Securities [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_IncrementalCommonSharesAttributableToEmployeeStockPurchasePlan', window );">Shares issuable related to our ESPP (in shares)</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">18<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">18<span></span>
</td>
<td class="nump">6<span></span>
</td>
</tr>
<tr class="rou">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding', window );">Shares used in computing diluted net income per share (in shares)</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">153,303<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">139,612<span></span>
</td>
<td class="nump">142,872<span></span>
</td>
<td class="nump">134,056<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.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="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="top.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="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_DebtInstrumentInterestRateStatedPercentage', window );">Interest rate on convertible senior notes</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">0.125%<span></span>
</td>
<td class="nump">0.125%<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">0.125%<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">0.125%<span></span>
</td>
<td class="nump">0.125%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_NetIncomeLossAvailableToCommonStockholdersDilutedAbstract', window );"><strong>Income (Numerator) [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_DilutiveSecuritiesEffectOnBasicEarningsPerShareOther', window );">Shares issuable related to our convertible notes</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">$ 644<span></span>
</td>
<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="top.Show.showAR( this, 'defref_us-gaap_WeightedAverageNumberDilutedSharesOutstandingAdjustmentAbstract', window );"><strong>Effect of Diluted Securities [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_IncrementalCommonSharesAttributableToConversionOfDebtSecurities', window );">Shares issuable related to our convertible notes</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">860<span></span>
</td>
<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="top.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="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="top.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="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_DebtInstrumentInterestRateStatedPercentage', window );">Interest rate on convertible senior notes</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">1.00%<span></span>
</td>
<td class="nump">1.00%<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">1.00%<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">1.00%<span></span>
</td>
<td class="nump">1.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_NetIncomeLossAvailableToCommonStockholdersDilutedAbstract', window );"><strong>Income (Numerator) [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_DilutiveSecuritiesEffectOnBasicEarningsPerShareOther', window );">Shares issuable related to our convertible notes</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">$ 12,046<span></span>
</td>
<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="top.Show.showAR( this, 'defref_us-gaap_WeightedAverageNumberDilutedSharesOutstandingAdjustmentAbstract', window );"><strong>Effect of Diluted Securities [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_IncrementalCommonSharesAttributableToConversionOfDebtSecurities', window );">Shares issuable related to our convertible notes</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">9,527<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AwardTypeAxis=us-gaap_EmployeeStockOptionMember', window );">Stock Options [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_WeightedAverageNumberDilutedSharesOutstandingAdjustmentAbstract', window );"><strong>Effect of Diluted Securities [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_IncrementalCommonSharesAttributableToShareBasedPaymentArrangements', window );">Shares issuable related to stock-based compensation (in shares)</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">1,467<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">2,090<span></span>
</td>
<td class="nump">1,216<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AwardTypeAxis=us-gaap_RestrictedStockMember', window );">Restricted Stock Awards [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_WeightedAverageNumberDilutedSharesOutstandingAdjustmentAbstract', window );"><strong>Effect of Diluted Securities [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_IncrementalCommonSharesAttributableToShareBasedPaymentArrangements', window );">Shares issuable related to stock-based compensation (in shares)</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">848<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">766<span></span>
</td>
<td class="nump">514<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_StatementBusinessSegmentsAxis=ions_IonisCoreMember', window );">Ionis [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="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="top.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="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_NetIncomeLoss', window );">Net income (loss) attributable to Ionis Pharmaceuticals, Inc. common stockholders</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="num">$ (250,682)<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">$ 121,552<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="num">$ (253,725)<span></span>
</td>
<td class="nump">$ 262,490<span></span>
</td>
<td class="nump">$ 440,806<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_srt_OwnershipAxis=ions_AkceaTherapeuticsIncMember', window );">Akcea [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="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="top.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="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_NetIncomeLoss', window );">Net income (loss) attributable to Ionis Pharmaceuticals, Inc. common stockholders</a></td>
<td class="num">$ (3,603)<span></span>
</td>
<td class="num">$ (85,987)<span></span>
</td>
<td class="num">$ (89,590)<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">$ 62,243<span></span>
</td>
<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="top.Show.showAR( this, 'defref_us-gaap_EarningsPerShareBasic', window );">Basic net income (loss) per share (in dollars per share)</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="num">$ (0.05)<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">$ 0.87<span></span>
</td>
<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 custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_WeightedAverageNumberOfSharesOwnedInSubsidiary', window );">Weighted average shares owned in Akcea (in shares)</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">77,095<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">71,342<span></span>
</td>
<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="10"></td></tr>
<tr><td colspan="10"><table class="outerFootnotes" width="100%">
<tr class="outerFootnote">
<td style="vertical-align: top; width: 12pt;" valign="top">[1]</td>
<td style="vertical-align: top;" valign="top">As discussed in Note 1, Organization and Significant Accounting Policies, we compute basic net income (loss) per share by dividing the total net income (loss) attributable to our common stockholders by our weighted-average number of common shares outstanding during the period. Our basic net income (loss) per share calculation for each of the fourth quarters in 2020 and 2019 considered our net income (loss) for Ionis on a stand-alone basis plus our share of Akcea&#8217;s net loss for the period. To calculate the portion of Akcea&#8217;s net loss attributable to our ownership, we multiplied Akcea&#8217;s loss per share by the weighted average shares we owned in Akcea during the period. As a result of this calculation, our total net income (loss) available to Ionis common stockholders for the calculation of net income (loss) per share is different than net income (loss) attributable to Ionis Pharmaceuticals, Inc. common stockholders in the consolidated statements of operations.</td>
</tr>
<tr class="outerFootnote">
<td style="vertical-align: top; width: 12pt;" valign="top">[2]</td>
<td style="vertical-align: top;" valign="top">We compute net income (loss) per share independently for each quarter during the year.</td>
</tr>
<tr class="outerFootnote">
<td style="vertical-align: top; width: 12pt;" valign="top">[3]</td>
<td style="vertical-align: top;" valign="top">We had net income available to Ionis common stockholders for the fourth quarter of 2019. As a result, we computed diluted net income per share using the weighted-average number of common shares and dilutive common equivalent shares outstanding during the period</td>
</tr>
</table></td></tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_IncrementalCommonSharesAttributableToEmployeeStockPurchasePlan">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Additional shares included in the calculation of diluted EPS as a result of the potentially dilutive effect of shares issuable related to employee stock purchase plan.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_IncrementalCommonSharesAttributableToEmployeeStockPurchasePlan</td>
</tr>
<tr>
<td style="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_WeightedAverageNumberOfSharesOwnedInSubsidiary">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Number of shares owned in the subsidiary during the reporting period determined by relating the portion of time within a reporting period that shares have been owned to the total time in that period.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_WeightedAverageNumberOfSharesOwnedInSubsidiary</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:sharesItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_CostsAndExpenses">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.5-03)<br> -URI http://asc.fasb.org/extlink&amp;oid=120395209&amp;loc=SL114868664-224227<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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_DebtInstrumentInterestRateStatedPercentage">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02.22(a)(1))<br> -URI http://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>num: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_DilutiveSecuritiesEffectOnBasicEarningsPerShareOther">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of increase (decrease) to net income used for calculating diluted earnings per share (EPS), resulting from the assumed exercise of dilutive convertible securities excluding adjustments related to ESOP convertible preferred stock, stock options, and restrictive stock units.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DilutiveSecuritiesEffectOnBasicEarningsPerShareOther</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>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_EarningsPerShareBasic">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 250<br> -SubTopic 10<br> -Section 50<br> -Paragraph 3<br> -URI http://asc.fasb.org/extlink&amp;oid=109234566&amp;loc=d3e22583-107794<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 250<br> -SubTopic 10<br> -Section 50<br> -Paragraph 11<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=109234566&amp;loc=d3e22694-107794<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 45<br> -Paragraph 10<br> -URI http://asc.fasb.org/extlink&amp;oid=121326447&amp;loc=d3e1448-109256<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 250<br> -SubTopic 10<br> -Section 50<br> -Paragraph 4<br> -URI http://asc.fasb.org/extlink&amp;oid=109234566&amp;loc=d3e22595-107794<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 250<br> -SubTopic 10<br> -Section 50<br> -Paragraph 11<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=109234566&amp;loc=d3e22694-107794<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 45<br> -Paragraph 7<br> -URI http://asc.fasb.org/extlink&amp;oid=121326447&amp;loc=d3e1337-109256<br><br>Reference 7: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 55<br> -Paragraph 52<br> -URI http://asc.fasb.org/extlink&amp;oid=120380238&amp;loc=d3e4984-109258<br><br>Reference 8: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 944<br> -SubTopic 220<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-04(23))<br> -URI http://asc.fasb.org/extlink&amp;oid=120400993&amp;loc=SL114874131-224263<br><br>Reference 9: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 55<br> -Paragraph 15<br> -URI http://asc.fasb.org/extlink&amp;oid=120380238&amp;loc=d3e3842-109258<br><br>Reference 10: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 250<br> -SubTopic 10<br> -Section 50<br> -Paragraph 7<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=109234566&amp;loc=d3e22644-107794<br><br>Reference 11: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=6371337&amp;loc=d3e3550-109257<br><br>Reference 12: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.5-03(25))<br> -URI http://asc.fasb.org/extlink&amp;oid=120395209&amp;loc=SL114868664-224227<br><br>Reference 13: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 45<br> -Paragraph 2<br> -URI http://asc.fasb.org/extlink&amp;oid=121326447&amp;loc=d3e1252-109256<br><br>Reference 14: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 45<br> -Paragraph 60B<br> -Subparagraph (d)<br> -URI http://asc.fasb.org/extlink&amp;oid=121326447&amp;loc=SL5780133-109256<br><br>Reference 15: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 942<br> -SubTopic 220<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-04(27))<br> -URI http://asc.fasb.org/extlink&amp;oid=120399700&amp;loc=SL114874048-224260<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>num: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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 55<br> -Paragraph 52<br> -URI http://asc.fasb.org/extlink&amp;oid=120380238&amp;loc=d3e4984-109258<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 250<br> -SubTopic 10<br> -Section 50<br> -Paragraph 7<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=109234566&amp;loc=d3e22644-107794<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 55<br> -Paragraph 15<br> -URI http://asc.fasb.org/extlink&amp;oid=120380238&amp;loc=d3e3842-109258<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 45<br> -Paragraph 2<br> -URI http://asc.fasb.org/extlink&amp;oid=121326447&amp;loc=d3e1252-109256<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 250<br> -SubTopic 10<br> -Section 50<br> -Paragraph 11<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=109234566&amp;loc=d3e22694-107794<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 250<br> -SubTopic 10<br> -Section 50<br> -Paragraph 4<br> -URI http://asc.fasb.org/extlink&amp;oid=109234566&amp;loc=d3e22595-107794<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 250<br> -SubTopic 10<br> -Section 50<br> -Paragraph 3<br> -URI http://asc.fasb.org/extlink&amp;oid=109234566&amp;loc=d3e22583-107794<br><br>Reference 8: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 45<br> -Paragraph 60B<br> -Subparagraph (d)<br> -URI http://asc.fasb.org/extlink&amp;oid=121326447&amp;loc=SL5780133-109256<br><br>Reference 9: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 942<br> -SubTopic 220<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-04(27))<br> -URI http://asc.fasb.org/extlink&amp;oid=120399700&amp;loc=SL114874048-224260<br><br>Reference 10: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=6371337&amp;loc=d3e3550-109257<br><br>Reference 11: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 944<br> -SubTopic 220<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-04(23))<br> -URI http://asc.fasb.org/extlink&amp;oid=120400993&amp;loc=SL114874131-224263<br><br>Reference 12: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 250<br> -SubTopic 10<br> -Section 50<br> -Paragraph 11<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=109234566&amp;loc=d3e22694-107794<br><br>Reference 13: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 45<br> -Paragraph 7<br> -URI http://asc.fasb.org/extlink&amp;oid=121326447&amp;loc=d3e1337-109256<br><br>Reference 14: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.5-03(25))<br> -URI http://asc.fasb.org/extlink&amp;oid=120395209&amp;loc=SL114868664-224227<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>num:perShareItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_IncrementalCommonSharesAttributableToConversionOfDebtSecurities">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Additional shares included in the calculation of diluted EPS as a result of the potentially dilutive effect of convertible debt securities using the if-converted method.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 45<br> -Paragraph 40<br> -Subparagraph (c)<br> -URI http://asc.fasb.org/extlink&amp;oid=121326447&amp;loc=d3e1930-109256<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 45<br> -Paragraph 42<br> -URI http://asc.fasb.org/extlink&amp;oid=121326447&amp;loc=d3e2029-109256<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=6371337&amp;loc=d3e3550-109257<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_IncrementalCommonSharesAttributableToConversionOfDebtSecurities</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:sharesItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_IncrementalCommonSharesAttributableToShareBasedPaymentArrangements">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Additional shares included in the calculation of diluted EPS as a result of the potentially dilutive effect of share based payment arrangements using the treasury stock method.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 45<br> -Paragraph 22<br> -URI http://asc.fasb.org/extlink&amp;oid=121326447&amp;loc=d3e1707-109256<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=6371337&amp;loc=d3e3550-109257<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 45<br> -Paragraph 28A<br> -URI http://asc.fasb.org/extlink&amp;oid=121326447&amp;loc=d3e1500-109256<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 45<br> -Paragraph 23<br> -Subparagraph (c)<br> -URI http://asc.fasb.org/extlink&amp;oid=121326447&amp;loc=d3e1757-109256<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_IncrementalCommonSharesAttributableToShareBasedPaymentArrangements</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:sharesItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_NetIncomeLoss">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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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-SubTopic 10<br> -Section 50<br> -Paragraph 30<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e8906-108599<br><br>Reference 18: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 250<br> -SubTopic 10<br> -Section 50<br> -Paragraph 3<br> -URI http://asc.fasb.org/extlink&amp;oid=109234566&amp;loc=d3e22583-107794<br><br>Reference 19: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 235<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.4-08(g)(1)(ii))<br> -URI http://asc.fasb.org/extlink&amp;oid=120395691&amp;loc=d3e23780-122690<br><br>Reference 20: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 45<br> -Paragraph 60B<br> -Subparagraph (a)<br> -URI 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<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_NetIncomeLoss</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_NetIncomeLossAvailableToCommonStockholdersBasic">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount, after deduction of tax, noncontrolling interests, dividends on preferred stock and participating securities; of income (loss) available to common shareholders.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 250<br> -SubTopic 10<br> -Section 50<br> -Paragraph 4<br> -URI http://asc.fasb.org/extlink&amp;oid=109234566&amp;loc=d3e22595-107794<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 45<br> -Paragraph 10<br> -URI http://asc.fasb.org/extlink&amp;oid=121326447&amp;loc=d3e1448-109256<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 250<br> -SubTopic 10<br> -Section 50<br> -Paragraph 11<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=109234566&amp;loc=d3e22694-107794<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 45<br> -Paragraph 11<br> -URI http://asc.fasb.org/extlink&amp;oid=121326447&amp;loc=d3e1377-109256<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=6371337&amp;loc=d3e3550-109257<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 22<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e8736-108599<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 250<br> -SubTopic 10<br> -Section 50<br> -Paragraph 11<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=109234566&amp;loc=d3e22694-107794<br><br>Reference 8: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 45<br> -Paragraph 60B<br> -Subparagraph (c)<br> -URI http://asc.fasb.org/extlink&amp;oid=121326447&amp;loc=SL5780133-109256<br><br>Reference 9: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (f)<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e8933-108599<br><br>Reference 10: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 31<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e8924-108599<br><br>Reference 11: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 30<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e8906-108599<br><br>Reference 12: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 250<br> -SubTopic 10<br> -Section 50<br> -Paragraph 3<br> -URI http://asc.fasb.org/extlink&amp;oid=109234566&amp;loc=d3e22583-107794<br><br>Reference 13: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (c)<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e8933-108599<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_NetIncomeLossAvailableToCommonStockholdersBasic</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_NetIncomeLossAvailableToCommonStockholdersDiluted">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount, after deduction of tax, noncontrolling interests, dividends on preferred stock and participating securities, and addition from assumption of issuance of common shares for dilutive potential common shares; of income (loss) available to common shareholders.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 45<br> -Paragraph 60B<br> -Subparagraph (c)<br> -URI http://asc.fasb.org/extlink&amp;oid=121326447&amp;loc=SL5780133-109256<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=6371337&amp;loc=d3e3550-109257<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 45<br> -Paragraph 16<br> -URI http://asc.fasb.org/extlink&amp;oid=121326447&amp;loc=d3e1505-109256<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_NetIncomeLossAvailableToCommonStockholdersDiluted</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<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_NetIncomeLossAvailableToCommonStockholdersDilutedAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_NetIncomeLossAvailableToCommonStockholdersDilutedAbstract</td>
</tr>
<tr>
<td style="padding-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_OperatingIncomeLoss">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 31<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e8924-108599<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 30<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e8906-108599<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (c)<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e8933-108599<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (f)<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e8933-108599<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 22<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e8736-108599<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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_ProfitLoss">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The consolidated profit or loss for the period, net of income taxes, including the portion attributable to the noncontrolling interest.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 235<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.4-08(g)(1)(ii))<br> -URI http://asc.fasb.org/extlink&amp;oid=120395691&amp;loc=d3e23780-122690<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section 45<br> -Paragraph 1A<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=121641772&amp;loc=SL7669619-108580<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 205<br> -SubTopic 20<br> -Section 50<br> -Paragraph 7<br> -URI 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-Name Accounting Standards Codification<br> -Topic 810<br> -SubTopic 10<br> -Section 45<br> -Paragraph 19<br> -URI http://asc.fasb.org/extlink&amp;oid=108774443&amp;loc=SL4569616-111683<br><br>Reference 18: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 323<br> -SubTopic 10<br> -Section 50<br> -Paragraph 3<br> -Subparagraph (c)<br> -URI http://asc.fasb.org/extlink&amp;oid=114001798&amp;loc=d3e33918-111571<br><br>Reference 19: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (f)<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e8933-108599<br><br>Reference 20: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 810<br> -SubTopic 10<br> -Section 55<br> -Paragraph 4K<br> -URI 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<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ProfitLoss</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_Revenues">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 22<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e8736-108599<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 323<br> -SubTopic 10<br> -Section 50<br> -Paragraph 3<br> -Subparagraph (c)<br> -URI http://asc.fasb.org/extlink&amp;oid=114001798&amp;loc=d3e33918-111571<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 825<br> -SubTopic 10<br> -Section 50<br> -Paragraph 28<br> -Subparagraph (f)<br> -URI http://asc.fasb.org/extlink&amp;oid=75031198&amp;loc=d3e14064-108612<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e8933-108599<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e8933-108599<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 22<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e8736-108599<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 40<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e9031-108599<br><br>Reference 8: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 30<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e8906-108599<br><br>Reference 9: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 41<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e9038-108599<br><br>Reference 10: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 42<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e9054-108599<br><br>Reference 11: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 235<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.4-08(g)(1)(ii))<br> -URI http://asc.fasb.org/extlink&amp;oid=120395691&amp;loc=d3e23780-122690<br><br>Reference 12: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 942<br> -SubTopic 235<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-05(b)(2))<br> -URI http://asc.fasb.org/extlink&amp;oid=120399901&amp;loc=d3e537907-122884<br><br>Reference 13: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.5-03(1))<br> -URI http://asc.fasb.org/extlink&amp;oid=120395209&amp;loc=SL114868664-224227<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_Revenues</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_SelectedQuarterlyFinancialInformationAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_SelectedQuarterlyFinancialInformationAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_WeightedAverageNumberDilutedSharesOutstandingAdjustmentAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_WeightedAverageNumberDilutedSharesOutstandingAdjustmentAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=6371337&amp;loc=d3e3550-109257<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 45<br> -Paragraph 16<br> -URI http://asc.fasb.org/extlink&amp;oid=121326447&amp;loc=d3e1505-109256<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=6371337&amp;loc=d3e3550-109257<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 45<br> -Paragraph 10<br> -URI http://asc.fasb.org/extlink&amp;oid=121326447&amp;loc=d3e1448-109256<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_WeightedAverageNumberOfSharesOutstandingBasic</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:sharesItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_WeightedAverageNumberOfSharesOutstandingDilutedDisclosureItemsAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_WeightedAverageNumberOfSharesOutstandingDilutedDisclosureItemsAbstract</td>
</tr>
<tr>
<td style="padding-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_DebtInstrumentAxis=ions_ConvertibleSeniorNotes0125PercentMember">
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end
</TEXT>
</DOCUMENT>
</SEC-DOCUMENT>
